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Association of Quantitative and Qualitative Dermatoglyphic Variable and DNA Polymorphism in Female Breast Cancer Population

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Lavanya Prathap at Saveetha institute of Medical and Technical Sciences
Lavanya Prathap
  • Saveetha institute of Medical and Technical Sciences
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Abstract and Figures

Objective: To investigate the association between dermatoglyphics and the DNA repair genetic variants in female breast carcinoma. Methodology: The distinct dermatoglyphic variables include ≥ six whorls, Finger ridge counts, A-B Ridge Count, ATD angle and Pattern intensity Index are analyzed for its association with the DNA repair variants namely XRCC1 Arg194Trp, XRCC3Thr241Met, ERCC4Arg 415Gln, and ERCC5 Asp1104His. The statistical procedure used to analyze the frequency of association is odds ratio and relative risk ratio. Result: The results suggests that the relative risk is about 2 to 4 times with statistical significance for breast cancer and high risk group for the genes XRCC1 Arg194Trp, ERCC4 Arg 415 Gln, ERCC5 Asp1104His in their dominant model in both breast cancer and high risk group for six or more whorls, Pattern Intensity Index, A-B RC. Conclusion: It can be suggested that dermal ridges can be used as an effective biomarker of genomic instability in breast cancer.
Dermatoglyphic Pattern Frequency Association with Variant Allele of DNA Repair Gene-heterozygous mutant. (*Statistically significant) On analyzing the risk ratio of breast cancer and high risk group for the dominant pattern of inheritance, it presented the relative risk for six or more whorls around three times for both high risk and breast cancer group respectively for genotypes XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 His with statistically significant difference. The relative risk of MFRC is around 2, even though the risk is presented to be 2 it is not statistically significant. The RR for PII-D is >1 for XRCC1 Arg 194 Trp and ERCC5 Asp 1104 His in breast cancer group and RR is 2 for XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 in high risk group with statistical significance. The RR for A-B RC is 2 for XRCC1 Arg 194 Trp and 3 for ERCC4 Arg 415 Gln in breast cancer group and 2 for ERCC5 Asp 1104 His in high risk group with statistical significance (Table-2).
Dermatoglyphic Pattern Frequency Association with Variant Allele of DNA Repair Gene-heterozygous mutant. (*Statistically significant) On analyzing the risk ratio of breast cancer and high risk group for the dominant pattern of inheritance, it presented the relative risk for six or more whorls around three times for both high risk and breast cancer group respectively for genotypes XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 His with statistically significant difference. The relative risk of MFRC is around 2, even though the risk is presented to be 2 it is not statistically significant. The RR for PII-D is >1 for XRCC1 Arg 194 Trp and ERCC5 Asp 1104 His in breast cancer group and RR is 2 for XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 in high risk group with statistical significance. The RR for A-B RC is 2 for XRCC1 Arg 194 Trp and 3 for ERCC4 Arg 415 Gln in breast cancer group and 2 for ERCC5 Asp 1104 His in high risk group with statistical significance (Table-2).
… 
Dermatoglyphic Pattern Frequency Association with Variant Allele of DNA Repair Gene-heterozygous mutant. (*Statistically significant) On analyzing the risk ratio of breast cancer and high risk group for the dominant pattern of inheritance, it presented the relative risk for six or more whorls around three times for both high risk and breast cancer group respectively for genotypes XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 His with statistically significant difference. The relative risk of MFRC is around 2, even though the risk is presented to be 2 it is not statistically significant. The RR for PII-D is >1 for XRCC1 Arg 194 Trp and ERCC5 Asp 1104 His in breast cancer group and RR is 2 for XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 in high risk group with statistical significance. The RR for A-B RC is 2 for XRCC1 Arg 194 Trp and 3 for ERCC4 Arg 415 Gln in breast cancer group and 2 for ERCC5 Asp 1104 His in high risk group with statistical significance (Table-2).
Dermatoglyphic Pattern Frequency Association with Variant Allele of DNA Repair Gene-heterozygous mutant. (*Statistically significant) On analyzing the risk ratio of breast cancer and high risk group for the dominant pattern of inheritance, it presented the relative risk for six or more whorls around three times for both high risk and breast cancer group respectively for genotypes XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 His with statistically significant difference. The relative risk of MFRC is around 2, even though the risk is presented to be 2 it is not statistically significant. The RR for PII-D is >1 for XRCC1 Arg 194 Trp and ERCC5 Asp 1104 His in breast cancer group and RR is 2 for XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 in high risk group with statistical significance. The RR for A-B RC is 2 for XRCC1 Arg 194 Trp and 3 for ERCC4 Arg 415 Gln in breast cancer group and 2 for ERCC5 Asp 1104 His in high risk group with statistical significance (Table-2).
… 
: Association between Dermatoglyphics and Polymorphism of DNA Repair Gene.
: Association between Dermatoglyphics and Polymorphism of DNA Repair Gene.
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Finger Ridge Count
Finger Ridge Count
… 
ATD Angle
+2
ATD Angle
… 
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Original Article:
Association of Quantitative and Qualitative Dermatoglyphic Variable and DNA
Polymorphism in Female Breast Cancer Population
Authors
Lavanya Prathap, Adjunct Assistant Professor, Department of Biomedical Sciences, Gulf Medical University, Ajman, UAE,
Vijayakumar Jagadeesan, Professor, Saveetha Medical College, Saveetha University, Chennai, India,
Prathap Suganthirababu, Assistant Professor, College of Allied Health Sciences. Gulf Medical University, Ajman, UAE,
Deepthi Ganesan, Assistant Professor, Saveetha College of Physiotherapy, Saveetha University, Chennai, India.
Corresponding Address
Dr.Lavanya Prathap,
5/5 Manali New Town,
Chennai-600103.
Email: lavanya.anatomist@gmail.com
Citation
Prathap L, Jagadeesan V, Suganthirababu, P, Ganesh D. Association of Quantitative and Qualitative Dermatoglyphic Variable and
DNA Polymorphism in Female Breast Cancer Population. Online J Health Allied Scs. 2017;16(2):2. Available at
URL:http://www.ojhas.org/issue62/2017-2-2.html
Submitted: Feb 10, 2017; Revised: Apr 4, 2017; Accepted: July 13, 2017; Published: July 30, 2017
Abstract: Objective: To investigate the association between
dermatoglyphics and the DNA repair genetic variants in
female breast carcinoma. Methodology: The distinct
dermatoglyphic variables include ≥ six whorls, Finger ridge
counts, A-B Ridge Count, ATD angle and Pattern intensity
Index are analyzed for its association with the DNA repair
variants namely XRCC1 Arg194Trp, XRCC3Thr241Met,
ERCC4Arg 415Gln, and ERCC5 Asp1104His. The statistical
procedure used to analyze the frequency of association is odds
ratio and relative risk ratio. Result: The results suggests that
the relative risk is about 2 to 4 times with statistical
significance for breast cancer and high risk group for the genes
XRCC1 Arg194Trp, ERCC4 Arg 415 Gln, ERCC5
Asp1104His in their dominant model in both breast cancer and
high risk group for six or more whorls, Pattern Intensity Index,
A-B RC. Conclusion: It can be suggested that dermal ridges
can be used as an effective biomarker of genomic instability in
breast cancer.
