Age‐specific association of steroid hormone pathway gene polymorphisms with breast cancer risk

Abstract

BACKGROUNDBreast cancer (BC) is a complex disease, and the incidence rates for BC increase with age. Both environmental factors and genetics have an impact on the risk of BC. Although the effects of environmental factors may vary with age, it has been assumed generally that the penetrance of single nucleotide polymorphisms (SNPs) is constant throughout life. In the current study, the results demonstrated that certain SNPs exhibit BC risk associations that vary considerably with age.METHODSSNPs in 12 steroid hormone pathway genes were investigated for associations with BC risk in white women who were enrolled in an age‐matched, case‐control (1:2 for cases and controls, respectively) study that consisted of a discovery set (n = 5000 women) and an independent validation set (n = 1583 women).RESULTSSignificant age‐related trends were identified and confirmed for SNPs in 4 genes associated with BC risk. The cytosine/cytosine (C/C) genotype of cytochrome P450 XIB2 (CYP11B2) was associated with decreased risk at younger ages (ages 30–44 years) but an increased risk at older ages (ages 55–69 years). The homozygous cytosine‐guanine (CG/CG) genotype of uridine phosphorylase glycosyltransferase 1A7 (UGT1A7) was associated with increased risk at younger ages but decreased risk at older ages. Associations in cytochrome P450 19 (CYP19) and progesterone receptor (PGR) were confined to middle age (ages 45–54 years).CONCLUSIONSThe identification of age‐specific genetic associations may have profound implications for future etiologic studies of BC and for the use of SNP genotyping to accurately predict the risk of BC in women. Cancer 2007. © 2007 American Cancer Society.

No association between a progesterone receptor gene promoter polymorphism (+331G>A) and breast cancer risk in Caucasian women: evidence from a literature-based meta-analysis

“…De Vivo's team reported two investigations from the same study population [19,26], and we here included the one with the largest sample numbers [26]. Of note, besides the 11 studies, one more study reported by Ralph et al [31] was not included into analysis since the genotyping data of ?331G[A was unavailable, although the authors declared that those data as supplemental material could be obtained at their website. As a result, there were 10 publications containing 13,702 cases and 14,726 controls entering into the subsequent meta-analysis.…”

Lack of association between catechol-O-methyltransferase Val108/158Met polymorphism and breast cancer risk: a meta-analysis of 25,627 cases and 34,222 controls

“…First, some studies found significant associations between COMT Val108/158Met polymorphism and breast cancer risk in several subgroups of populations, such as associations among postmenopausal women with a low body mass index (BMI) [10,15], a high BMI [8], or women at young ages [15,39]. It is difficult for a metaanalysis to derive such specific associations because the results from previous studies were not presented in a uniform standard.…”

Polymorphisms of UGT1A7 and XRCC1 are associated with an increased risk of hepatocellular carcinoma in Northeast China

“…Polymorphisms of UGT1A7 could alter the enzymatic activity of the encoded protein [7] and have been reported to be involved in colorectal cancer [20][21][22][23] , lung cancer [24,25] , breast cancer [26] , pancreatic cancer [27] and HCC [9,11,28] . Vogel et al [9] first reported that UGT1A7 * 3 allele could significantly increase HCC risk but Stucker et al [12] found that the association existed only when the case group was restricted to the viral origin.…”