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Abstract
In a case-control study, the relationship between a family history of cancer of the breast, ovary, colon, uterus or prostate and the risk of breast cancer was investigated. The data consisted of family histories from 495 breast cancer cases and 785 controls aged 20-56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in the families of the subjects affected. This relationship increased linearly with both the degree of kinship of the affected relatives and with their number. The risk of breast cancer associated with other types of cancer in the family was not significantly different from unity.
... To date, there is little understanding of the needs of women who have a family history of breast cancer. Evidence suggests that these women may not carry out early detection practices at rates different from the general population of women (Hill & Shugg 1989, Vogel et al. 1990, Andrieu et al. 1991, Wellisch et al. 1991, Richardson et al. 1993, Thirlaway & Fallow®eld 1993, Drossaert et al. 1996, Benedict et al. 1997, Brain et al. 1999. Women with a family history of breast cancer have reported feelings of vulnerability to breast cancer (Beckett et al. 1991, Kash et al. 1995, Herbert-Croteau et al. 1997. ...
Information and support needs of women with primary relatives with breast cancer: development of the Information and Support Needs Questionnaire
Aims of the study. The aim was to develop and pilot test a newly developed measure, The Information and Support Needs Questionnaire (ISNQ), for use with women with primary relatives with breast cancer.
Background/rationale. Breast cancer is a major risk to the health of women in the United Kingdom (UK). Increasingly, research is documenting women’s needs for information and support, particularly at the time of diagnosis. However, to date there is little understanding of the information and support needs of women who have a family history of breast cancer. Contributing to the dearth of understanding of female relatives’ needs is the lack of valid and reliable instruments for use in descriptive and intervention research with this population.
Design/methods. The ISNQ and survey items documenting family history, sources of information and support for breast cancer risk, breast self-care practices, and other variables were pilot tested for the acceptability of the measures, appropriateness of the data collection methods, initial psychometric properties of the ISNQ, and time and financial costs of administration. Data were collected from 39 women living in the North-west of England who had primary relatives with breast cancer using mailed questionnaires and follow-up telephone interviews.
Findings. The items on the ISNQ were reported to be clear, acceptable to women and to yield relevant data. The psychometric properties of the new measure were satisfactory with a high reliability coefficient alpha. Descriptive findings indicate that women had moderate to high needs for information and support, but reported that these needs were not well met.
Conclusions. The results of this pilot are guiding the development of a larger study in which the information and support needs of women with a family history of breast cancer are explored.
... An association between prostate cancer and uterine cancer in relatives of women with breast cancer has also been reported (Thiessen, 1974). However, other studies have failed to find any association between prostate cancer and breast cancer (Isaacs et al., 1995;Andreieu et al., 1991). Furthermore, Isaacs et al. (1995) reported no major aggregation of other malignant diseases in prostate-cancer families, apart from a small increased risk for tumours in the central nervous system. ...
There is a familial aggregation of prostate cancer, and 5 to 10% of all prostate cancers are estimated to be inherited in an autosomal-dominant mode. A population-based cohort study was performed in order to study familial prostate cancer and associated malignancies. A nation-wide register cohort study was conducted using an unselected study population. The cohort of 5,595 sons and 5,089 daughters of Swedish men found to have prostate cancer between 1959 and 1963 was identified. All types of cancer reported between 1958 and 1992 in this cohort were identified through linkage to the Swedish Cancer Registry. The expected number of different cancers was calculated using incidence rates obtained from the Registry. A highly significant increased overall standardized incidence ratio (SIR) of 1.65 (95% CI, 1.49-1.83) was obtained for prostate cancer, with 370 observed cases compared with 224 expected prostate cancers. The SIR was 3.18 among cases 45 to 49 years old at diagnosis, with the risk gradually decreasing to a SIR of 1.45 among cases over 80 years of age. Among sons and daughters with a father whose prostate cancer was diagnosed at an early age (<70 years), an increased risk for colorectal cancer SIR 1.48 (1.10-1.95) was observed. No significant difference in cancer risk for other sites was observed among the daughters and sons of men with prostate cancer. This cohort study confirms earlier studies that a positive family history of prostate cancer is an important risk factor for developing this disease. Though increased risk was found for all ages, it was more pronounced in younger men. Since no other malignancy was significantly associated with prostate cancer, it is most likely that familial prostate cancer is "site-specific".
... Cerhan et al. (29) found that for probands with prostate cancer, the prostate cancer risk to their relatives increased if a mother or sister had breast or ovarian cancer. Two other studies failed to find association of breast and prostate cancer (66,67). ...
Prostate cancer is the most frequent cancer among men in most developed countries, yet little is known about its causes. Older age, African ancestry and a positive family history of prostate cancer have long been recognized as important risk factors. The evidence that genetics probably plays a critical role is based on a variety of study designs, including case-control, cohort, twin and family-based, all of which are reviewed in detail. The search for prostate cancer susceptibility genes by linkage studies offered early hope that finding genes would be as 'easy' as finding genes for breast cancer and colon cancer susceptibilities. However, this hope has been dampened by the difficulty of replicating promising regions of linkage. This review provides updates on recent developments, and a broad view of the disparate findings from different linkage studies. Early linkage results have provided targeted candidate regions for prostate cancer susceptibility loci, including HPC1 on chromosome 1q23-25, PCAP on chromosome 1q42-43, CAPB on chromosome 1p36, linkage to chromosome 8p22-23, HPC2 on chromosome 17p, HPC20 on chromosome 20q13, and HPCX on chromosome Xq27-28. These linkage findings lead to refined mapping and mutation screening of several strong candidate genes, including ELAC2, RNASEL and MSR1. Up to now, a total of 10 genome-wide linkage scans for prostate cancer susceptibility have been completed, and are reviewed. Furthermore, recent findings that Gleason's grade, a measure of aggressiveness of prostate cancer, is linked to several genomic regions are reviewed. Finally, the roles of environmental and dietary risk factors, and common genetic polymorphisms of genes likely to play a role in common forms of prostate cancer, are briefly discussed within in the context of searching for genes that influence prostate cancer risk.
Gynecologic and Urologic Pathology - edited by Maria Rosaria Raspollini
Colorectal cancer is the third most common cancer worldwide (after breast and cervix in women and lung and stomach in men); it accounts for approximately 9% of all cancers1. Incidence varies approximately 20-fold around the world2,3. Highest rates are seen largely in the developed world — western Europe, North America, Australasia — with age-adjusted (world standard) incidence rates of 25 to 35 per 100 000 in the late 1980s. It is notable that rates in northern Italy (>30 per 100 000 for males) are now higher than in England and Wales (<20 per 100 000). The formerly low rates in Japan have now risen to a level comparable to those in England and Wales. The lowest rates are seen in India (1– 3 per 100 000)3.