Key Words: Dermatoglyphics, DNA repair gene, single
nucleotide polymorphism, breast cancer, genetic instability
Introduction:
Breast Cancer is a complex multi-factorial disease. The
distribution of the status varies between populations based on
their life style, environment, socio-economic status, awareness
and quality of medical care. The Breast cancer incidence peaks
in Asia among women in their 4th decade of life. In United
States and Europe, it peaks among women in their 6th decade.
Cancer statistics in Indian women is 25-30 and the age
adjusted rate is 30-35 new cases per 100,000 women per
year.(1-3) The causative factor of breast cancer cannot be
definitely defined still. It involves the combination of both
genetic and environmental factor. More number of genes are
reported to be responsible for breast cancer. It becomes a very
complex, costly and time consuming process to perform
genetic testing and it involves follow up too. On the other hand
research on dermal ridge patterns are becoming evident as it
has got specific association with breast cancer. Dermal ridge
patterns are said to act as a biomarker of our gene. It reflects
the DNA pattern and the genetic instability. The different
variables of dermal ridges in different areas of palm reflect the
condition of specific gene.(4-7)
Methodology:
The study is being conducted among 150 females in three
groups, each comprising of 50, carried out in the Department
of Anatomy, ACS Medical College and Hospitals, Dr.MGR
Educational and Research Institute, University, Department of
Industrial Biotechnology, Dr. MGR Engineering and Research
Institute, Dr.MGR Educational and Research Institute
University, Tamilnadu, India, and Saveetha Medical College
and Hospital, Saveetha University, Chennai, Tamilnadu,
India. The participants are age matched between 35-60 years.
The study commenced after getting approval from the
Institutional Human Ethical Committee, Saveetha University -
IHEC No-06/10/2012, Dated -09th October 2012. Chennai,
Tamilnadu. The participants are given detailed explanation
about the procedure and their co-operation and willingness is
obtained with an informed consent.
The participants are grouped based on selection criteria. Group
I includes females diagnosed histopathologically for breast
cancer as their primary site of carcinoma. Group II includes
females who are a categorized as high risk for breast cancer
based on their family history for breast cancer (mother, sister
or daughter) or any two criteria based on their endogenous
exposure to estrogen which includes Menstrual history (early
menarche below 12 years, late menopause above 50 years)
Parity status (First Full Term Pregnancy – FFTP above 30
years of age, Nulliparity), Personal history of fibro-adenoma,
obesity, Hormone Replacement Therapy (HRT). Group III
includes normal healthy females. The exclusion criteria for
group I &II includes breast cancer developed as secondaries
from primary site of origin elsewhere, population exposed to
chemotherapy or radiation therapy, population affected with
any other major health problem, Male participants and those
who do not possess proper visible dermal ridges due to their
occupation. The exclusion criteria for group III includes
personal or family history of breast cancer, Personal or family
This work is licensed under a
Creative Commons Attribution-
No Derivative Works 2.5 India License
Online Journal of Health and Allied Sciences
Peer Reviewed, Open Access, Free Online Journal
Published Quarterly : Mangalore, South India : ISSN 0972-5997
Volume 16, Issue 2; Apr-Jun 2017
2
history of non-malignant tumor, population exposed to
chemotherapy or radiation therapy, population affected with
any other major health problem, Male participants, and those
who do not possess proper visible dermal ridges due to their
occupation.
The data for dermatoglyphic analysis are collected using
digital photography and the different variables are analyzed
using computer. After the detailed analysis of various dermal
ridge patterns, the distinctive dermatoglyphic variables are
used as an outcome measure to assess its association with
single nucleotide polymorphism (SNP) status of four DNA
repair genes. The DNA repair variants namely XRCC1
Arg194Trp, XRCC3Thr241Met, ERCC4Arg 415Gln, ERCC5
Asp1104His are analyzed for the study population. The data
collection procedure includes collection of 3ml of peripheral
blood in EDTA coated test tubes through venipucture. The
procedure includes extraction of DNA, followed by
amplification of specific gene segments using Polymerase
Chain Reaction and identification of polymorphism using
Restriction Fragment Length Polymorphism. The frequency of
appearance of all genotypes namely homozygous wild,
heterozygous mutant and homozygous mutant genotypes are
assessed and the frequency of breast cancer and high risk
population are compared with control group. The distinct
dermal ridge variables include ≥ six whorls, Mean Finger
Ridge Count (MFRC), Total Finger Ridge Count (TFRC), A-
B Ridge Count, ATD angle, Pattern Intensity Index-Digital
(PII-D). All the dermal ridge parameter is assessed
individually for its association with all the four SNPs. The
frequencies of appearance of all the genotype for each
distinctive dermal ridge variables are analyzed.
Data Analysis:
The statistical procedure used to analyze the frequency of
association between Dermatoglyphic Pattern and Variant
Allele of DNA Repair Gene is odds ratio, relative risk and the
level of significance using P- value.
Results:
The distinct dermatoglyphic parameters are six and more than
Six Whorls, Mean Finger Ridge Count (MFRC <12.6), Total
Finger Ridge Count (TFRC<126), A-B Ridge count (<34.8),
ATD Angle (<43°), Digital Pattern Intensity Index (PII-
D>12.5). Dermatoglyphic variables Six and more than six
Whorls, Mean Finger Ridge Count (MFRC<12.6), A-B Ridge
count (<34.8) and Digital Pattern Intensity Index (PII-D
>12.5) are associated with significant difference p<0.05 with
XRCC1 Arg194Trp, ERCC4 Arg 415 Gln, ERCC5
Asp1104His in their homozygous wild and heterozygous
mutant type. ERCC5 Asp1104His is associated with
significant difference in their homozygous mutant type. Total
Finger Ridge Count (TFRC<126) is associated with
significant difference with all the four DNA repair genes in
their homozygous wild and heterozygous mutant type. ATD
Angle (<43°) is associated significantly with XRCC3 Thr241
Met in their homozygous wild, heterozygous mutant type and
also homozygous mutant type (p<0.05) (Table 1 & Fig 1).
