MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

Xu, Jiali; Yin, Zhiqiang; Huang, Ming‐De; Wang, Xiefeng; Gao, Wen; Liu, Lingxiang; Wang, Rongsheng; Pu-wen, Huang; Yin, Yongmei; Liu, Ping; Shu, Yongqian

doi:10.7314/apjcp.2012.13.3.901

Cited by 8 publications

(6 citation statements)

References 61 publications

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“…Our results need to be confirmed by randomized prospective studies. Second, ethnic differences have been observed for some MMR genotype frequencies [20], and future studies in other countries may show some different results from ours. In addition, the intestinal and diffuse subtypes, frequently exhibiting marked differences, were unavailable in our data.…”

Section: Discussioncontrasting

confidence: 81%

“…Furthermore, some genetic defects may impact MMR function or activity other than MMR protein expression level [15]. Specifically, common polymorphisms of MMR genes with a low-penetrant effect that may be also insufficient to induce MSI can cause heterogeneous MMR capability among individuals, which correlates with cancer risk and clinical outcome [16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

“…The rs1800734 A-allele has a lower binding affinity for transcription factors and an increased risk of hypermethylation for the MLH1 promoter than the G-allele, and therefore is associated with morbidity of many cancers [19,20]. The rs2303428 and rs3732183 polymorphisms may impact the alternative splicing of MSH2 mRNA to increase cancer risk [16][17][18][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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A polymorphism within the mismatch repair gene predicts prognosis and adjuvant chemotherapy benefit in gastric cancer

Zhao

Dai

et al. 2019

Gastric Cancer

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Background Defective mismatch repair (dMMR) and microsatellite instability (MSI) correlate with gastric cancer (GC) outcome. We hypothesized that MMR genetic polymorphisms that have low-penetrant effects but may cause heterogeneous MMR capability among individuals also affect GC outcome. Methods The polymorphisms rs1800734 in MLH1, rs2303428 and rs3732183 in MSH2, rs735943 in EXO1, and rs11797 in TREX1 were selected and analyzed in independent discovery and validation sets that included 167 and 593 patients, respectively. MSI was determined. Results In both the discovery and validation sets, the rs2303428 TC + CC genotype correlated with poor overall survival (OS) in non-cardia (P < 0.05) but not in cardia GC. Multivariate models showed that for OS of patients with non-cardia GC, the rs2303428 TC + CC genotype was an independent predictor in the validation set (HR 1.54; 95% CI 1.02-2.32; P = 0.040) and had a trend to be an independent predictor in the discovery set (HR 1.70; 95% CI 0.96-3.01; P = 0.067). Furthermore, in both patient sets, fluoropyrimidines-based adjuvant chemotherapy improved OS for non-cardia patients with the rs2303428 TC + CC genotype (HR 0.14; 95% CI 0.04-0.57; P = 0.006; and HR 0.29; 95% CI 0.15-0.58; P < 0.001, respectively) but not for those with the TT genotype. The rs2303428 genotypes were not associated with MSI frequency. The rs2303428 TC + CC genotype correlated with reduced expressions for thymidylate synthetase, P-glycoprotein and ERCC1 (P < 0.05) in non-cardia GC. Conclusions The rs2303428 genotypes may predict prognosis and adjuvant chemotherapy benefit in non-cardia GC patients.

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Section: Discussioncontrasting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A polymorphism within the mismatch repair gene predicts prognosis and adjuvant chemotherapy benefit in gastric cancer

Zhao

Dai

et al. 2019

Gastric Cancer

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“…Although three similar meta-analyses have reported the existence of an association between the MLH1 -93G>A polymorphism and the risk of CRC [22], [28], [29], they showed some different results. For instance, Whiffin et al reported the pooled effect on the -93G>A polymorphism and CRC based on five case-control studies with a total of 14,121 CRC cases and 10,890 controls [22].…”

Section: Discussionmentioning

confidence: 96%

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Wang

Liu

et al. 2012

PLoS ONE

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BackgroundThe -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.ObjectiveThe aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.MethodsTo derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.ResultsThe overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.ConclusionOur results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.

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“…For example, the MLH1 -93G>A SNP (rs1800734) is located in the promoter region that is responsible for maximal transcriptional activity of this gene[106],[107]. The association between the -93G>A SNP and cancer risk was investigated most in colorectal cancer[108],[109]. Reduced expression levels of MSH2 have been reported in hereditary nonpolyposis colon cancer (HNPCC) and some other human cancers[110]–[113].…”

Section: The Mmr Pathwaymentioning

confidence: 99%

Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

et al. 2013

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Although tobacco and alcohol consumption are two common risk factors of head and neck cancer (HNC), other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Human DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic variants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms (SNPs) in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly increased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus interactions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway-based analyses of DNA repair genes derived from genome-wide association studies (GWASs) in HNC are needed.

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MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

Cited by 8 publications

References 61 publications

A polymorphism within the mismatch repair gene predicts prognosis and adjuvant chemotherapy benefit in gastric cancer

A polymorphism within the mismatch repair gene predicts prognosis and adjuvant chemotherapy benefit in gastric cancer

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

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