Recent research makes it probable that there is a hereditary form of prostate cancer. By identifying prostate cancer cases in the Swedish twin registry it was possible to show a pronounced difference in proband concordance rates and correlation of liability between monozygotic and dizygotic twin pairs, which indicates strongly that genetic factors are important for prostate cancer. In a nation-wide register cohort study it was found that the risk for prostate cancer was approximately two times higher among sons to prostate cancer patients when compared to Swedish men in general. By linkage analyses at least two loci for putative prostate cancer genes have been identified, one on chromosome 1 (1q24-25) and one on the X-chromosome (Xq27-28). Before genetic testing becomes available it was suggested that men with the familiar aggregation of prostate cancer should be evaluated with a PSA test on a regular basis.
The goal of this study was to explore and describe the meaning of the risk experience in women with primary relatives with breast cancer (mother, sister, mother and sister, and mother and other primary relative). An exploratory, descriptive study was conducted using semistructured, in-depth, tape-recorded interviews as the primary data collection method. Fifty-five women formed the sample. Data were analyzed using qualitative analysis procedures. Women's descriptions of their experiences revealed that their perceptions of being "at risk" and their self-care practices developed over time. Developing a personal view of risk occurred in three phases: living the breast cancer experience of the relative(s), developing a risk perception, and putting risk in its place. The phases and their related components are described in detail.
From 1977 to 1986, 264 women with stage I or II breast cancer and positive breast cancer family histories were treated with conservative surgery, axillary dissection, and irradiation. The records of these cases were reviewed and compared to those of 517 women with stage I or II breast cancer and negative breast cancer family histories who were treated similarly during the same time period. Patients with a negative family history were more likely to present with positive axillary lymph nodes than patients whose history was positive (33% vs. 26.5%, p = 0.054). There were no statistically significant differences found between the family history positive and family history negative women in terms of 5 and 10 year actuarial overall survival (5 yr: 91% vs. 90%, 10 yr: 86% vs. 82%) or relapse-free survival (5 yr: 76% vs. 76%, 10 yr: 64% vs. 61 %). Breast recurrence rates were likewise not significantly different for the two groups of patients (5 yr: 6% vs. 9%, 10 yr: 17% vs. 18%). A separate analysis restricted to lymph node-positive patients revealed no significant differences in survival between the family history positive and family history negative groups. It thus appears that women with early stage breast cancer who have a family history of the disease can be treated with breast-conserving surgery and definitive irradiation with the same excellent results as seen in women without such a family history.
Background. Conservative surgery (CS) and radiation therapy (RT) as an alternative to mastectomy is controversial in patients with two or more lesions in the same breast. The authors reviewed their experience with CS and RT in the management of patients with synchronous ipsilateral breast cancer (SIBC).Methods. Of 1060 patients treated with CS and RT at the authors' facilities before December 1988, 13 (1.2%) presented with SIBC. All lesions were identified macroscopically and confirmed microscopically as carcinoma. After excision, patients were treated with radiation to the breast for a median tumor bed dose of 65 Gy, and regional lymphatics were treated as clinically indicated to a median dose of 48 Gy. These cases were retrospectively reviewed.Results. As of February 1992, with a median follow-up of 71 months, the 5-year actuarial survival rate of the 13 patients was 81%. Three of the 13 (23%) had an ipsilateral breast recurrence, resulting in a 72-month actuarial breast recurrence rate of 25%, compared with a rate of 12% in our singular lesion population. Two of these patients remain alive, no evidence of disease at 135 and 93 months after diagnosis. The third patient had chest wall progression and died with metastatic disease at 64 months. Invasive lobular histology and three separate lesions were identified in two of the three patients with subsequent local recurrence.Conclusions. The local recurrence rate in conservatively treated patients with SIBC is greater than that seen in patients with single lesions, but because of the small sample size, significant conclusions are not possible. Although the data are limited on this subject, these results support consideration of CS and RT as an option in the management of selected patients who favor a breast conservation management approach. Cancer 1993; 72:137–42.
The aim of this study was to describe the information and support needs of women who have primary relatives with breast cancer. The Information and Support Needs Questionnaire (ISNQ) was developed and revised from previous qualitative and pilot studies. The ISNQ addressed concepts of the importance of, and the degree to which, 29 information and support needs related to breast cancer had been met. The study sample consisted of 261 community-residing women who had mothers, sisters, or a mother and sister(s) with breast cancer. Data were collected using a mailed survey. In addition to the ISNQ, additional items addressed family and health history, breast self-care practices, perception of the impact of the relative's breast cancer and other variables. Also included were established and well-validated measures of anxiety and depression. The findings document women's priority information and support needs. The information need most frequently identified as very important was information about personal risk of breast cancer. Other highly rated needs addressed risk factors for breast cancer and early detection measures. Generally, the women perceived that their information and support needs were not well met. These findings illuminate needs of women for more information and support when they have close family relatives with breast cancer and opportunities for primary care providers to assist women in addressing their needs.
The aggregation of colon, endometrial, ovarian, and possibly breast cancers in families has been described as a “cancer family syndrome” (now called Lynch syndrome II). To determine if the familial clustering of these malignancies was more common in women with cancer than without, we analyzed data from the Iowa Women's Health Study (IWHS), a population-based sample of 41,837 women aged 55–69 years. Self-reported information was collected on history of colon, uterine, ovarian, and breast cancers in female first-degree relatives. A family history of cancer of the breast (odds ratio [OR] = 1.4), colon (OR = 1.3), and uterus (OR = 1.3), but not ovary (OR = 1.2), was significantly more common among women with a personal history of any of these four cancers (all P < 0.05); the pattern of the ORs suggested strongly that the clustering tended to be site-specific. Age-adjusted relative risks (RR) of incident colon cancer over 5 years of follow-up (N = 237) were calculated with regard to family history. Colon cancer incidence was increased among women with a family history of breast (RR = l.3), uterine (RR = 1.4), colon (RR = l.5), and ovarian (RR = 1.3) cancers, although none of the risk estimates achieved statistical significance. RR was, however, significantly related to the number of different cancer sites reported among family members (Ptrend = 0.008). These data on a representative sample of postmenopausal women suggest that family histories of colon, breast, uterine, and ovarian cancers are associated with an increased risk of cancer at the same site, but provide little support for the hypothesis that Lynch syndrome II is a non-random occurrence. © 1993 Wiley-Liss, Inc.
