Abstract
BackgroundA cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer.MethodsAmong participants in an ongoing cohort study, 1438 Caucasian women had a breast biopsy for BBD and were successfully genotyped for at least one of the polymorphisms examined in this study. Genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003 were identified through cancer registries.ResultsAmong all participants, the ESR2 *5772G allele was associated with a significant decrease in the risk of breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally significant associations with the development of breast cancer were observed between carriers of the variant ESR1 – 104062T allele (OR 0.70, 95% CI 0.45, 1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32).ConclusionThe results indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play a role in progression of BBD to breast cancer among Caucasian women. Although additional studies are needed to confirm or refute our findings, these results suggest that genetic markers may aid in the identification of women who are at risk for progression of BBD to cancer.
Highlights
A cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer
The aim of the present study was to analyze the associations between genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) and the risk of developing breast cancer among women with BBD
All of the polymorphisms examined were in Hardy-Weinberg equilibrium among women not developing breast cancer, with the exception of the CYP1B1 Ile462Val polymorphism (p-value = 0.02)
Summary
A cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer. Biopsy-proven benign breast disease (BBD) is a welldefined risk factor for developing invasive breast cancer [1,2]. A woman's level of endogenous estrogen may be important in the progression of BBD to invasive breast cancer. Abundant evidence suggests that estrogen is an important factor in the development of breast cancer among average-risk women. This evidence includes findings from recent prospective studies that showed significantly increased levels of serum estrogen in women who developed breast cancer compared to women who did not develop breast cancer [3,4,5,6,7]. Numerous studies have reported that risk factors associated with prolonged estrogen exposure, such as early age at menarche, nulliparity, and older age at first birth, increase a woman's risk of developing breast cancer (reviewed by Mitrunen and Hirvonen [8])
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