Figure 1: Dermatoglyphic Pattern Frequency Association
with Variant Allele of DNA Repair Gene – heterozygous
mutant. (*Statistically significant)
On analyzing the risk ratio of breast cancer and high risk group
for the dominant pattern of inheritance, it presented the
relative risk for six or more whorls around three times for
both high risk and breast cancer group respectively for
genotypes XRCC1 Arg 194 Trp, ERCC4 Arg 415 Gln, ERCC5
Asp 1104 His with statistically significant difference. The
relative risk of MFRC is around 2, even though the risk is
presented to be 2 it is not statistically significant. The RR for
PII-D is >1 for XRCC1 Arg 194 Trp and ERCC5 Asp 1104
His in breast cancer group and RR is 2 for XRCC1 Arg 194
Trp, ERCC4 Arg 415 Gln, ERCC5 Asp 1104 in high risk
group with statistical significance. The RR for A-B RC is 2 for
XRCC1 Arg 194 Trp and 3 for ERCC4 Arg 415 Gln in breast
cancer group and 2 for ERCC5 Asp 1104 His in high risk
group with statistical significance (Table-2).
Figures 2,3,4: Dermatoglyphic Patterns - Whorl, Arch and Ulnar Loop
2
Table 1: Association between Dermatoglyphics and Polymorphism of DNA Repair Gene.
Gene &Codon
Genotype
Negative and Positive pattern Frequency
≥6 Whorls
N=63(42)
MFRC <12.6,
N= 105(70%)
TFRC,
<126, N=100(66)
A-B ridge count
<34.8- n=67(45)
PII- D->12.5
N=78(52)
XRCC1
R194W
R/R
OR (CI at 95%)
60.43
(7.90-462.0)
4.14
(1.18 – 14.5)
3.43
(1.11-0.55)
7.62
(2.70-21.5)
35.50
(4.6-270.0)
P Value
0.0001
0.03
0.03
0.0001
0.0006
R/W
OR (CI at 95%)
0.017
(0.002-0.13)
0.25
(0.07-0.89)
0.30
(0.10-0.95)
0.14
(0.04-0.39)
0.02
(0.003-0.2)
P Value
0.0001
0.03
0.04
0.0002
0.0007
W/W
OR (CI at 95%)
0.2
(0.009-5.94)
0.76
(0.03-19.15)
0.65
(0.02-16.4)
0.26
(0.01-6.62)
0.35
(0.01-8.88)
P Value
0.3819
0.87
0.78
0.41
0.35
XRCC3
T241W
T/T
OR (CI at 95%)
1.77
(0.7-4.06)
0.72
(0.30-1.72)
0.28
(0.12-0.67)
1.09
(0.47-2.48)
0.90
(0.39-2.06)
P Value
0.17
0.46
0.004
0.83
0.81
T/M
OR (CI at 95%)
0.55
(0.23-1.34)
1.50
(0.60-3.73)
2.84
(1.16-6.92)
0.94
(0.39-2.27)
1.10
(0.45-2.63)
P Value
0.191
0.38
0.02
0.90
0.81
M/M
OR (CI at 95%)
0.7176
(0.09-5.23)
0.77
(0.07-7.63)
6.31
(0.64-62.3)
0.80
(0.11-5.8)
1.08
(0.14-7.91)
P Value
0.74
0.82
0.11
0.82
0.83
ERCC4
R415Q
R/R
OR (CI at 95%)
8.571
(3.4-21.5)
5.86
(1.69-20.35)
24.1
(3.1-182.5)
16.01
(5.25-48.7)
6.16
(2.3-16.01)
P Value
<0.0001
0.005
0.002
<0.0001
0.94
R/Q
OR (CI at 95%)
0.1522
(0.06-0.38)
0.20
(0.05-0.72)
0.05
(0.006-0.3)
0.07
(0.02-0.24)
0.20
(0.07-0.53)
P Value
<0.0001
0.01
0.003
<0.0001
0.0002
Q/Q
OR (CI at 95%)
0.075
(0.004-1.46)
0.24
(0.01-4.70)
0.21
(0.01-4.02)
0.08
(0.004-1.5)
0.11
(0.006-2.1)
P Value
0.08
0.35
0.30
0.09
0.14
ERCC5
D1104H
D/D
OR (CI at 95%)
22.868
(9.254-56.5)
8.63
(2.88-25.83)
24.00
(5.5-104.1)
72.59
(20.3-259)
15.81
(6.11-40.8)
P Value
0.0001
0.0001
<0.0001
<0.0001
<0.0001
D/H
OR (CI at 95%)
0.0623
(0.02-0.15)
0.14
(0.04-0.42)
0.05
(0.01-0.22)
0.01
(.005-0.06)
0.08
(0.03-0.21)
P Value
<0.0001
0.0005
0.0001
<0.0001
<0.0001
H/H
OR (CI at 95%)
0.06
(0.003-1.12)
0.20
(0.01-3.70)
0.17
(0.009-3.1)
0.06
(0.003-1.2)
0.09
(0.005-1.6)
P Value
0.05
0.20
0.23
0.07
0.10
Table 2: Risk Ratio and Odds Ratio of Polymorphism (Dominant Model) In Breast Cancer and High Risk Population with Distinct Dermatoglyphic
Pattern.