Previous studies have provided conflicting results concerning the effects of a family history of prostate and other cancers on breast cancer risks.
Three groups of families were studied to determine the effects of a family history of prostate cancer on breast cancer risks. Also considered were the effects of a family history of melanoma, colon, lung, ovarian, and endometrial cancers. Included were 422 first-degree female relatives of 114 patients with bilateral breast cancer, 320 first-degree relatives of 88 male patients with breast cancer, and 633 relatives of 186 unselected female patients. For estimating relative risks, observed numbers of breast cancers in relatives were compared with expected numbers based on population incidence data. Multiple logistic-regression also provided odds ratios of relatives affected with breast cancer.
A family history of prostate cancer increased the breast cancer risks in each of the groups, compared with families without prostate cancer. Ovarian cancer in a family increased the breast cancer risks only in the bilateral breast cancer group, and endometrial cancer increased the risks in the bilateral and unselected groups. These increases in risk appeared to be the consequence of families with multiple cancers, including those with hereditary breast-ovarian cancers and the cancer family syndrome. A family history of melanoma, lung, or colon cancer did not increase breast cancer risks.
A family history of prostate cancer, as well as endometrial and ovarian cancer, significantly increases the risk of breast cancer.
Both genetic and exogenous factors are probably important in prostate cancer development, but the specific causes remain poorly understood. An increasing body of evidence now suggests that high animal fat or red meat intake appears to increase risk for this cancer. Some studies indicate that high intake of retinol may be deleterious, but β-carotene may lower risk, although these data are inconsistent. Carotenoids other than β-carotene are only now being examined in relation to prostate cancer risk. Ongoing epidemiologic studies may help clarify the relation between diet and prostate cancer. Most studies indicate that men who have had a vasectomy have an increased risk for prostate cancer to develop, although whether this association is causal is unknown. Familial factors are important, particularly at younger ages. Overall, about 9% of cases may be attributed directly to a family history of prostate cancer, although this may be as high as 43% among men younger than 55 years. No occupational factor has been confirmed as a risk factor. Some evidence suggests that occupational exposure to cadmium and some aspect of farming may increase risk moderately, but these would account for a small proportion of the total cases. Dietary factors appear to hold the most promise for primary prevention, but the precise factors and mechanisms need to be better understood. Cancer 1995; 75:1766–77.
Lifetime probabilities of developing breast cancer were calculated for first-degree female relatives of three groups of breast cancer patients: 114 with bilateral cancer, 186 unselected, and 88 males. The patients were classified according to whether they had a family history of prostate, endometrial, or ovarian cancer, or no family history of these cancers. In families of unselected female and male patients with no family history of prostate, endometrial, or ovarian cancer, the lifetime probability of developing breast cancer was 11.4%. The risk increased slightly to 13.5% when these other cancers may or may not have present (i.e., they were ignored, which is the usual method in computing risks) and increased further to 25.5% when prostate, endometrial, or ovarian cancer was present in the family. In families of patients with bilateral cancer the respective risks were 10.9%, 17.3%, and 34.4%. A family history of prostate cancer increased lifetime risk consistently in each of the groups, to 29.0% in the unselected and male groups and to 38.2% in the bilateral group. Endometrial cancer increased risk only in the bilateral group (to 41.8%) as did ovarian cancer (to 54.6%). Increased risk of breast cancer with a family history of endometrial or ovarian cancer appeared to be influenced by families with hereditary breast-ovarian cancer or the cancer family syndrome. The results indicate that prostate cancer, and endometrial and ovarian cancers in some families, can significantly increase breast cancer risk and should be taken into account when counseling women about their breast cancer risk.
Prostate cancer risk has been associated with a family history of the disease. A two- to three-fold increase in risk has been observed in several studies. Details concerning modification of this risk by age, type of familial history of prostate cancer, and possible involvement of history of cancer at other sites have been less well documented. This case-control study of 1,271 prostate cancer patients and 1,909 control subjects admitted to Roswell Park Cancer Institute in Buffalo, NY, found age-adjusted increased risk associated with reporting a history of prostate cancer in a father (RR = 2.3, 95% Cl 1.4−3.3) or brother (RR = 2.5, 95% Cl 1.6−3.9). Subjects with both a father and brother affected had a 6.5-fold (95% Cl 1.4–30.5) increased risk of prostate cancer. Greater risk were observed at younger ages of diagnosis. Risks associated with reporting a father or a brother affected were not significantly elevated for patients over age 70 at diagnosis. No significant differences in patients reporting histories of cancer other than prostate cancer were observed regardless of relationship, age at diagnosis, or type of cancer examined. These observations from a large cancer patient population may be useful when making recommendations for cost-effective prostate cancer screening and for directing investigators to the potentially most informative subjects.
Background
tory of colon cancer has been shown to be related to the risk of developing colon cancer. e impact that a comprehensive family history of colon or other cancers has on the risk of colon cancer has not been thoroughly studied.
Purpose
The purpose of this study was to assess the risk of developing colon cancer associated with having a family history of colon, rectal, breast, ovarian, en-dometrial, or prostate cancer.
Methods
A case-control study was conducted using data from the Utah Population Database. Case patients had first primary colon cancers (n = 2543). Three control subjects per case were individually matched to case patients on year of birth, place of birth, marital status, and sex.
Results
Those case patients with the highest familial standardized incidence ratio were at an increased risk of developing colon cancer (for men, odds ratio [OR] = 2.51 and 95% confidence interval [CI] = 1.88−3.29; for women, OR = 2.90 and 95% CI = 2.17-3.82). A second- or third-degree relative with colon cancer increased risk from 25% to 52%. Risk associated with family history was greater in those patients diagnosed before age 50 (for men, OR = 3.61 and for women, OR = 7.18) than in those diagnosed at 50 or more years of age (for men, OR = 2.44 and for women, OR = 2.73). The risk associated with a family history of colon cancer was greatest for the distal segment of the colon. Women were at an increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.59; 95% CI = 1.25−2.03), uterine (OR = 1.50; 95% CI = 0.99−2.26), ovarian (OR = 1.63; 95% CI = 1.41−1.89), or prostate (OR = 1.49; 95% CI = 1.21−1.82) cancer; men were at increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.30; 95% CI = 1.02−1.66), uterine (OR = 1.96; 95% CI = 1.34−2.87), or ovarian (OR = 1.59; 95% CI = 0.90−2.81) cancer.
Conclusions
dings support previous observations that people with a family history of colon cancer are at increased risk of colon cancer. Those with a second- or third-degree relative with colon cancer or a first-degree relative with breast, ovarian, uterine, or prostate cancer also have an increased risk of developing colon cancer.
