Genetic Variation in Steroid and Xenobiotic Metabolizing Pathways and Enterolactone Excretion Before and After Flaxseed Intervention in African American and European American Women

Abstract

Metabolism and excretion of the phytoestrogen enterolactone (ENL), which has been associated with breast cancer risk, may be affected by variation in steroid hormone and xenobiotic metabolizing genes. We conducted a randomized, crossover flaxseed intervention study in 252 healthy, postmenopausal women (137 EA and 115 African Americans AA) from western New York. Participants were randomly assigned to maintain usual diet or consume 10 g/d ground flaxseed for 6 weeks. After a 2-month washout period, participants crossed over to the other diet condition for an additional 6 weeks. Urinary ENL excretion was measured by GC-MS and 70 polymorphisms in 29 genes related to steroid hormone and xenobiotic metabolism were genotyped. Mixed additive genetic models were constructed to examine association of genetic variation with urinary ENL excretion at baseline and after the flaxseed intervention. SNPs in several genes were nominally (p<0.05) associated with ENL excretion at baseline and/or after intervention: ESR1 , CYP1B1 , COMT , CYP3A5 , ARPC1A , BCL2L11 , SHBG , SLCO1B1 , and ZKSCAN5 . A greater number of SNPs were associated among AA women than among EA women, and no SNPs were associated in both races. No SNPs-ENL associations were statistically significant after correction for multiple comparisons. Variation in several genes related to steroid hormone metabolism was associated with lignan excretion at baseline and/or after flaxseed intervention among postmenopausal women. These findings may contribute to our understanding of the differences observed in urinary ENL excretion among AA and EA women and thus hormone related breast cancer risk.