The association between MLH1 -93 G&gt;A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis

Pan, Xue; Yang, Wei; Xu, Gaixia; Bai, Peng; Qin, Haojie; Zhang, Lushun; Zhai, Xiandun; Tang, Ming; Deng, Wei; Zhang, Lin; Gao, Linbo

doi:10.1093/mutage/ger032

Cited by 13 publications

(10 citation statements)

References 53 publications

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“…The finding that there was no statistically significant relationship between MLH1 À93G>A polymorphism and the total number of colorectal tumours is in line with previously published meta-analyses [7,9]. Nevertheless, the aim of our study was to analyse whether this polymorphism is associated with familial colorectal cancer which complied with the Amsterdam or Bethesda criteria, or whether it was related to sporadic colorectal cancer.…”

Section: Discussionsupporting

confidence: 82%

Incidence of −93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer

et al. 2013

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Aim The MLH1 promoter contains a common single nucleotide polymorphism (−93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 −93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects. Method We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed. Results The GA genotype was under‐represented in patients with familial colon cancer, whereas the AA genotype was over‐represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti‐MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI. Conclusion There is a relationship between the MLH1 −93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 −93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.

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Section: Discussionsupporting

confidence: 82%

Incidence of −93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer

et al. 2013

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“…In a recent meta-analysis study, no association with CRC was observed (Pan et al, 2011). However, Allan et al (2008) reported that MLH1 -93A was associated with a 3-fold increased risk of CRC, negative for the MLH1 protein detectable by immunohistochemistry (OR = 3.30, 95%CI = 1.46-7.47), while Raptis et al (2007) documented a 3-fold increased risk (P < 0.001) of CRC with MSI-H (microsatellite instability high) in a population from Ontario (OR = 3.23, 95%CI = 1.65-6.30) and an 8-fold increased risk (P < 0.001) in Newfoundland people (OR = 8.88, 95%CI = 2.33-33.9).…”

Section: Discussionmentioning

confidence: 91%

MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer

Muñiz-Mendoza¹,

Ml²,

Partida-Pérez³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. DNA repair proteins maintain DNA integrity; polymorphisms in genes coding for these proteins can increase susceptibility to colorectal cancer (CRC) development. We analyzed a possible association of MLH1 -93G>A and 655A>G and XRCC1 Arg194Trp and Arg399Gln polymorphisms with CRC in Mexican patients. Genomic DNA samples were obtained from peripheral blood of 108 individuals with CRC (study group) at diagnosis and 120 blood donors (control group) from Western Mexico; both groups ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 2315-2320 (2012) R. Muñiz-Mendoza et al. 2316 were mestizos. The polymorphisms were detected by PCR-RFLP. Association was estimated by calculating the odds ratio (OR). We found that the MLH1 and XRCC1 polymorphisms were in HardyWeinberg equilibrium. The MLH1 655A>G polymorphism in the 655G allele was associated with a 2-fold increase risk for CRC (OR = 2.04 and 95% confidence interval (95%CI) = 1.12-3.69; P < 0.01), while the MLH1 -93G>A polymorphism allele was associated with a protective effect (OR = 0.60, 95%CI = 0.40-0.89; P = 0.01 in the -93A allele and OR = 0.32, 95%CI = 0.13-0.79; P = 0.01 in the AA genotype). The XRCC1 Arg194Trp and Arg399Gln polymorphisms did not show any significant associations. In conclusion, we found that MLH1 -93G>A and 655A>G polymorphisms are associated with CRC in Mexican patients.

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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: 97%

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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The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis

Cited by 13 publications

References 53 publications

Incidence of −93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer

Incidence of −93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer

MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer

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

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