Dermatoglyphic Variables
Groups
RR/OR/ P -value
XRCC1
Arg194Trp
XRCC3
Thr214Met
ERCC4
Arg415Gln
ERCC5
Asp1104His
≥ six whorls
Breast cancer
RR (95% CI)
3(1.89-4.76)
1(0.45-2.02)
3(1.51-4.05)
3(1.60-4.21)
OR(95% CI)
∞
1(0.20-4.12)
13(2.48-66.16)
13(3.68-45.8)
P Value
<0.0001
1
0.0007
<0.0001
High Risk
RR(95% CI)
3(1.87-4.34)
1(0.72-2.45)
3(1.46-4.31)
3(1.74-6.11)
OR(95% CI)
∞
2(0.44-7.5)
9.06(2.13-38.49)
15(3.51-66.84)
P value
<0.0001
0.48
0.002
<0.0001
MFRC <12.6
Breast cancer
RR(95% CI)
2(1.01-1.32)
1(0.53-1.21)
1(1.01-1.34)
1.17(0.96-1.51)
OR(95% CI)
∞
0.23(0.03-1.67)
∞
7(0.74-70.51)
P Value
0.30
0.17
0.16
0.14
High risk
RR(95% CI)
1(0.84-1.40)
1(0.67-1.31)
1(0.72-1.25)
1.22(0.98-1.52)
OR(95% CI)
1(0.20-17.5)
1(0.11-4.16)
1(0.15-3.60)
5(0.59-46.5)
P Value
0.67
1
1
0.13
PII>12.5
Breast cancer
RR(95% CI)
1.3(1.13-1.69)
1(0.43-1.30)
1(0.76-1.36)
1.5(1.07-2.25)
OR(95% CI)
∞
0.33(0.06-1.72)
1(0.24-5.06)
9(1.72-50.61)
P Value
0.04
0.33
1
0.008
High risk
RR(95% CI)
2(1.19-2.45)
1(0.56-1.76)
2(1.24-2.77)
2(1.05-2.57)
OR(95% CI)
8(0.94-70.4)
1(0.24-4.11)
8(1.54-40.09)
4(1.08-14.80)
P Value
0.03
1
0.01
0.04
A-B RC <34.8
Breast cancer
RR(95% CI)
2(1.32-3.19)
1(0.31-2.08)
3(1.65-4.26)
∞
OR(95% CI)
8(1.63-43.17)
0.7(0.15-3.23)
27(3.22-234)
∞
P Value
0.0009
0.71
0.0001
3.75
High risk
RR(95% CI)
1(0.91-1.80)
1(0.46-1.36)
1.3(0.99-1.84)
2(1.32-2.59)
OR(95% CI)
3(0.51-14)
0.5(0.11-2.13)
4(0.74-19.6)
∞
P Value
0.30
0.43
0.17
0.0006
RR – Risk ratio, OR- Odds ratio
1
Figure 5: Finger Ridge Count
Figure 6: ATD Angle
Figure 7: A-B Ridge Count
Discussion:
Of all the genes involved in the process of carcinogenesis,
DNA Repair genes forms the corner stone. Instability of DNA
Repair gene leads to instability of proto-oncogene, oncogene,
tumor suppressor gene and suicidal genes. It has got specific
pathways namely NER,BER,HR,DSB which takes
important role in repairing the damages caused by aging,
exposure to oxidative stress etc., The DNA Repair Gene is the
back bone of all the other genes. The four SNP are found to be
reported in number of studies to be associated with breast
cancer (8-11), which is in agreement with the present study. In
observation, three SNPs namely XRCC1 Arg194Trp, ERCC4
Arg 415 Gln, ERCC5 Asp1104His reported to have significant
associated with breast cancer and high risk in the present
study. The Results of XRCC3 Thr241Met is inconclusive.
On Observation dermatoglyphic variables six and more than
six whorls, mean finger ridge count (MFRC<12.6), A-B ridge
count (<34.8) and digital pattern intensity index (PII-D >12.5)
are observed to be associated in increased frequency with the
variant allele of DNA repair gene single nucleotide
polymorphism rs1799782, rs1800067 and rs17655 in their
heterozygous mutant type and with rs17655 in their
homozygous mutant type also. Total finger ridge count
(TFRC<126) is observed to be associated in increased
frequency with the variant allele of DNA repair gene Single
nucleotide polymorphism rs1799782, rs861539, rs1800067
and rs17655 in their heterozygous mutant type alone. ATD
Angle (<43°) observed to be associated in increased frequency
with the variant allele of DNA repair gene single nucleotide
polymorphism rs861539 in their heterozygous mutant type
and homozygous mutant type and rs17655 in their hetero
mutant type. The relative risk is about 2 to 4 times with
statistical significance for breast cancer and high risk group for
the genes XRCC1 Arg194Trp, ERCC4 Arg 415 Gln, ERCC5
Asp1104His in their dominant model in both breast cancer and
high risk group for the variables six or more whorls, PII-D, A-
B RC.
The study of dermal ridge patterns on the skin of palm of hand
and sole of foot play a vital role in the field of forensic,
anthropology, criminology and medicine.(12) Because of less
2
number of researches in dermatoglyphics, its role in medical
field is very limited. Importance of dermal ridges is still given
only in the field of forensic, person identity etc,. The hidden
secrets of dermal ridges of skin need to be broken in the field
of medicine to be used as a useful, powerful, sensitive, and
cost-effective, less time consuming screening, diagnostic
procedure. Number of studies reported the association of
dermal ridge pattern and breast cancer.(13-18) But still the
concept of development of dermal ridges and its genetic base
remains unclear. Similarly number of studies reported the
genetic basis of breast cancer.(8,10,11) As specific
dermatoglyphic parameters are related to breast cancer and
both breast cancer and the dermal ridges have the genetic base,
it is suggested that there can be a common genetic basis for
distinct dermal ridge in relation to breast cancer. Breast cancer
is expressed only after getting exposed to inducing factors, but
dermal ridges are developed in the womb itself and the status
of gene is expressed in the dermal ridges which remains
unchanged forever. So even before the process of
carcinogenesis begins or the appearance of visible tumor one
can be screened for breast cancer risk which aids for effective
preventive measures and early therapies and improves the
quality of life. To investigate this hypothesis the association of
distinct dermal ridges and DNA repair gene SNPs are observed
for the first time.
Conclusion
The results of the present study confirmed the involvement of
XRCC1 Arg194Trp, ERCC4 Arg 415 Gln, and ERCC5
Asp1104His in breast cancer particularly in population with
distinct dermal ridge pattern. It can be suggested the dermal
ridges can be used as an effective biomarker of genomic
instability in breast cancer. Thus the study aimed to investigate
the genetic background of association between breast cancer
and distinct palm ridge pattern. It can be suggested that the
dermal ridge pattern can be used as a biomarker of specific
DNA Repair gene polymorphism that serves as a screening
procedure.
Acknowledgments: We would like to deliver sincere thanks
to Dr. MGR Educational & Research Institute University and
Saveetha University, Tamilnadu, India.
Conflict of interest: Nil
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... Breast cancer is the most common type of cancer among women worldwide [1] and the main cause of their death [2] . In most cases, breast cancer is diagnosed too late [3] . Early diagnosis of breast cancer could prevent stage progress and the death of the patients [4] . ...
... It has barriers such as costs, fear, embarrassment, selfdenial, lack of family support, issues in centers providing screening, culture, and religion [8][9][10][11][12][13] . The causes of breast cancer are a combination of genetic and environmental factors [3] . Thus, predicting breast cancer even before mass formation could be a solution by using data analysis from cancer-causing agents in other patients and creating models. ...
