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Age‐specific association of steroid hormone pathway gene polymorphisms with breast cancer risk
Author(s) -
Ralph David A.,
Zhao Lue Ping,
Aston Christopher E.,
Manjeshwar Sharmila,
Pugh Thomas W.,
DeFreese Daniele C.,
Gramling Bobby A.,
Shimasaki Craig D.,
Jupe Eldon R.
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22634
Subject(s) - medicine , breast cancer , hormone , association (psychology) , oncology , gene , steroid , endocrinology , bioinformatics , physiology , cancer , genetics , biology , philosophy , epistemology
BACKGROUND Breast 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. METHODS SNPs 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). RESULTS Significant 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). CONCLUSIONS The 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.