Implications
These data support the recommendations that individuals who have a first-degree, and possibly a second- or third-degree, relative with colon cancer should have regular screening for colon cancer. [J Natl Cancer Inst 86:1618-1626, 1994
Previous studies have provided conflicting results concerning the familial effect of male breast cancer on breast cancer risks in female relatives.
We studied breast cancer risks in first-degree relatives of male patients and compared them with relatives of female patients.
Our study included 88 consecutively ascertained male patients and 320 of their first-degree relatives as well as 186 consecutively ascertained female patients and 633 of their first-degree relatives. Observed numbers of breast cancers in relatives were compared with the expected number derived from the Connecticut Tumor Registry. Multiple logistic regression analysis was also performed.
Relatives of male patients exhibited a significant twofold increased risk when compared with expected rates and no difference in risk when compared with that of relatives of female patients. Prostate cancer in the family of a male patient resulted in a significant fourfold increased breast cancer risk compared with a risk of 1.4 in families with no history of prostate cancer. A family history of lung cancer, colon cancer, or melanoma had no effect on increasing risks of breast cancer.
The familial effect of male breast cancer is the same as that of female breast cancer.
Any estimates of breast cancer risk provided to individuals should also consider the occurrence of prostate cancer in the family, since prostate cancer appears capable of at least doubling the underlying twofold risk.
It is estimated that there will be more than 244,000 new prostate cancer cases diagnosed and that more than 40,000 men will die of this disease during 1995. Evidence exists for a hereditary predisposition to prostate cancer, but the proportion of cases attributable to the inheritance of a specific gene or genes is not large. Some hereditary cancer syndromes involve more than one tumor site, and some studies have reported a familial association between prostate cancer and other cancers. The presence of other cancers in prostate cancer families may indicate a specific type of hereditary predisposition.
We studied families that were selected because of the presence of prostate cancer to determine whether hereditary prostate cancer is associated with cancers at other sites and possibly with other heritable cancer syndromes.
Data from two distinct study populations were studied retrospectively. The first population consisted of 690 case patients undergoing radical prostatectomy who were not selected for family history of prostate cancer and 640 control subjects who were the spouses or female companions of the case patients. The second population consisted of 75 multiplex families (i.e., families with multiple cases of prostate cancer) referred because they fulfilled the criteria for hereditary prostate cancer. A comparison between case and control populations for the occurrence of 14 aggregated groups of cancer was performed. Data were analyzed using Poisson regression, and relative risks (RRs) and their 95% confidence intervals (CIs) were calculated.
Brothers and fathers of prostate cancer probands have a statistically significant higher risk of prostate cancer than the male first-degree relatives of control subjects (RR = 1.76; 95% CI = 1.28-2.43). Therefore, the risk for prostate cancer is 76% higher among first-degree relatives of prostate cancer patients compared with first-degree relatives of control subjects. This higher risk was not modified by an occurrence of breast cancer in the pedigree. Also, a statistically significant higher risk was found for tumors of the central nervous system in hereditary families (RR = 3.02; 95% CI = 1.08-8.41). Statistically significant higher risks of cancer at other major sites, such as breast, ovary, or endometrium were not observed in these families.
Even among families that were specifically selected because of the presence of prostate cancer, risks for cancer at other sites appeared not to be increased. Therefore, hereditary prostate cancer appears to be a relatively site-specific disease, and it does not seem to be a part of other hereditary cancer syndromes.
Previous studies have suggested that cancers of the breast and prostate cluster in families and that the presence of both diseases in a family may be associated with increased risk of breast cancer.
Our purpose was to evaluate whether 1) prostate cancer aggregates in families with postmenopausal breast cancer, 2) families with cancers of the breast and prostate are the same ones as families with cancers of the breast and ovary, and 3) a family history of prostate cancer is associated with increased risk of postmenopausal breast cancer.
We analyzed data from a large prospective cohort study of Iowa women that were (at baseline) aged 55-69 years in 1986. At the third follow-up survey in 1992, self-reported data on family history of breast, ovarian, and prostate cancers in parents and siblings were provided by 30,883 women. Additional information was collected to ascertain whether the age-of-onset of breast cancer in mothers or sisters was before or after the age of 45 years. Cancer occurrence was documented using the State Health Registry of Iowa.
History of prostate cancer in their father or a brother was reported by 3384 (11.0%) of the women, and a total of 4090 women (13.2%) reported breast cancer in their mother or a sister. A positive family history of both cancers was reported by 556 women, significantly (two-sided P < .001) greater than the 457 women expected if the family histories were independent. The aggregation of breast, prostate, and ovarian cancers was reported by 22 participants, greater than the 2.7 expected (two-sided P < .0001). During 6 years of follow-up, 578 breast cancers were identified in the cohort at risk. Compared with women without a family history of either cancer, women with a family history of breast cancer had a relative risk (RR) of 1.37 (95% confidence interval [CI] = 1.06-1.79) if the affected relative had onset after the age of 45 years, and an RR of 1.71 (95% CI = 1.13-2.61) if the affected relative had onset at or before the age of 45. A family history of prostate cancer in the absence of a family history of breast cancer was associated with an RR of 1.19 (95% CI = .90-1.56). However, a family history of both breast and prostate cancers was associated with RRs of 2.06 (95% CI = 1.23-3.45) and 2.35 (95% CI = .97-5.67) for breast cancer onset in relatives of greater than 45 and less than or equal to 45 years, respectively.
These observations are concordant with recent reports that suggest a shared familial risk (inherited or environmental) for these hormone-dependent malignancies.
In a case-control study of 495 breast cancer patients and 785 controls between 20 and 56 years of age, the risk of breast cancer associated with a family history of breast cancer was studied according to age and reproductive factors. The familial risk of breast cancer was not significantly modified by age at onset, age at menarche, number of children, age at first full-term pregnancy, menstrual cycle length or age at menopause. However, the familial risk significantly increased with the number of abortions (p < 0.05) and seemed to decrease after a natural menopause (p = 0.08). These results suggest that a familial predisposition to breast cancer exerts the same influence during the first six decades of life, except maybe when there are isolated or repeated events such as abortions or artificially imposed menopause, in which case the risk is apparently greater.