Early Breast Cancer Prediction Using Dermatoglyphics: Data Mining Pilot Study in a General Hospital in Iran
Article
Full-text available
  • Oct 2021
Aims: Dermatoglyphic is the study of skin patterns on hands and feet. It has been shown in some studies that specific finger patterns could be a risk factor for breast cancer. Thus, this study aims to evaluate fingerprint patterns and other easy-to-obtain features in the risk of breast cancer. Instrument & Methods: This descriptive study was conducted in 2020. A dataset containing 462 records included female patients in Imam Khomeini Hospital Complex, Tehran, Iran. The factors' weight was determined by the Information Gain index. Predictive models were built once without fingerprint features and once with fingerprint features using Naïve Bayes, Decision Tree, Random Forest, Support Vector Machine, and Deep Learning classifiers. RapidMiner 9.7.1 Software was used. Findings: The most important factor determining breast cancer were age, having a child, menopause situation, and menopause age. The best performance was the Random Forest model with accuracy and Area under Curve of a Receiver operating characteristic of 84.43% and 0.923, respectively. The fingerprint patterns feature increased the RF accuracy from 79.44% to 84.43%. Conclusion: An early breast cancer screening model could be built with the use of data mining methods. The fingerprint patterns could increase the performance of these models. The Random Forest model could be used. The results of such models could be used in designing apps for self-screening breast cancer.
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... A method called myofascial release, which is used in manual therapy, has been found to improve head and neck posture and has an effect on how postural alignments are maintained. Prathap L et al.,suggested that the dermal ridges serve as a useful diagnostic of genetic instability in breast cancer 18 . Our research participants also reported short-arm force, which makes using one's hands challenging. ...
Effectiveness of Myofascial Release on Mouth Opening in Subjects with Post Operative Buccal Mucosa Carcinoma
Article
Full-text available
  • Jan 2024
Background: Patient treatment after surgical excision of buccal mucosal carcinoma should prioritise symptomrelief and cancer prevention. Mouth exercise physiotherapy is widely regarded as a staple for expanding themouth, either on its own or in conjunction with other modalities. In order to better understand the manufactureand clinical effectiveness of Triscare mouth exercising devices in subjects with CA buccal mucosa, the currentstudy was conducted.Purpose: This study aims to evaluate the effectiveness of Myofascial release for postoperative buccal cancerpatients.Materials and Methods: Subjects with buccal mucosa carcinoma were recruited from Saveetha Dental Collegeand Hospital for an experimental research using inclusion and exclusion criteria. Two week postoperative BuccalMucosa Carcinoma subject volunteer. The participants were secretly separated into two groups using envelopes.Before and after treatment, jaw exercise and Myofascial release groups had their mouth opening and quality of lifeevaluated. Statistical analysis was performed on the collected data, and conclusions were drawn.Results: At the 4-week follow-up, the intervention group’s mean MO (48.06mm) was significantly higher than thecontrol group’s (44.66 mm) (p 0.002), and the intervention group also reported significantly higher GTQ scores andhigher health-related quality of life scores across all domains and items.Conclusion: We concluded that Participants in the intervention group improved more than those in the controlgroup, and they also reported higher levels of engagement with and satisfaction with their therapy.
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... Breast cancer can be treated stage wise. The experience from our previous studies [4][5][6][7][8][9][10][11][12][13] have led us to focus on the current topic. ...
Activity of Hydroethanolic Leaf Extract of Tecoma stans against Breast Cancer Cells Line - MCF - 7
Article
  • Dec 2021
Background: Cancer is abnormal growth of cells, which invade or spread to other parts of the body. There are over 200 types of cancers. Breast cancer is a cancer which develops in tissues of the breast, most commonly originating from the inner lining of milk ducts or lobules that supply ducts with milk. Tecoma stans commonly known as trumpet flower is a yellow trumpet shaped flower belonging to Bignoniaceae, and is native to Americas. It has anti cancer and anti proliferative properties. Aim: Aim of the is to analyse the anti cancer activity of Tecoma stans against breast cancer cells MCF-7. Materials and Methods: Breast cancer cell line (MCF-7) was purchased from National Centre for Cell Sciences (NCCS), Pune, India. Cell viability test was done by MTT assay. BcL2 and BclxL gene expression analysis was done by Real Time-PCR. The obtained data were analysed statistically by one-way analysis of variance and Duncan’s multiple range test with Graph Pad Prism version 5 to analyse the significance. The significance was considered at p<0.05 level in Duncan’s test. Results: The results suggest Bcl2 mRNA gene expression is reduced on induction of 400, 500 ug/ml of Tecoma stans with significant difference in comparison with control. Bcl-xL mRNA gene expression is slightly reduced on induction of 400, 500 μg/mL of Tecoma stans with no significant difference in comparison with control. Conclusion: From the obtained results, it can be concluded that hydroethanolic leaf extract of Tecoma stans possess anticancer activity against breast cancer cells with respect to Bcl2 mRNA gene expression as compared to Bcl xL mRNA gene expression. If complete research is done, we can use this drug to treat various cancers.
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... As a result, we attempted to discover the most common position and size of the mental foramen in adult South Indians in our current study [3]. The experience from our previous studies [4][5][6][7][8][9][10][11][12][13] have led us to focus on the current topic. ...
Variation in Mental Foramen of Mandible among South Indian Population- A Radiographic Analysis
Article
  • Dec 2021
Background: The mental foramen (MF) is a hole in the body of the mandible that is placed on the antero-lateral side. Between the upper and lower mandibular borders, it can be found. It sends signals to the brain's nerves and blood vessels. Many researches have documented variations in the placement of the MF among different ethnic groups, as well as variations in its forms. It's commonly found beneath the first premolar teeth. The study's goal is to look at where mental foramen are found in the South Indian population. Materials and Methods: A total of 100 distinct OPGs from the South Indian population were used in the investigation. The position of mental foramen for various mandibles was visually examined using OPGs, and the data was tallied and analyzed using SPSS. Results: From the results it is suggested that the maximum frequency for the right side is at location 2 which is in the longitudinal axis of 1st premolar. 14.0% at location 1, 31.6% at location 2, 21.1% at location 3. 17.3% at location 4. 10% at location 5, 6% at location 6. The situation of mental foramen at the axis of 1st premolar was observed to have a high frequency of occurrence in the age group of 26-35. Conclusion: The Mental foramen in study population is mostly found in the longitudinal axis of 1st premolar. The clinical students and surgeons should know the existence of mental foramen at surgical procedures using mandibular premolar and molar regions. Future studies with large sample sizes should be conducted to make the results conclusive.
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... Caspase 3 mRNA is an apoptosis gene whose expression causes cancer cells to die. The experiences from our previous studies [8,9,10,9,11,12,13,14,12,14,15,16,17] have led us to focus on the current topic. Our researchers has elaborate stuff and research experience that has translate into good quality research papers [18][19][20][21][22][23][24][25][26][27][28][29][30][31]32,[33][34][35][36][37]. ...
