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The association between inflammation‐related genes and serum androgen levels in men: The prostate, lung, colorectal, and ovarian study
Author(s) -
Meyer Tamra E.,
Chu Lisa W.,
Li Qizhai,
Yu Kai,
Rosenberg Philip S.,
Menashe Idan,
Chokkalingam Anand P.,
Quraishi Sabah M.,
Huang WenYi,
Weiss Jocelyn M.,
Kaaks Rudolf,
Hayes Richard B.,
Chanock Stephen J.,
Hsing Ann W.
Publication year - 2012
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21407
Subject(s) - single nucleotide polymorphism , medicine , endocrinology , androgen , prostate cancer , biology , cancer , genotype , hormone , gene , genetics
Abstract BACKGROUND Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation‐related genes. METHODS In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation‐related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α‐androstane‐3α, 17β‐diol glucuronide [3αdiol G], and 4‐androstene‐3,17‐dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome‐wide scan. SNP‐hormone associations were evaluated using linear regression of hormones adjusted for age. Gene‐based P values were generated using an adaptive rank truncated product (ARTP) method. RESULTS Suggestive associations were observed for two inflammation‐related genes and circulating androgen levels (false discovery rate [FDR] q‐value <0.1) in both SNP and gene‐based tests. Specifically, T was associated with common variants in MMP2 and CD14 , with the most significant SNPs being rs893226G > T in MMP2 and rs3822356T > C in CD14 (FDR q‐value = 0.09 for both SNPs). Other genes implicated in either SNP or gene‐based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione. CONCLUSION These results suggest possible cross‐talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk. Prostate 72:65–71, 2012. © 2011 Wiley Periodicals, Inc.