In this article, the role of information, support, and communication in promoting adaptation to the risk of breast cancer is reported. These variables emerged from an in-depth study of women at risk for breast cancer because of breast cancer in one or more of their primary (first degree) relatives. Fifty-five women with mothers, sisters, mother and sister, or mother and another primary relative were interviewed using in-depth semi-structured, tape-recorded interviews. After transcription, data were analyzed using qualitative analysis procedures. A three-phase process of adaptation to the risk of breast cancer was uncovered, which was subsequently validated with two study participants. Information, support, and communication emerged as important factors in facilitating the adjustment of women throughout the three phases of the process: as women "lived" the breast cancer experience of their relative; as they developed a perception of their personal risk for breast cancer; and finally as they put the risk of breast cancer "in its place." Despite the importance of information and support, most women had difficulty meeting these needs. Also, communication patterns both within the family and with health professionals were generally not helpful for these women. Issues related to the ill relative as "manager" of cancer-related information, the "ownership style" of the woman at risk, and the accessibility and availability of resources influenced women's adaptation to feelings of risk. Women's needs for information, support, and communication and facilitating factors are described in detail, and recommendations for clinical practice and research offered.
There are recent data to suggest that risk factors for breast cancer may differ according to whether the tumor expresses detectable levels of the estrogen receptor (ER) and progesterone receptor (PR). While a family history of breast cancer is one of the most consistent predictors of the disease, we recently reported a modest inverse association with ER+PR- tumors. However, the definition of a family history of cancer did not consider second-degree relatives or cancer sites that may be etiologically related. The current report presents additional data analysis from the Iowa Women's Health Study, a prospective population-based cohort study conducted among 41,837 postmenopausal women. At baseline in 1986, respondents provided information on family history of cancers of the breast, ovaries, or uterus/endometrium in their mothers, sisters, daughters, maternal and paternal grandmothers, and maternal and paternal aunts. Data on family history of prostate cancer in fathers and brothers and age at onset of breast cancer in mothers and sisters were collected in 1992. Cohort members were followed for cancer incidence through the statewide tumor registry. After 7 years and more than 235,000 person-years of follow-up, 939 incident cases of breast cancer were identified. Information was obtained from the tumor registry on ER (+/-) and PR (+/-) status for 610 cases (65.0%). A family history of breast cancer in first-degree relatives was associated with increased risk (relative risk [PR] = 1.4; 95% confidence interval [CI]: 1.1-1.6) for all receptor-defined subtypes of breast cancer except ER+PR- tumors (RR = 0.7; 95% CI: 0.3-1.4). These results were unchanged when data on second-degree relatives were included. When the onset of breast cancer in relatives occurred at or before the age of 45 years, increased risks were evident only for ER-PR+ and ER-PR- tumors (RR = 2.3 and 3.3, respectively). Conversely, when relatives were affected with breast cancer after the age of 45 years, increased risks were most apparent for ER+PR+ and ER-PR+ tumors (RR = 1.3 and 3.2, respectively). A family history of prostate cancer in first-degree relatives was associated with a 1.2-fold increased risk of breast cancer (95% CI: 0.98-1.50), largely a reflection of the association with ER-PR- tumors (RR = 1.5; 95% CI: 0.8-3.0). The small numbers of cases in some categories and the corresponding wide CIs preclude definitive conclusions, but these data are at least suggestive that joint stratification of breast tumors on ER and PR status may be useful in partitioning breast cancer families into more homogeneous subsets.
Breast and colon cancer are among the most common cancers in the developed world. Several epidemiological studies suggest that the occurrence of one of these two cancers in a woman may predispose to the development of the other. The occurrence of both forms of cancer in the same woman may be because of chance or common susceptibility. In order to determine how frequently double primary cancers have a hereditary basis, we conducted a registry based study at a single Montreal hospital. Cancer rates in first degree relatives of patients with multiple primaries were compared with provincial age standardised incidence rates and relative risks (RRs) were estimated. In first degree relatives under 45 there was a total of 15 cancers observed, compared with 3.70 expected, giving an RR of 4.05 (95% CI: 2.27-6.68). The RR for colon cancer was significantly increased among male relatives. For relatives less than 45 years old at diagnosis, the RR for colon cancer was 66.7 (95% CI: 13.8-195) (three cases observed, 0.045 expected). For all ages the RR was 5.02 (95% CI: 2.04-10.5). The RR for breast cancer was 5.92 (95% CI: 1.91-13.8) for female relatives under 45 (five cases observed, 0.845 expected) and 2.14 (95% CI: 1.07-3.83) for breast cancer at any age. These results suggest that there may be genes that predispose to both breast and colon cancer in certain people.
The purpose of this review is to examine the implications of recent trends in prostate cancer incidence and mortality and to consider recent progress of epidemiological research on this disease. The incidence and mortality rates for prostate cancer are changing throughout the world at an accelerating pace. Much of the increase in incidence is related to changes in detection technology, but increases in mortality rates suggest other factors are involved. Recent research has focused on race-related difference, diet and related lifestyle exposures, the aetiologic significance of vasectomy and, patterns of familial aggregation. Continued monitoring of trends in incidence and mortality will be important as prostate cancer becomes a greater public health burden worldwide. Epidemiological research has identified several possible risk factors which may be useful for prostate cancer prevention and targeting high-risk individuals for early detection intervention. Additional research may confirm and refine understanding of prostate cancer aetiology.
In this article the authors review factors determining risk for the development of colorectal cancer (CC) and their modification. Emphasis is placed on understanding the difference between average risk and high risk individuals. Risk factors including genetics, diet, environment, and coexistent diseases are discussed. The data regarding modification of risk via dietary, pharmaceutical, and prophylactic endoscopic and surgical interventions are reviewed.
A family history of prostate cancer has been associated with prostate cancer risk in most prior studies, and more limited data suggest that a family history of breast cancer may also be important; however, there are no data from a population-based cohort study of prostate cancer incidence that adjusts for major confounders. We conducted follow-up through 1995 on 1557 men, ages 40-86 years, who were randomly selected (81% response rate) as cancer-free controls for a population-based case-control study conducted in Iowa from 1987-1989. Family history of cancer in parents and siblings was obtained using a mailed questionnaire. Incident cancers and deaths were ascertained through linkages to state and national databases; 101 incident cases of prostate cancer were identified. At baseline, 4.6% of the cohort reported a family history of prostate cancer in a brother or father, and this was positively associated with prostate cancer risk after adjustment for age [relative risk (RR) = 3.2; 95% confidence interval (CI), 1.8-5.7] or after multivariate adjustment for age, alcohol, and dietary factors (RR = 3.7; 95% CI, 1.9-7.2). Risk was greater if a brother had prostate cancer (RR = 4.5; 95% CI, 2.1-9.7) than if a father had prostate cancer (RR = 2.3; 95% CI, 1.0-5.3). Also at baseline, 9.6% of the cohort had a family history of breast and/or ovarian cancer in a mother or sister, and this was positively associated with prostate cancer risk (age-adjusted RR = 1.7; 95% CI, 1.0-3.0; multivariate RR = 1.7; 95% CI, 0.9-3.2). Men with a family history of both prostate and breast/ovarian cancer were also at increased risk of prostate cancer (RR = 5.8; 95% CI, 2.4-14). There was no association with a family history of colon cancer. Exclusion of well-differentiated, localized tumors did not alter these findings. These data from an incidence study confirm that a family history of prostate cancer is a strong prostate cancer risk factor after adjustment for dietary and other risk factors, and suggest that selection and recall bias have not had an important influence on most case-control study results. These data also support the idea that a family history of breast cancer may also be a prostate cancer risk factor.