Role of Endogenous Serotonin Replica Mediated Through β-Catenin/Wnt Signaling in Lung Cancer Prevention and Prognosis - an in-vitro Study in A549 Cancer Cell Lines
Article
  • Dec 2021
Background: Lung cancer is still the most common cause of carcinoma-related death in the globe. Non-pharmacological treatments such as physical activity and exercise have been shown to improve quality of life and provide better results in lung cancer patients. Lung cancer patients usually lack adequate amounts of physical activity and exercise, both of which can improve quality of life. Aim: To analyse Chemotherapeutic potential of endogenous serotonin replica mediated through β-catenin/Wnt signaling in lung tumor cell lines (A549). Methods and Materials: The National Centre for Cell Sciences (NCCS), Pune, India, provided the human lung cancer cell line (A549). MTT assay was used to determine cell viability. Real-time PCR was used to examine -Catenin mRNA, Wnt mRNA, and GSK mRNA gene expression. The significance of the acquired data was determined using one-way analysis of variance and Duncan's multiple range test with Graph Pad Prism version 5. Duncan's test was used to determine significance at the 0.05 level. Results: The Results suggest that maximum inhibition of cell growth was at concentration (2-4 mM/ml) used in this study when compared to control. The cancer cells were significantly inhibited and it was found that there was notable reduction in GSK mRNA gene expression, β-Catenin, Wnt when compared to control at a dose of 2 mM/ml. Conclusion: It may be concluded, based on the analyses' findings and the study's limitations, that the role of exercise induced endogenous serotonin may act as the regulator of wnt/β-catenin signaling in lung cancer cells. The exercise may help in maintaining the equilibrium of the gene expression by modeling Wnt/β-catenin signaling pathway and act as a protective factor in prevention.
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... Assessment of gonial angle for sex determination according to age and gender are evidenced in certain studies [2][3][4][5]. The experience from our previous studies conducted among different fields [6,7,8,9,10,11,12,13,14,15] have ed us to focus on the current topic.Measurement of gonial angle is essential for the treatment and surgery in orthodontics. Therefore, accurate determination of the gonial angle is important for assessing the orthodontic cases [16]. ...
Gender Determination using Gonial Angle - A Panoramic Study among South Indian Population
Article
  • Dec 2021
Introduction: Sex determination is a valuable and important factor in the forensic dentistry. Mandible has several useful traits for sex determination. Forensic practitioners study this by two methods: morphological and metrical analyses. Among various methods, the gonial angle may be used to differentiate male and female strongly to express sexual dimorphism. Aim: To analyse the gender determination using gonial angle as panoramic study among south indian population. Materials and Methods: This is a retrospective study conducted among 200 individuals. Gonial angle is a measurement taken by measuring the angle between the 2 tangents from the gonion.As a standard procedure, measurement of right gonial angle and left gonial angle were carried out by Adobe Photoshop and the results were recorded and analysed statistically using SPSS tool. Results: The mean right gonial angle for males is 95.25 and for females is 95.22 The mean left gonial angle for males is 95.39 and for females is 95.15. The significance of the right gonial angle is P=0.874 and significance of the left gonial angle is P= 0.147. The total mean value for right gonial angle was found to be 95.23 and for left gonial angle is 95.27. Therefore, there was no significant difference found between the right and left gonial angle. Conclusion: Within the limitations of the study, there is no statistically significant difference observed between males and females in the gonial angle measurements. The Gonial angle measurements can be used to determine the gender and the growth pattern of the mandible. Measurement of gonial angle has its own surgical importance too in the field of orthodontics and therefore future studies should be carried out using larger samples to get reliable results.
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... Diagnosis of elongated styloid process is confirmed by analysis of radiographs and clinical examination of the patient is considered as an important tool. The experience from our previous studies [12][13][14][15][16][17][18][19][20][21][22] have led us to focus on the current topic [12]. ...
Morphological Characteristic and Incidence of Elongate Styloid Process in South Indian Population: A Case Series
Article
  • Dec 2021
Introduction: Styloid process is a slender osseous projection, cylindrical and sharp projection of the temporal bone, located in front of stylomastoid foramen. Styloid process is from Reichert’s cartilage of the second branchial arch, this is a part of the splanchnocranium. This is Connected to the hyoid bone through the Stylohyoid ligament. The morphology of the Styloid process is due to hormonal and genetic changes. Orthopantomography is a radiographic method used to visualise mandibles. It also provides a rotational view of the jaw. The aim of the study is to analyse the elongation of the Styloid process in the South Indian population. Materials and Methods: The study was conducted in dental institutions with convenience sampling. The random orthopantomogram sample was collected from a dental institution. Total number of orthopantomogram involved in the study was 80 (40-males and 40-females) that is used to examine elongation of the Styloid process in the South Indian population. The minimised sampling bias is done by stratification according to age and gender. Statistical Analysis: The data were analysed by using SPSS software. The probability value p< 0.05 is considered as significant and the value p>0.05 was considered as not significant. Results: This study showed various types of Styloid processes in males and females. However we concluded that there is a difference in shape of Styloid processes. The most common type of the Styloid process found in males is pseudo articulated (32.5%) whereas in females the most common type of Styloid process found is uninterrupted (37.5%) Conclusion: From the current study we have concluded that the pseudo articulated Styloid process is more in males whereas uninterrupted is more in females. Only retrospective studies were done so far. Therefore in future studies with live models and larger sample size should be conducted.
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... At the same time vigorous exercise above threshold limits when tested is found to cause raise in the free radical production. 10,[12][13][14][15] Oakley -Girvan I in 2017, in their population based sample, analyzed the impact of exercise in leucocyte telomere length in premenopausal breast cancer survivors. This is a randomized controlled trial of 273 premenopausal women, 55 years of age. ...
Effect of Physical Exercise in Remodeling Telomere Length and Cancer Prevention in an Epigenetic Prospect – A Systematic Review
Article
Full-text available
  • Jun 2021
Background: Physical exercise has its impact at the molecular level and aids in healthy well-being of an individual. The current systematic review emphasis on the impact of physical exercise on the telomere length in cancer prevention through epigenetic mechanism. Evidences support the impact of physical exercise in alteration of telomere length through its influence in telomerase activity. The aim of the systematic review is to analyze the effect of physical exercise in remodeling the telomere length in cancer prevention in an epigenetic prospect. Material and Methods: We conducted a qualitative systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covers articles ranging from the year 2010 to 2020. The Database used for literature searches are PubMed, Cochrane, Science Direct and Google scholar. The Medical Subject Headings (MeSH) used for search include ‘Cancer’ ‘exercise’ ‘Telomere length’ ‘telomerase expression’. The outcome variables include the telomere length, telomerase activity, telomere protein stabilizing gene expression status, Micro RNA expression status. Results: After exclusion of irrelevant articles 05 records are selected for final inclusion of the study and are analyzed using a Cochrane risk of bias assessment tool and SANRA tool found to be at low risk of bias and moderate quality respectively. The findings suggest chronic exercise is found to modulate the genetic and epigenetic equilibrium by either up regulation of p53 and p16 expression and stabilizing the telomerase activity within the limits or by increasing the telomerase activity and stabilizing the p53 and p16 expression within limits and impact telomere length, thus maintaining the genetic and epigenetic equilibrium. Conclusion: Based on the evidences collected it can be suggested that chronic moderate intensity aerobic exercise in a lifelong practice shows beneficial effects in a dose-response manner in cancer prevention in a novel way by modulating telomeres through epigenetic mechanism.
