title: The association between inflammation-related genes and serum androgen levels in men: the prostate, lung, colorectal, and ovarian study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20852, USA. tamra.e.meyer@us.army.mil
authors.forename: Tamra E
authors.initials: TE
authors.lastname: Meyer
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Chu
authors.forename: Qizhai
authors.initials: Q
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Idan
authors.initials: I
authors.lastname: Menashe
authors.forename: Anand P
authors.initials: AP
authors.lastname: Chokkalingam
authors.forename: Sabah M
authors.initials: SM
authors.lastname: Quraishi
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Weiss
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
mesh_terms: D000368:Aged; D000483:Alleles; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D016022:Case-Control Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D013739:Testosterone; D000735:Androstenedione