This study investigates the incidence of cancer in isolate populations. Thorough anthropological research over the past 3 decades has established island populations in Middle Dalmatia, Croatia, as outstanding examples of genetic isolates. The number of cancer cases on 5 islands (Brac, Hvar, Korcula, Vis, and Lastovo) over a 20-year period (1971-1990) has been extracted from the data of the Croatian Cancer Registry. The population of coastal Dalmatia, characterized by similar environmental factors but a different population genetic structure, was used as a control population. The leading hypothesis was that, if there were genes or gene complexes (especially with recessive inheritance) responsible for genetic susceptibility to certain types of cancer, then the incidence of those cancer types should be greater in reproductively isolated island populations than in a control population because of increased manifestation of such genes or gene complexes caused by inbreeding. Furthermore, the cancer incidence should increase along with greater reproductive isolation (i.e., greater geographic distance of the islands from the mainland). After adjusting the data for sex and age, I confirmed the hypothesis: Island populations have greater total cancer incidence than the control population for both sexes. The excess incidence on the islands shows an almost linear correlation with geographic distance from the mainland. The cancer sites primarily responsible for the excess incidence are bladder cancer in males, and breast, ovarian, brain, and large bowel cancer in females, predominantly in the younger age groups.
Recent research makes it probable that there is a hereditary form of prostate cancer. By identifying prostate cancer cases in the Swedish twin registry it was possible to show a pronounced difference in proband concordance rates and correlation of liability between monozygotic and dizygotic twin pairs, which indicates strongly that genetic factors are important for prostate cancer. In a nation-wide register cohort study it was found that the risk for prostate cancer was approximately two times higher among sons to prostate cancer patients when compared to Swedish men in general. By linkage analyses at least two loci for putative prostate cancer genes have been identified, one on chromosome 1 (1q24-25) and one on the X-chromosome (Xq27-28). Before genetic testing becomes available it was suggested that men with the familiar aggregation of prostate cancer should be evaluated with a PSA test on a regular basis.
Few studies examining familial clustering of breast and prostate cancer (PC) have focused on a clearly defined high-risk population with epidemiologic risk factors. We conducted a cohort study of prostate cancer among a subset of 426 families ascertained through female breast cancer probands. Three groups of males were included: 804 relatives in 60 families with four or more breast or ovarian cancers, 536 marry-ins in these high-risk families, and 484 relatives in 81 families where only the proband had breast cancer. A total of 118 prostate cancers were reported. The rate of prostate cancer among blood relatives in high-risk families was significantly lower than among marry-ins (RR = 0.6, 95% C.I.: 0.4-0.9). The rate of prostate cancer among blood relatives in low-risk families was not significantly different from the rate among marry-ins (RR = 0.8, 95% C.I.: 0.5-1.2). These results provide little evidence that male relatives in high-risk breast cancer families are at increased risk of prostate cancer.
The aim of this study was to describe the information and support needs of women who have primary relatives with breast cancer. The Information and Support Needs Questionnaire (ISNQ) was developed and revised from previous qualitative and pilot studies. The ISNQ addressed concepts of the importance of, and the degree to which, 29 information and support needs related to breast cancer had been met. The study sample consisted of 261 community-residing women who had mothers, sisters, or a mother and sister(s) with breast cancer. Data were collected using a mailed survey. In addition to the ISNQ, additional items addressed family and health history, breast self-care practices, perception of the impact of the relative's breast cancer and other variables. Also included were established and well-validated measures of anxiety and depression. The findings document women's priority information and support needs. The information need most frequently identified as very important was information about personal risk of breast cancer. Other highly rated needs addressed risk factors for breast cancer and early detection measures. Generally, the women perceived that their information and support needs were not well met. These findings illuminate needs of women for more information and support when they have close family relatives with breast cancer and opportunities for primary care providers to assist women in addressing their needs.
In order to assess the prognostic value of family history (FH) of malignancies in patients afflicted with breast cancer (BC), we examined FH and histopathologic characteristics of 542 Iranian primary BC patients. Cases with distant metastasis at the time of diagnosis were excluded. Mean age of the studied population was 49 and the most common presenting stage was stage IIA followed by stage IIB. Data on a total of 6089 relatives (1st to 4th generations with the assumption of probands as the 3rd generation) were gathered. FH of BC and other malignancies (OM) was positive in 29 and 54% of cases, respectively. The most common OM's were gastric (67), lung (52) and uterus (47) cancers. We found that a FH of BC does not have any significant correlation with proven prognostic factors but a history of BC among relatives at or before the age of 36 is associated with more aggressive tumours. On the other hand, although FH of OM was associated with an older age of the probands (which is generally associated with a favourable prognosis), tumours of the cases with FH of OM had higher grades, lymphatic invasion being detected more frequently. Also we noted that the younger the age of the relatives diagnosed with cancer, the higher the stage of the probands themselves. All together our study indicates the possibility of a relation between FH of BC and OM, and histopathologic characteristics of the probands' tumours which would put forward FH as a prognostic factor rather than a simple risk factor in BC.
Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies.
The relationship of family history of cancer of the breast, colon/rectum, cervix, endometrium, lung, and thyroid to the risk of epithelial ovarian cancer was investigated in a large population-based case-control study. The data consisted of family histories from 493 epithelial ovarian cancer cases and 2,465 controls aged 20–54 years. After controlling for potential confounders, risk for epithelial ovarian cancer was found to be significantly elevated among women reporting breast cancer and colo/rectal cancer in a first-degree relative. Adjusted odds ratios were 1.5 (95% CI = 1.1-2.1) and 1.9 (95% CI = 1.1-3.3), respectively. None of the remaining four types of cancer was found to be statistically associated with the risk of epithelial ovarian cancer. However, when histologic subtypes of epithelial ovarian cancer were considered, a family history of breast cancer was found to be associated with an elevated risk of endometrioid ovarian cancer (odds ratio = 2.3; 95% CI = 1.1-4.7), as was a family history of endometrial cancer (odds ratio = 2.7; 95% CI = 1.0-6.9). The results are considered in the context of other studies of familial patterns of cancer and are compared with published findings concerning the occurrence of multiple primary cancers in the same individual. The findings indicate that further study is warranted regarding possible genetic relationships between epithelial ovarian cancer and cancers arising in other organs.