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EFFICACY OF COMBINING TENS WITH ALTERNATE NOSTRIL BREATHING AMONG GERIATRIC HYPERTENSIVE SUBJECTS
Article
Full-text available
  • May 2021
BACKGROUND: Geriatric population is getting increased worldwide.In addition to the ageing process hypertension will be one of the risk factor for various diseases. At the same time increasing the anti hypertensive drug dosage and adding up new drugs at the late age, could lead to potential side effects.Thus along with the pharmacological therapy an adjunct therapy is neededto keep the blood pressure under controlled levels.This study aims to explore the efficacy of Combining Tens with Alternate Nostril Breathing Among Geriatric Hypertensive Subjects. METHODS: An Experimental study was carried out with 68 participants. Experimental group received Tens therapy along with the alternate nostril breathing exercise. Control group received pharmacological therapy along with alternate nostril breathing therapy. The Mean arterial pressure was recorded pre and post to the intervention by blinded tester who was not aware about group allotment. RESULT: Pre-test and post-test mean and standard deviation values of MABP of Experimental group found to be 119.69 (+4.93) and post-test be 115.73(+4.86) with p value of <0.0001. It is proved that there is statistically significant reduction in MABP in experimental group treated with Tens therapy and alternate nostril breathing exercise. CONCLUSION: Combining Tens therapy and alternate nostril breathing exercise has shown to be effective in keeping the blood pressure levels under control among geriatric population. KEY WORDS: Tens, Alternate nostril breathing, Geriatrics, Hypertension,Mean arterial blood pressure
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Predicting the COVID-19 spread, recoveries and mortalities rates in Saudi Arabia using ann
Article
Full-text available
  • Dec 2020
The worldwide pandemic of the COVID-19 has become the main national security issue for almost all nations. The advancement of accurate prediction models provides insights into the spread of this infectious disease. In fact, the high uncertainty and low size of data have caused some epidemiological models that show low accuracy for long-term prediction. Although the related works include many attempts to deal with this issue, the robustness abilities of current models need to be enhanced. In this paper, to achieve the main contribution, a prediction model using Artificial Neural Networks (ANNs) approach is developed based on the COVID-19 data from March 2, 2020 to August 5, 2020 to predict COVID-19 spread rate, recoveries rate, and mortalities rate in Saudi Arabia using Python programming language for the implementation stage and code has been developed to achieve the final results. The evaluation in this paper has conducted through calculating the values for Correlation Coefficient (CC), Mean Absolute Error (MAE), and Mean Square Error (MSE). However, the results are promising by achieving low MAE with average value 0.05 and MSE with average value 0.02, and high Correlation Coefficient for all targets’ rates with average value 0.97. Paper further recommends that real novelty in spread prediction can be realized through using other machine learning models with different types of COVID-19 data.
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Qualitative and quantitative dermatoglyphic traits in patients with breast cancer: A prospective clinical study
Article
Full-text available
  • Mar 2007
  • BMC CANCER
Breast cancer is one of the most extensively studied cancers and its genetic basis is well established. Dermatoglyphic traits are formed under genetic control early in development but may be affected by environmental factors during first trimester of pregnancy. They however do not change significantly thereafter, thus maintaining stability not greatly affected by age. These patterns may represent the genetic make up of an individual and therefore his/her predisposition to certain diseases. Patterns of dermatoglyphics have been studied in various congenital disorders like Down's syndrome and Kleinfelter syndrome. The prints can thus represent a non-invasive anatomical marker of breast cancer risk and thus facilitate early detection and treatment. The study was conducted on 60 histo-pathologically confirmed breast cancer patients and their digital dermatoglyphic patterns were studied to assess their association with the type and onset of breast cancer. Simultaneously 60 age-matched controls were also selected that had no self or familial history of a diagnosed breast cancer and the observations were recorded. The differences of qualitative (dermatoglyphic patterns) data were tested for their significance using the chi-square test, and for quantitative (ridge counts and pattern intensity index) data using the t- test. It was observed that six or more whorls in the finger print pattern were statistically significant among the cancer patients as compared to controls. It was also seen that whorls in the right ring finger and right little finger were found increased among the cases as compared to controls. The differences between mean pattern intensity index of cases and controls were found to be statistically significant. The dermatoglyphic patterns may be utilized effectively to study the genetic basis of breast cancer and may also serve as a screening tool in the high-risk population. In a developing country like India it might prove to be an anatomical, non-invasive, inexpensive and effective tool for screening and studying the patterns in the high-risk population.
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Palmar dermatoglyphics in carcinoma breast of Indian women
Article
Full-text available
  • Jan 2010
The present study was planned to assess the relationship of palmar dermatoglyphic patterns of hands in women with breast cancer and or at risk for developing breast cancer. This study was conducted on 100 histopathologically confirmed breast cancer patients in women and their digital dermatoglyphic patterns were studied to assess their association with the type and onset of breast cancer. Simultaneously 100 age-matched controls were also selected with no self or familial history of a diagnosed breast cancer and the observations were recorded. The differences of qualitative (dermatoglyphic patterns) data were tested for their significance using the chi-square test, and Student's t-test was used for quantitative (ridge counts and pattern intensity index) data analysis. The results of the study indicated statistically significant changes in finger ridge count and fingertip pattern in cases of carcinoma breast as compared to the control group. Palmar dermatoglyphics is simple, inexpensive, anatomical and non-invasive and may be used as a reliable indicator for screening of high-risk population in developing country like India, for early detection and early therapy, thus reducing the morbidity and mortality in cases of carcinoma breast.
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DNA Repair Gene Variants Associated with Benign Breast Disease in High Cancer Risk Women
Article
Full-text available
  • Feb 2009
Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg(194)Trp (rs1799782) and ERCC4 Arg(415)Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95% confidence interval (95% CI), 1.06-1.74 and HR, 1.39; 95% CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95% CI, 1.52-4.66; P(interaction) = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups.
