Polymorphisms in CYP19A1, HSD17B1 and HSD17B2 genes and serum sex hormone level among postmenopausal Japanese women

• Several CYP19A1 and HSD17B2 genotypes affect serum estrone and estradiol level.
• The effect of these polymorphisms is independent of current BMI.
• They might be associated with the etiology of estrogen-dependent cancer.
• The strength of this study is its large sample size.
• Our results may be widely generalizable for postmenopausal Japanese women.

ObjectiveExtraovarian sex hormone production plays an important role in estrogen biosynthesis in postmenopausal women. We examined possible associations between serum sex hormone level and polymorphisms in CYP19A1, HSD17B1, and HSD17B2. We also assessed possible interaction between these polymorphisms and current overweight.MethodsWe conducted a cross-sectional study. 785 Japanese natural postmenopausal women were randomly selected from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study database. Information on lifestyle factors was obtained from a self-administered questionnaire. Serum estrogens and androgens levels were measured by liquid chromatography–tandem mass spectrometry. Four tag SNPs (single nucleotide polymorphisms) of CYP19A1, one missense SNP of HSD17B1 and three tag SNPs of HSD17B2 were examined by Invader assay. A trend test was conducted using linear regression.ResultsAfter adjustment for multiple comparisons, we found that rs4441215 and rs936306 in CYP19A1 and rs4888202 and rs2955160 in HSD17B2 were associated with differences in serum estrone level. Further, rs4441215 and rs936306 were associated with differences in serum estradiol level. None of these polymorphisms showed a significant interaction with current body mass index (BMI).ConclusionsOur findings suggested that CYP19A1 and HSD17B2 polymorphisms might be associated with circulating sex hormone levels in Japanese postmenopausal women, independent of current BMI.