In 1976, we designed an original questionnaire, consisting of 111 questions, directed at the epidemiology of prostatic disease. A case-control study by matched-pair analysis was conducted on 100 controls matched for age within 1 year and for residence in the same prefecture. Patients with prostatic cancer were distinguished from the general population of men by the following characteristics: 1) belonging to middle or lower socioeconomical class, 2) marriage at a young age and a long married life, 3) precocity, 4) vigorous sexual life followed by a fall-off of sexuality in later life, and 5) Western food habits. Based on analysis of results obtained in this case-control study, a high-risk group for prostatic cancer was outlined.
PIGAS is an interactive statistical database management system whose main assets include logical data checking, data entry for meaningful variables only, three different types of missing value codes, non-rectangular data structure and user interfaces with BMDP, GLIM or specifically written FORTRAN programs.The structure of the PIGAS language is the same as one passes from one phase of a research study to another, whether it be data updating, checking or analysis, thus requiring only a minimum amount of initiation in its use. It is particularly appealing since data verification is completely specified through variable names as they appear on the questionnaire. Instructions given in how to fill in a questionnaire can thus be directly incorporated in the data checking process, thus ensuring a good quality data base.
The relationship between the risk of breast cancer and oral contraceptive use was investigated in a case-control study conducted
in France between 1983 and 1987 in five public hospitals. Some 464 cases aged 25 to 56 years and 542 matched controls were
interviewed about their history of the use of oral contraceptives (OC).
Results are given for the entire population and for the subgroup of 358 and 379 premenopausal cases and controls. The multivariate
relative risk estimate, for ever use, was 1.5 (p<0.01) in the whole group as well as in the premenopausal subgroup (p<0.02).
However, there was no evidence that the effect varied appreciably according to duration of use, age at first use, use before
first full-term pregnancy (FFTP) and time since first or last use. The risk was not altered for any particular brand of OC.
We conclude that, because of the widespread attention given to the relationship between OC use and breast cancer, information
bias might be responsible for part of the excess in risk observed among OC ever users.
The possibility of a genetic relationship between ovarian, breast, and endometrial cancer was investigated in data from a large multicenter, population-based, case-control study, the Cancer and Steroid Hormone Study conducted by the Centers for Disease Control (CDC). Age-adjusted relative risks (RRs) for mothers and sisters of 493 ovarian cancer cases, 895 breast cancer cases, and 143 endometrial cancer cases versus 4,754 controls were calculated. Significantly elevated age-adjusted RRs were found for ovarian cancer (RR = 2.8; 95% confidence interval [CI] = 1.6-4.9) and breast cancer (RR = 1.6; 95% CI = 1.1-2.1) among relatives of ovarian cancer probands and for breast cancer (RR = 2.1; 95% CI = 1.7-2.5) and ovarian cancer (RR = 1.7; 95% CI = 1.0-2.0) among relatives of breast cancer probands. Relatives of endometrial cancer probands had an elevated RR for endometrial cancer only (RR = 2.7; 95% CI = 1.6-4.8). The genetic relationship between ovarian, breast, and endometrial cancer was tested using a multivariate polygenic threshold model developed by Smith (1976), which was modified to accommodate three classes of probands. Estimates of heritability for ovarian, breast, and endometrial cancer were 40%, 56%, and 52%, respectively. There was a significant genetic correlation between ovarian and breast cancer (R12 = .484). Evidence for significant genetic overlap between endometrial cancer and either ovarian or breast cancer was not found. These results suggest the existence of a familial breast/ovarian cancer syndrome. Endometrial cancer, while heritable, appears to be genetically unrelated.
A relationship between breast and colonic cancer has been suggested so we looked at the incidence of colonic carcinoma in the relatives of familial and sporadic breast cancer patients. We found that there is an increased incidence of colonic cancer in the relatives of familial breast cancer patients as compared with the relatives of sporadic breast cancer patients. This risk was higher in men than women (P less than or equal to 0.05). The relatives of familial breast cancer patients are a high risk group for developing colonic carcinoma, and would benefit from colonic screening.
The main results of segregation analysis aimed at identifying a major genetic factor involved in susceptibility to breast cancer are reviewed. They show that the existence of a single major gene is not sufficient to explain the distribution of the disease observed in the families concerned and suggest that the genetic inheritance involved is heterogeneous and complex. Heterogeneity has been explored in various studies according to epidemiological criteria. From these analyses, genetically homogeneous subgroups emerged (for instance families with breast cancer only or with affected males). The study of such homogeneous subgroups might help to better locate the susceptibility gene(s) on the chromosome map by analysis of genetic linkage using different markers. The results of segregation analysis depend on how epidemiological factors are taken into account. It is of major importance that epidemiological data on the proband (i.e., the individual prompting selection of a family) as well as on the members of his/her family are taken into consideration to improve understanding of the complexity of breast cancer transmission.
Using data from 5489 cancer patients and 2647 patients without cancer we investigated whether parental age at the birth of the patient or the patient's rank within his sibship was related to the risk of cancer during adulthood. An increase of 10 years in maternal age was associated with an increase of 24% for the incidence of breast cancer (odds ratio = 1.24%; 95% CI = 1.09-1.41); the corresponding increase for paternal age was 19% (odds ratio = 1.19; 95% CI = 1.07-1.33). There was some evidence that the age of each parent may make an independent contribution to the risk of breast cancer. For certain types of genito-urinary cancers, the risk was higher when the parents were relatively young at the birth of the patient. These cancers included tumors arising in the prostate (odds ratios = 0.71 and 0.55 for maternal and paternal ages, respectively), testis (odds ratios = 0.57 and 0.52), penis (odds ratios = 0.37 and 0.45), kidney (odds ratios = 0.66 and 0.60), and bladder (odds ratio = 0.79 and 0.85). The associations for cancer of the prostate and bladder were stronger among patients who were diagnosed at a relatively young age. No statistically significant effects were found for birth order relative to adult cancers. The authors conclude that environmental factors that affect the parents or that operate in the perinatal period may have stronger influences on the incidence of adult cancers than have been previously recognized.
