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首页> 外文期刊>Cancer genetics and cytogenetics >A MLH1 polymorphism that increases cancer risk is associated with better outcome in sporadic colorectal cancer.
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A MLH1 polymorphism that increases cancer risk is associated with better outcome in sporadic colorectal cancer.

机译：MLH1多态性会增加癌症风险，在散发性结直肠癌中具有更好的预后。

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Germline mutations or the malfunctioning of postreplicative mismatch repair genes (MMR) are responsible of hereditary nonpolyposis colorectal cancer (HNPCC), and are also implied in some sporadic colorectal cancer (CRC) forms without any familial history of this disease. Besides germinal mutations and methylation, single-nucleotide polymorphisms (SNP) can predispose to nonfamilial CRC with low to moderate penetrance. In this case-control study, we analyzed three MLH1 single-nucleotide polymorphisms (exon 5: 415G-->C, rs28930073; exon 8: 655A-->G, rs1799977 and exon 16: 1852-1853AA-->GC) in 140 sporadic colorectal cancer cases and 125 healthy individuals to evaluate the relationship among CRC risk and clinicopathologic and genetic characteristics of the tumors. In our study, no 415G-->C variant carrier was found among all analyzed samples. The 1852-1853AA-->GC is a rare variant detected in heterozygoses in five controls and one case. In relation to the more frequent 655A-->G polymorphism, association analyses revealed that G carriers (AG or GG genotype) displayed a higher risk of CRC compared with AA homozygous [odds ratio (OR) AG=2.55, 95% confidence interval (CI)=1.48-4.39; P=0.01 and OR GG=2.48, 95% CI=1.20-5.11; P=0.01, respectively]. G-carrier males showed high CRC risk compared with homozygous AA wild-type individuals (OR: AG=3.05; 95% CI=1.49-6.26, P=0.002; OR: GG=3.60; 95% CI=1.29-10.03). Nevertheless, patients carrying the G allele displayed a better outcome than wild-type genotype carriers (log rank=7.26; P=0.007) and did not present vascular invasion (P=0.03), distant metastasis (P=0.004), or recurrence (P=0.01). MLH1 655A-->G change is associated with an increased risk, although it seems to have a favorable effect on patients, providing a better outcome. Moreover, our results suggest that for genomic profiling to predict the clinical outcome of patients with colorectal cancer, gender must also be considered.
机译：生殖系突变或复制后错配修复基因（MMR）的功能异常是遗传性非息肉性结直肠癌（HNPCC）的原因，并且也隐含在一些散发性结直肠癌（CRC）形式中，而没有这种疾病的家族史。除生发突变和甲基化外，单核苷酸多态性（SNP）还可导致低家族性和低外显性的非家族性CRC。在本病例对照研究中，我们分析了MLH1的三种单核苷酸多态性（外显子5：415G-> C，rs28930073;外显子8：655A-> G，rs1799977和外显子16：1852-1853AA-> GC）。评估140例散发性结直肠癌病例和125例健康个体，以评估CRC风险与肿瘤临床病理和遗传特征之间的关系。在我们的研究中，所有分析样品中均未发现415G-> C变异载体。 1852-1853AA-> GC是在5个对照和1个病例的杂合子中检测到的罕见变体。关于较频繁的655A-> G多态性，关联分析显示，与AA纯合性[比值比（OR）AG = 2.55，95％置信区间（OR）相比，G携带者（AG或GG基因型）显示出更高的CRC风险。 CI）= 1.48-4.39; P = 0.01且OR GG = 2.48，95％CI = 1.20-5.11; P分别为0.01]。与纯合AA野生型个体相比，G携带者男性表现出较高的CRC风险（OR：AG = 3.05; 95％CI = 1.49-6.26，P = 0.002; OR：GG = 3.60; 95％CI = 1.29-10.03）。然而，携带G等位基因的患者比野生型基因型携带者表现出更好的预后（log rank = 7.26; P = 0.007），并且没有血管侵犯（P = 0.03），远处转移（P = 0.004）或复发（ P ＝ 0.01）。 MLH1 655A-> G的变化与风险增加有关，尽管它似乎对患者产生有利的影响，提供了更好的结果。此外，我们的结果表明，要进行基因组图谱预测大肠癌患者的临床结局，还必须考虑性别。

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