Cancer Causes Control. 2013 Dec;24(12):2059-75. doi: 10.1007/s10552-013-0282-1.
Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and COX-2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy.
We genotyped candidate polymorphisms and tag SNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case–control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n = 1,470 cases/1,837 controls) and rectal cancer (n = 583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n = 959/1,535, rectal n = 505/839).
In PTGS2, a functional polymorphism (-765G[C; rs20417) was associated with a twofold increased rectal cancer risk (p = 0.05) in the DALS. This association replicated with a significant nearly fivefold increased risk of rectal cancer in the CCFR study (ORCC vs. GG = 4.88; 95 % CI 1.54–15.45; ORGC vs. GG = 1.36; 95 %CI 0.95–1.94). Genotype–NSAID interactions were observed in the DALS for PTGS1 and rectal cancer risk and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed.
非甾体抗炎药（NSAIDs）靶向前列腺素 H 合酶酶，环氧化酶（COX）-1 和 COX-2，并降低结直肠癌风险。这些酶编码基因的遗传变异可能与结肠癌和直肠癌风险以及 NSAID 疗效的变化相关。
我们在基于人群的病例对照研究（饮食、活动和生活方式研究，DALS）中对 PTGS1（COX-1）和 PTGS2（COX-2）中的候选多态性和标签 SNP 进行了基因分型，该研究包括结肠癌（n=1470 例/1837 例对照）和直肠癌（n=583/775），并在结肠癌家族登记处（CCFR；n=959/1535，n=505/839）的病例和对照中进行了独立分析。
在 PTGS2 中，一个功能多态性（-765G[C；rs20417）与 DALS 中直肠癌症风险增加两倍相关（p=0.05）。该关联在 CCFR 研究中得到了复制，直肠癌风险显著增加近五倍（ORCC vs. GG=4.88；95%CI 1.54-15.45；ORGC vs. GG=1.36；95%CI 0.95-1.94）。在 DALS 中观察到 PTGS1 和直肠癌风险以及 PTGS2 和结肠癌风险之间存在基因型-NSAID 相互作用，但在进行多次比较校正后不再显著，并且在 CCFR 中未得到复制。在 DALS 中未观察到 PTGS1 多态性与结肠癌或直肠癌风险之间存在显著相关性。