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Spectrum of Breast Cancer in Asian Women
Article
Full-text available
  • Jun 2007
Breast cancer is the leading cause of cancer-related deaths in Asia, and in recent years is emerging as the commonest female malignancy in the developing Asian countries, overtaking cancer of the uterine cervix. There have been no studies objectively comparing data and facts relating to breast cancer in the developed, newly developed, and developing Asian countries thus far. This multi-national collaborative study retrospectively compared the demographic, clinical, pathological and outcomes data in breast cancer patients managed at participating breast cancer centers in India, Malaysia and Hong Kong. Data, including those on the availability of breast screening, treatment facilities and outcomes from other major cancer centers and cancer registries of these countries and from other Asian countries were also reviewed. Despite an increasing trend, the incidence of breast cancer is lower, yet the cause-specific mortality is significantly higher in developing Asian countries compared with developed countries in Asia and the rest of the world. Patients are about one decade younger in developing countries than their counterparts in developed nations. The proportions of young patients (< 35 years) vary from about 10% in developed to up to 25% in developing Asian countries, which carry a poorer prognosis. In the developing countries, the majority of breast cancer patients continue to be diagnosed at a relatively late stage, and locally advanced cancers constitute over 50% of all patients managed. The stage-wise distribution of the disease is comparatively favorable in developed Asian countries. Pathology of breast cancers in young Asian women and the clinical picture are different from those of average patients managed elsewhere in the world. Owing to lack of awareness, lack of funding, lack of infrastructure, and low priority in public health schemes, breast cancer screening and early detection have not caught up in these under-privileged societies. The inadequacies of health care infrastructures and standards, sociocultural barriers, economic realities, illiteracy, and the differences in the clinical and pathological attributes of this disease in Asian women compared with the rest of the world together result in a different spectrum of the disease. Better socioeconomic conditions, health awareness, and availability of breast cancer screening in developed Asian countries seem to be the major causes of a favorable clinical picture and outcomes in these countries.
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Estrogen-Induced Breast Cancer: Alterations in Breast Morphology and Oxidative Stress as a Function of Estrogen Exposure
Article
  • Oct 2008
  • TOXICOL APPL PHARM
Epidemiological evidence indicates that prolonged lifetime exposure to estrogen is associated with elevated breast cancer risk in women. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. In the present study, we investigated changes in breast morphology and oxidative stress following estrogen exposure. Female ACI rats were treated with 17beta-estradiol (E(2), 3 mg, s.c.) for either 7, 15, 120 or 240 days. Animals were euthanized, tissues were excised, and portions of the tissues were either fixed in 10% buffered formalin or snap-frozen in liquid nitrogen. Paraffin-embedded tissues were examined for histopathologic changes. Proliferative changes appeared in the breast after 7 days of E(2) exposure. Atypical ductal proliferation and significant reduction in stromal fat were observed following 120 days of E(2) exposure. Both in situ and invasive carcinomas were observed in the majority of the mammary glands from rats treated with E(2) for 240 days. Palpable breast tumors were observed in 82% of E(2)-treated rats after 228 days, with the first palpable tumor appearing after 128 days. No morphological changes were observed in the livers, kidneys, lungs or brains of rats treated with E(2) for 240 days compared to controls. Furthermore, 8-isoprostane (8-isoPGF(2alpha)) levels as well as the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase, were quantified in the breast tissues of rats treated with E(2) for 7, 15, 120 and 240 days and compared to activity levels in age-matched controls. 8-isoPGF(2alpha) levels displayed time-dependent increases upon E(2) treatment and were significantly higher than control levels at the 15, 120 and 240 day time-points. 8-isoPGF(2alpha) observed in E(2)-induced mammary tumors were significantly higher than levels found in control mammary tissue from age-matched animals. Similarly, alterations in glutathione peroxidase and superoxide dismutase activities were detected in both mammary and tumor tissue from E(2)-treated rats. Taken together, our data reveal that proliferative changes in the breast tissue of ACI rats are associated with increases in 8-isoPGF(2alpha) formation as well as changes in the activities of antioxidant enzymes. These oxidative changes appear to be a function of E(2) exposure and occur prior to tumor development.
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Synergistic Effects of Polymorphisms in DNA Repair Genes and Endogenous Estrogen Exposure on Female Breast Cancer Risk
Article
  • Mar 2010
  • ANN SURG ONCOL
Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damage by means of repair enzymes. Genotypic variants of DNA damage repair genes, participating in base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer. In a hospital-based case-control study of female breast cancer, DNA samples were obtained from 401 cases and 533 enrolled healthy controls, all of whom were Chinese women in Taiwan. Genotyping of polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2 Lys751Gln, ERCC4 Ser662Pro, and ERCC5 His1104Asp was performed and used to evaluate breast cancer susceptibility. Of the nonsynonymous polymorphisms, the ERCC5 1104Asp variant was significantly associated with breast cancer (odds ratio = 1.42; 95% confidence interval = 1.08-1.97), and this association was more pronounced in women with lengthy estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (P(trend) = .038). The synergistic effect of multiple genes on the increase of risk was significant in women with a longer period of estrogen exposure (>26 years), greater age at first full-term pregnancy (>26 years), a longer menarche-to-first full-term pregnancy interval (>11 years), and higher body mass index (>22) (all P<.05). This study demonstrates that genotype polymorphisms related to DNA damage repair confer greater susceptibility to endogenous estrogen in the development of breast cancer in women.
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The Global Breast Cancer Burden: Variations in Epidemiology and Survival
Article
  • Jan 2006
Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care. We review recent breast cancer incidence and mortality statistics and explore why these vary so greatly across the world. Further research is needed to fully understand the reasons for variations in breast cancer outcomes. This will aid the development of tailored strategies to improve outcomes in general as well as the standard of care for underserved populations and reduce the burden of breast cancer worldwide.
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Westernizing” Women’s Risks?” Breast Cancer in Lower-Income Countries
Article
  • Feb 2008
  • NEW ENGL J MED
Some 45% of the new cases of breast cancer diagnosed each year, and more than 55% of breast-cancer–related deaths, occur in low- and middle-income countries. Dr. Peggy Porter writes that the most widely cited reason for the global increase in breast cancer is the “Westernization” of the developing world. Dr. Peggy Porter discusses the increasing incidence of breast cancer in lower-income countries and the need for improved data, awareness, screening, and standards of care. Dr. Porter is a cancer biology researcher at the Fred Hutchinson Cancer Research Center and a professor of pathology at the University of Washington School of Medicine, Seattle.
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