title: Adipokine genes and prostate cancer risk.
abstract: Adiposity and adipocyte-derived cytokines have been implicated in prostate carcinogenesis. However, the relationship of adipokine gene variants with prostate cancer risk has not been thoroughly investigated. We therefore examined common variants of the IL6, LEP, LEPR, TNF and ADIPOQ genes in relation to prostate cancer in a case-control study nested within a large cohort of Finnish men. The study sample consisted of 1,053 cases of prostate cancer, diagnosed over an average 11 years of follow up, and 1,053 controls matched to the cases on age, intervention group and date of baseline blood draw. Logistic regression was used to model the relative odds of prostate cancer. We also examined genotypes in relation to serum insulin, IGF-1 and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (-14858A>G, -13973A>C, -13736C>A) in a potential regulatory region of the LEP gene conferred a statistically significant 20% reduced risk of prostate cancer. For example, at the -14858A>G locus, heterozygotes and homozygotes for the A allele had an odds ratio (OR) of prostate cancer of 0.76 [95% confidence interval (CI) 0.62, 0.93] and 0.79 (95% CI 0.60, 1.04), respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; 95% CI 0.99,1.67; p(trend) = 0.05). Polymorphisms in the IL6, LEPR, TNF and ADIPOQ genes were not associated with prostate cancer. Allelic variants in the LEP gene are related to prostate cancer risk, supporting a role for leptin in prostate carcinogenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. moorest@mail.nih.gov
authors.forename: Steven C
authors.initials: SC
authors.lastname: Moore
authors.forename: Michael F
authors.initials: MF
authors.lastname: Leitzmann
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Kirk
authors.initials: K
authors.lastname: Snyder
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.forename: Susan T
authors.initials: ST
authors.lastname: Mayne
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D005387:Finland; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D054411:Receptors, Leptin / Q000378:metabolism*; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I