Cancer Genetics Group, Children's Cancer Institute Australia for Medical Research, Sydney Children's Hospital, High St, Randwick, NSW, Australia.
BMC Cancer. 2010 Feb 25;10:69. doi: 10.1186/1471-2407-10-69.
Chronic inflammation is considered to be implicated in the development of prostate cancer. In this study we are the first to investigate a potential association between variants in an autoimmune related region on chromosome 4q27 and prostate cancer risk. This region harbors two cytokine genes IL-2 and the recently described IL-21.
We genotyped six variants previously associated with autoimmune disease (namely rs13151961, rs13119723, rs17388568, rs3136534, rs6822844 and rs6840978) and one functional IL-2 promoter variant (rs2069762) for possible association with prostate cancer risk using the Australian Risk Factors for Prostate Cancer case-control Study.
Overall, our results do not support an association between the seven variants at position 4q27 and prostate cancer risk. Per allele odds ratios (ORs) were not significantly different from 1 (all P-values = 0.06). However, we found suggestive evidence for a significant association between the presence of the rs13119723 variant (located in a protein of unknown function) and men with a family history of prostate cancer in first-degree relatives (P-value for interaction 0.02). The per allele OR associated with this variant was significantly higher than 1 (2.37; 95% C.I. = 1.01-5.57).
We suggest that genetic variation within the chromosome 4q27 locus might be associated with prostate cancer susceptibility in men with a family history of the disease. Furthermore, our study alludes to a potential role of unknown protein KIAA1109 in conferring this risk.
慢性炎症被认为与前列腺癌的发展有关。在这项研究中，我们首次研究了染色体 4q27 上与自身免疫相关区域的变异与前列腺癌风险之间的潜在关联。该区域包含两个细胞因子基因 IL-2 和最近描述的 IL-21。
我们对先前与自身免疫性疾病相关的六个变体（即 rs13151961、rs13119723、rs17388568、rs3136534、rs6822844 和 rs6840978）和一个功能性 IL-2 启动子变体（rs2069762）进行了基因分型，以评估它们与前列腺癌风险的关联，使用澳大利亚前列腺癌危险因素病例对照研究。
总体而言，我们的结果不支持 4q27 位置的七个变体与前列腺癌风险之间的关联。每个等位基因的比值比（OR）与 1 没有显著差异（所有 P 值=0.06）。然而，我们发现 rs13119723 变体（位于功能未知的蛋白质中）的存在与一级亲属中有前列腺癌家族史的男性之间存在显著关联的迹象（交互作用的 P 值为 0.02）。与该变体相关的每个等位基因的 OR 显著高于 1（2.37；95%置信区间为 1.01-5.57）。
我们认为，染色体 4q27 位点的遗传变异可能与有前列腺癌家族史的男性的前列腺癌易感性有关。此外，我们的研究暗示了未知蛋白 KIAA1109 可能在赋予这种风险方面发挥作用。
