Thomas R. Fears's research while affiliated with National Institutes of Health and other places

Sunbed/sunlamp use was recently classified as carcinogenic. This report considers characteristics of those who use sunbeds/sunlamps and the effect of sunbed/sunlamp use on their risk for melanoma within a large case-control study carried out in 1991-1992. Females were more likely than males to have used sunbeds/sunlamps. Use by females increased strongly and significantly with younger ages and with the perceived ability to tan. For females, the individual risk for melanoma increased with typical session time and frequency of sessions. Use before age 20, current use and years of use were not significant. The use patterns of occasional and frequent users were very different. We estimate that typical 5-min sessions would increase the risk for melanoma by 19% for frequent users (10+ sessions) and by 3% for occasional users (1-9 sessions). Body sites that are not generally exposed to sunlight were more common sites of primary melanomas for frequent sunbed/sunlamp users. For males, measures of sunbed/sunlamp use were not significantly associated with melanoma risk.

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Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.

Few studies have evaluated the reliability of lifetime sun exposure estimated from inquiring about the number of hours people spent outdoors in a given period on a typical weekday or weekend day (the time-based approach). Some investigations have suggested that women have a particularly difficult task in estimating time outdoors in adulthood due to their family and occupational roles. We hypothesized that people might gain additional memory cues and estimate lifetime hours spent outdoors more reliably if asked about time spent outdoors according to specific activities (an activity-based approach). Using self-administered, mailed questionnaires, test-retest responses to time-based and to activity-based approaches were evaluated in 124 volunteer radiologic technologist participants from the United States: 64 females and 60 males 48 to 80 years of age. Intraclass correlation coefficients (ICC) were used to evaluate the test-retest reliability of average number of hours spent outdoors in the summer estimated for each approach. We tested the differences between the two ICCs, corresponding to each approach, using a t test with the variance of the difference estimated by the jackknife method. During childhood and adolescence, the two approaches gave similar ICCs for average numbers of hours spent outdoors in the summer. By contrast, compared with the time-based approach, the activity-based approach showed significantly higher ICCs during adult ages (0.69 versus 0.43, P = 0.003) and over the lifetime (0.69 versus 0.52, P = 0.05); the higher ICCs for the activity-based questionnaire were primarily derived from the results for females. Research is needed to further improve the activity-based questionnaire approach for long-term sun exposure assessment.

Cytokines are humoral regulatory molecules that act together in immunologic pathways underlying pathogenesis. Grossly elevated blood levels characterize certain diseases; variations within physiologic ranges could also have significance. We therefore evaluated the performance characteristics of a multiplex cytokine immunoassay. We used a fluorescent bead-based (Luminex) immunoassay kit to simultaneously measure interleukin (IL) 1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, IFNgamma, granulocyte colony-stimulating factor, and tumor necrosis factor-alpha. We tested identical aliquots of serum from 38 asymptomatic individuals on three different days and matched sets of serum, heparinized plasma, and acid citrate dextrose plasma from an additional 38 healthy donors expected to have low cytokine concentrations. We applied multiple imputation to calculate unbiased reproducibility estimates for measurements below the limits of detection. Correlations among the cytokines were assessed by Spearman rank order coefficients and principal components analyses. Of the 13 cytokines, 3 were undetectable (IL1beta, IL2, IL5) in more than half of the serum samples. Coefficients of variation for replicate serum measurements ranged from 18% to 44%, with intraclass correlation coefficients ranging from 55% to 98%. Only IL4, IL6, and IL8 had statistically significant correlations (Spearman rho, 0.42-0.94) between serum and acid citrate dextrose or heparin plasma levels. Interindividual differences outweigh substantial laboratory variation for these assays, yielding high intraclass correlation coefficients despite unimpressive coefficients of variation. Plasma measurements generally are not reflective of serum levels and hence are not interchangeable. With their small volume, low cost per test, and multiplex capacity, Luminex-based cytokine assays have potential utility for epidemiologic studies.

Patients with multiple myeloma (MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT (crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively (crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P < .01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 (95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS (RR = 8.4; 95% CI, 5.7-12.2) and MM (RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM.

Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation, differentiation and apoptosis. Although suspected to be involved in prostate carcinogenesis, an association between circulating androgens and prostate cancer has not been clearly established in epidemiologic studies. We conducted a nested case-control study with prospectively collected samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations of prostate cancer with androstenedione (Delta4-A), testosterone (T), sex hormone-binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha-diolG). A total of 727 incident Caucasian prostate cancer cases (age >/= 65 years, N = 396) and 889 matched controls were selected for this analysis. Overall, prostate cancer risks were unrelated to serum T, estimated free and bioavailable T, and SHBG; however, risks increased with increasing T:SHBG ratio (p(trend) = 0.01), mostly related to risk in older men (>/=65 years, p(trend) = 0.001), particularly for aggressive disease [highest versus lowest quartile: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.50-5.09]. No clear patterns were noted for Delta4-A and 3alpha-diolG. In summary, our large prospective study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer. T:SHBG ratio was related to risk in this older population of men, but the significance of this ratio in steroidal biology is unclear. (c) 2008 Wiley-Liss, Inc.