Pairwise Combinations of Estrogen Metabolism Genotypes in Postmenopausal Breast Cancer Etiology

Abstract

Estrogen exposures have been associated with breast cancer risk, and genes involved in estrogen metabolism have been reported to mediate that risk. Our goal was to better understand whether combinations of candidate estrogen metabolism genotypes are associated with breast cancer etiology. A population-based case-control study in three counties of the Philadelphia Metropolitan area was undertaken. We evaluated seven main effects and 21 first-order interactions in African Americans and European Americans for genotypes at COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, SULT1A1, and SULT1E1 in 878 breast cancer cases and 1,409 matched random digit -dialed controls. In European Americans, we observed main effect associations of genotypes containing any CYP1A1*2C (odds ratio, 1.71; 95% confidence interval, 1.09-2.67) and breast cancer. No significant main effects were observed in African Americans. Three significant first-order interactions were observed. In European Americans, interactions between SULT1A1*2 and CYP1A1*2C genotypes (P interaction < 0.001) and between SULT1E1 and CYP1A2*1F genotypes were observed (P interaction = 0.006). In African Americans, an interaction between SULT1A1*2 and CYP1B1*4 was observed (P interaction = 0.041). We applied the false-positive report probability approach, which suggested that these associations were noteworthy; however, we cannot rule out the possibility that chance led to these associations. Pending future confirmation of these results, our data suggest that breast cancer etiology in both European American and African American postmenopausal women may involve the interaction of a gene responsible for the generation of catecholestrogens with a gene involved in estrogen and catecholestrogen sulfation. (Cancer Epidemiol Biomarkers Prev 2007;16(3):444 -50)

Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

“…In two other studies, Long et al and Rebbeck et al reported that the CYP1A2*F genotype was not associated with breast cancer risk. 25,26 In spite of the hypothesis based on in vitro enzymatic activity, our results showed that the CC genotype is associated with increased rather than decreased breast cancer risk (OR 5 2.75, 95% CI 1.47-5.14). Moreover, the SNPs remained significant in the dominant model even after multiple testing using Bonferroni correction (adjusted p-value: 0.04, OR 5 2.74, 95% CI 1.47-5.10).…”

Genetic polymorphisms in estrogen metabolism and breast cancer risk in case–control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians

“…14,[30][31][32][33] Findings have been inconsistent, however, showing no association for Chinese, 30 Caucasian 31 or American-African women; 31 a positive association for Russian women; 33 and an inverse association for a multiethnic group (Multiethnic Cohort Study). 14 In the present study, we found a significantly decreased risk among NJB with the CC genotype of CYP1A2*1F.…”

Lack of Effect Modification between Estrogen Metabolism Genotypes and Combined Hormone Replacement Therapy in Postmenopausal Breast Cancer Risk

“…The Women's Insights and Shared Experiences (WISE) study is a population-based case-control study that consisted of an efficient sampling design using shared controls to compare both breast cancer cases and endometrial cancer cases (11,12). Incident breast cancer cases were identified through hospitals and the Pennsylvania State Cancer Registry, and frequency-matched controls were identified from the community using random-digit dialing.…”

“…Genetic variants in COMT, CYP1A1, CYP1A2, CYP1B1, SULT1A1, and SULT1E1 were assayed as previously described (13). Additional details of our study design, which included ascertainment of both breast and endometrial cancer cases and matched controls, have been previously reported (11)(12)(13)(14).…”

“…Genetic variants in COMT, CYP1A1, CYP1A2, CYP1B1, SULT1A1, and SULT1E1 were assayed as previously described (13). Additional details of our study design, which included ascertainment of both breast and endometrial cancer cases and matched controls, have been previously reported (11)(12)(13)(14).Odds ratio (OR) estimates and 95% confidence intervals were calculated to evaluate the relationship between hormone metabolism genes and hormone use with breast cancer risk. Using multiple conditional logistic regression, we adjusted for (a) education (<high school, high school graduate, more than high school but not a college graduate, college graduate or higher); (b) body mass index during the participant's 40's; (c) number of full-term pregnancies (0, 1, 2, 3+); (d) years of menses; (e) menopause type (known natural, assumed natural at reference age of 50 if menopausal status is unknown, and induced); (f) never/former/current smoker  years of smoking; and (g) oral contraceptive use (never, <3 years, 3 years or more).…”