Polymorphisms in Genes Involved in Sex Hormone Metabolism, Estrogen Plus Progestin Hormone Therapy Use, and Risk of Postmenopausal Breast Cancer

Abstract

Hormone therapy, estrogen plus progestin (E+P) particularly, is associated with increased risk of breast cancer. Functionally relevant polymorphisms in genes involved in sex hormone metabolism may alter exposure to exogenous sex hormones and affect risk of postmenopausal breast cancer. We evaluated associations of common polymorphisms in genes involved in estrogen and/or progesterone metabolism, E+P use, and their interactions with breast cancer risk in a case-control study of postmenopausal women (324 cases; 651 controls) nested within the VITAL cohort. None of the polymorphisms studied was, by itself, statistically significantly associated with breast cancer risk. E+P use was significantly associated with increased breast cancer risk (z10 years versus never; odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P trend = 0.0002). Statistically significant interactions between CYP1A1 Ile

Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a meta-analysis

“…As a result, given that the vast majority of data came from Caucasian populations in this meta-analysis, the results may not be safely extrapolated upon Chinese subjects. Similarly, no subanalysis pertaining to menopausal status was feasible, as solely a small subset of studies provided the relevant specific data [9,32,35].…”

“…Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls) [9,22,23,[28][29][30][31][32][33]; 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls) [9,22,23,28,31,[34][35][36][37][38]; 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls) [22, 29-32, 35, 39-43].…”

“…Specifically, the pooled ORs were as follows: 0.908 (0.761-1.084, random effects) for heterozygous carriers, 0.762 (0.522-1.112, random effects) for homozygous carriers, 0.905 (0.762-1.074, random effects) for the dominant model and 0.892 (0.688-1.157, random effects) for the recessive model. Worthy of note, the deviation from HWE could not be assessed due to reporting reasons in one study [32].…”

“…It is worth mentioning, however, that in one study [32] the deviation from HWE could not be assessed due to reporting reasons, i.e. categories of genotypes merged in the individual studies.…”

Does race modify the association between CYP1B1 Val432Leu polymorphism and breast cancer risk? A critical appraisal of a recent meta-analysis

“…Adopting the same search strategy and end-of-search date as Yao et al [1], we have located three relevant case-control studies in MEDLINE with a total number of 685 breast cancer cases and 931 controls, which have not been included in the meta-analysis [2][3][4]. Of note, all three casecontrol studies were performed on Caucasian populations.…”