Genetic analysis of human breast cancer, as with many common diseases, raises several problems including sampling strategies, genetic heterogeneity, and gene-environment interactions. A reanalysis of 200 Danish breast cancer pedigrees, under the unified mixed model, was conducted to investigate more specifically these three points. We found that use of different sampling schemes leads to similar conclusions: familial transmission of breast cancer in this whole Danish sample cannot be accounted for by the Mendelian segregation of a dominant gene. Homogeneity tests, based on an a priori subdivision of the sample, were all nonsignificant under a given genetic model. However, it was possible to isolate a particular subgroup of pedigrees displaying only breast cancer, which was compatible with the segregation of a dominant gene. We have also shown that correct specification of a liability indicator according to epidemiological factors is of major importance to detect a major effect under the mixed model. Our results emphasize the need to design family studies including various types of information in the probands and family members to permit some progress in the understanding of complex diseases.
We investigated the segregation pattern of breast cancer in families with bilateral breast cancer, classifying families with respect to menopausal status (premenopausal versus postmenopausal) and the interval between diagnosis of the two primary tumors in the probands. Probands were "synchronous" if both primaries were diagnosed within 1 year; "asynchronous" if the interval was at least 2 years. Results for four complex segregation analyses are here presented; the findings support heterogeneity in the transmission of breast cancer. In the asynchronous premenopausal-cases-only analysis, a dominant Mendelian gene can explain the breast cancer pattern. A recessive gene is sufficient to describe the breast cancer distribution in the synchronous premenopausal-cases-only analysis. The synchronous all-cases and the asynchronous all-cases analyses add postmenopausal cases of breast cancer to the premenopausal ones, considering any case to be affected. In the asynchronous all-cases analysis, neither the single-locus model nor the mixed model (that is, a major locus plus other factors, genetic and/or cultural) without generation differences in heritability can be rejected by the unrestricted mixed model with generation differences in heritability. For the synchronous all-cases analysis, a mixed model with generation differences in heritability is necessary to explain the breast cancer transmission. Potential sources of error and possible interpretations are discussed.
Epidemiologic data were studied and found to be incompatible with the horizontal transmission of a human breast cancer virus through milk. Regardless of the patient's age at diagnosis of breast cancer, no evidence of an increased risk associated with breast feeding was found. In addition, increased familial risk of breast cancer occurred in both paternal and maternal lines. The familial aggregation of the disease seemed related to an altered state of estrogen excretion or metabolism; the mothers of breast cancer patients had the delayed age at first delivery and at menopause characteristics of the patients. A decreased risk of breast cancer was associated with hormone administration at natural menopause.
The mammary gland is one part of an integrated genital organ system. The various parts of this system have distinctive shared biological and pathologic characteristics. Because of the frequent association of mammary, uterine, and ovarian cancer in the same individual, it is hypothesized that some common etiologic factor exists which might also have a familial expression in other parts of this genital organ system. Based upon this, the familial incidence and distribution of all malignancies for a group of 145 breast cancer patients were determined and compared to that of 139 randomized control patients. Significantly higher incidences of only uterine, prostatic, and breast cancer were found among both maternal and paternal relatives of the breast cancer patients.
A group of women was identified whose risk for breast cancer was 47-to 51-fold higher than that experienced by control women. These high-risk women were sisters of patients whose mothers had breast cancer. The disease in these families developed premenopausally, often bilaterally, and was seemingly associated with ovarian function. Since disease susceptibility was transmitted from an affected mother to approximately 30% of her daughters, this early, bilateral form of breast cancer appeared to be strongly heritable. Another, less heritable form was identified in families comprised of at least two affected sisters and unaffected mothers. The risk in these families was 3-fold higher than that of controls, and the disease was primarily postmenopausal, unilateral, and was not strongly associated with ovarian function. No difference was observed in the transmission of breast cancer through paternal and maternal lines of descent.
A genetic study of breast cancer is in progress on 500 patients with positive family histories of the disease. These patients were generally younger and had a higher frequency of bilaterality than did patients with negative family histories. Among familial patients, those with early diagnoses (20 to 44 years) manifested a significantly higher bilaterality rate than did those with intermediate (45 to 54 years) or late diagnoses (55 to 84 years). Blood type O, benign breast disease, and ovarian cysts and tumors also tended to be more common in patients with early diagnoses, while blood type A, diabetes, obesity, hypertension, and uterine disorders were more common in those with later diagnoses. The risk of breast cancer in relatives of patients with bilateral disease was 3 to 4 times higher than that in relatives of patients with unilateral disease. These results could indicate the possibility of at least two types of genetically different breast cancer, and possibly a sporadic type not associated with a family history of the disorder.
Genetic and environmental hypotheses that might explain the patterns of occurrence of breast cancer and associated cancers in 18 large families at high risk of the disease were tested with the use of segregation analysis. For 16 pedigrees, results were consistent with the hypothesis that breast cancer has a genetic etiology. In 2 other families, breast cancer appeared more likely to have an environmental origin. Breast cancer susceptibility is best explained by hypotheses that postulate autosomal dominant susceptibility alleles in 10 families with primarily premenopausal breast cancer and ovarian cancer, in 4 families with primarily postmenopausal breast cancer, and in 2 families with breast cancer, brain tumor, sarcoma, leukemia, and adrenocortical carcinoma in children and young adults. In an accompanying paper, genetic susceptibility in the first 2 groups of families is further explored with the use of linkage analysis.
Maternal age at time of birth was investigated as a risk factor for breast cancer in a study of 1,176 matched case-control pairs. There was no pattern of increasing adjusted relative risk of breast cancer with increasing maternal age, nor was the mean maternal age of cases older than that of controls. Similar negative results were found among the subset of subjects up to 35 years old, a group previously found to show marked maternal age effects. Thus previous reports of an association between breast cancer and advanced maternal age may have been due to chance, extraneous factors, or a misleading reliance on unadjusted mean maternal ages, rather than on relative risks.
Data from a large international case-control study of breast cancer suggested that women born to young mothers had a 25% lower risk of breast cancer. The association was not secondary to a tendency for these women themselves to have had children at early ages. The data provided no indication of a meaningful association between breast cancer risk and birth rank. Confounding was controlled by stratification according to a summary confounder score.
Epidemiologically linked cancers, risk factors for colorectal cancer?
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Concerning a familial association between breast cancer and both prostatic and uterine malianancies Evaluating genetic association among ovarian, breast, and endometrial cancer. Evi-dence for a breast/ovarian cancer relationshiu
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Genetic Epidemiology of Cancer Six families prone to ovarian cancers
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Letter to the editor—One of the authors replies
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Six families prone to ovarian cancers
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Epidemiologically linked cancers, risk factors for colorectal cancer?
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