Mismatch repair polymorphisms and the risk of colorectal cancer
Mismatch repair polymorphisms and the risk of colorectal cancer
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DOI：
10.1002/ijc.22510
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Helzlsouer, Kathy J.
中科院分区：
文献类型：
--
作者：
Berndt, Sonja I.;Platz, Elizabeth A.;Helzlsouer, Kathy J.
错配修复基因中罕见的种系变异与遗传性非息肉病性结直肠癌有关;然而，这些基因中常见的多态性是否会改变结直肠癌的风险尚不清楚。为了研究错配修复基因中常见变异与结直肠癌之间的关联，我们在CLUE 11队列中进行了一项病例队列研究。在237例结直肠癌病例和2,189名参与者的子队列中，对3个错配修复基因（MSH 3 R940 Q、MSH 3 T1036 A、MSH 6 G39 E和MLH 1 1219 V）的4个单核苷酸多态性进行了基因分型。估计每种多态性的发生率比（RR）和95%置信区间（95% CI）。发现MSH 3 1036 A变体与结直肠癌风险增加相关（AT和TT基因型分别为RR = 1.28，95% CI：0.94-1.74和RR = 1.65，95% CI：1.01-2.70，P趋势= 0.02），特别是近端结肠癌。尽管MSH 3 940 Q变异体与结直肠癌总体相关性较弱，（P趋势= 0.07），与近端结肠癌风险显著增加相关（RQ和QQ基因型的RR = 1.69，95%CI：1.10-2.61和RR = 2.68，95%CI：0.96-7.47，P趋势= 0.005）。加工肉类的摄入似乎改变了MSH 3多态性与结直肠癌之间的关联（两者的P-相互作用< 0-10）。未观察到与MSH 6和MLH 1多态性的整体关联。这项研究表明，错配修复基因MSH 3的常见多态性可能会增加结直肠癌，特别是近端结肠癌的风险。(c)2007 Wiley-Liss，Inc.
Rare germline variants in mismatch repair genes have been linked to hereditary nonpolyposis colorectal cancer; however, it is unknown whether common polymorphisms in these genes alter the risk of colorectal cancer. To examine the association between common variants in mismatch repair genes and colorectal cancer, we conducted a case-cohort study within the CLUE 11 cohort. Four single nucleotide polymorphisms in 3 mismatch repair genes (MSH3 R940Q, MSH3 T1036A, MSH6 G39E and MLH1 1219V) were genotyped in 237 colorectal cancer cases and a subcohort of 2,189 participants. Incidence rate ratios (RRs) and 95% confidence intervals (95% CIs) for each polymorphism were estimated. The MSH3 1036A variant was found to be associated with an increased risk of colorectal cancer (RR = 1.28, 95% CI: 0.94-1.74 and RR = 1.65, 95% CI: 1.01-2.70 for the AT and TT genotypes, respectively, with P-trend = 0.02), particularly proximal colon cancer. Although the MSH3 940Q variant was only weakly associated with colorectal cancer overall (P-trend = 0.07), it was associated with a significant increased risk of proximal colon cancer (RR = 1.69, 95% CI: 1.10-2.61 and RR = 2.68, 95% CI: 0.96-7.47 for the RQ and QQ genotypes, respectively with P-trend = 0.005). Processed meat intake appeared to modify the association between the MSH3 polymorphisms and colorectal cancer (P-interaction < 0-10 for both). No association was observed with the MSH6 and MLH1 polymorphisms overall. This study suggests that common polymorphisms in the mismatch repair gene, MSH3, may increase the risk of colorectal cancer, especially proximal colon cancer. (c) 2007 Wiley-Liss, Inc.