title: Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk.
abstract: IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1alpha and IL1beta. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the 'ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR = 1.0, 95% CI = 0.8-1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3-2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.
authors.affiliation: Department of Radiation Sciences/Oncology, Umeå University, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Lindmark
authors.forename: S L
authors.initials: SL
authors.lastname: Zheng
authors.forename: F
authors.initials: F
authors.lastname: Wiklund
authors.forename: K A
authors.initials: KA
authors.lastname: Bälter
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: B
authors.initials: B
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Hedelin
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: J-E
authors.initials: JE
authors.lastname: Johansson
authors.forename: D A
authors.initials: DA
authors.lastname: Meyers
authors.forename: H-O
authors.initials: HO
authors.lastname: Adami
authors.forename: W
authors.initials: W
authors.lastname: Isaacs
authors.forename: H
authors.initials: H
authors.lastname: Grönberg
authors.forename: J
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics* / Q000502:physiology; D013548:Sweden
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins