Danforth Kim N, Hayes Richard B, Rodriguez Carmen, Yu Kai, Sakoda Lori C, Huang Wen-Yi, Chen Bingshu E, Chen Jinbo, Andriole Gerald L, Calle Eugenia E, Jacobs Eric J, Chu Lisa W, Figueroa Jonine D, Yeager Meredith, Platz Elizabeth A, Michaud Dominique S, Chanock Stephen J, Thun Michael J, Hsing Ann W
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852, USA.
Carcinogenesis. 2008 Mar;29(3):568-72. doi: 10.1093/carcin/bgm253. Epub 2007 Nov 13.
Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the proinflammatory cyclooxygenase 2 enzyme believed to be the rate-limiting step in the synthesis of prostaglandins, important mediators of inflammation. We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275 and rs689470) were examined in SNP and haplotype analyses (five SNPs in PLCO and four SNPs in the Nutrition Cohort). In PLCO, the Ex10 +837 T>C marker (rs5275) was initially associated with prostate cancer risk (P-trend = 0.02) but became non-significant after adjustment for multiple comparisons (P = 0.08); this SNP showed no association with prostate cancer risk in the Nutrition Cohort (P-trend = 0.54) or in an analysis pooling the two cohorts (P-trend = 0.20). No other SNP was associated with prostate cancer risk in PLCO or the Nutrition Cohort individually or combined. Haplotype analyses suggested an association between PTGS2 variants in PLCO alone (global P = 0.007), but not in the Nutrition Cohort (global P = 0.78) or pooled analysis (global P = 0.18). In conclusion, despite the potential importance of inflammation in prostate carcinogenesis, results from our large study of five PTGS2 SNPs does not support a strong association between PTGS2 variants and prostate cancer risk in non-Hispanic white men.
慢性炎症被认为会增加患前列腺癌的风险。前列腺素内过氧化物合酶2（PTGS2）编码促炎环氧化酶2，该酶被认为是前列腺素合成中的限速步骤，而前列腺素是炎症的重要介质。在两项大型病例对照研究中，我们调查了2321例前列腺癌病例和2560例对照中PTGS2基因多态性与前列腺癌风险之间的关联，这两项研究嵌套于前列腺、肺、结肠和卵巢（PLCO）癌症筛查试验以及癌症预防研究II营养队列中。在单核苷酸多态性（SNP）和单倍型分析中检测了五个单核苷酸多态性（SNP）（rs5277、rs20432、rs4648276、rs5275和rs689470）（PLCO中有五个SNP，营养队列中有四个SNP）。在PLCO中，Ex10 +837 T>C标记（rs5275）最初与前列腺癌风险相关（P趋势=0.02），但在进行多重比较校正后变得不显著（P = 0.08）；该SNP在营养队列中与前列腺癌风险无关联（P趋势=0.54），在合并两个队列的分析中也无关联（P趋势=0.20）。在PLCO或营养队列中，单独或合并分析时，没有其他SNP与前列腺癌风险相关。单倍型分析表明，仅在PLCO中PTGS2变异与前列腺癌有关联（总体P = 0.007），但在营养队列中无关联（总体P = 0.78），在合并分析中也无关联（总体P = 0.18）。总之，尽管炎症在前列腺癌发生中可能具有重要意义，但我们对五个PTGS2 SNP的大型研究结果并不支持PTGS2变异与非西班牙裔白人男性前列腺癌风险之间存在强关联。
