Lack of Influence of MGMT Codon Leu84Phe and Codon Ileu143Val Polymorphisms on Esophageal Cancer Risk in the Kashmir Valley

Shah, Manjool; Shaffi, Sheikh; Lone, Ghulam Nabi; Jan, Syed Mudassar

doi:10.7314/apjcp.2012.13.7.3047

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…We observed conflicting conclusions about the genetic role of MGMT rs12917 polymorphism in its susceptibility to different cancers. For instance, the polymorphism seems to be associated with the risk of esophageal cancer in the Chinese population [ 41 ], but not in the Kashmiri population [ 50 ]. This merits a quantitative synthesis via the meta-analytic approach.…”

Section: Discussionmentioning

confidence: 99%

“…In 2010, Zhong et al [ 12 ] performed the first meta-analysis on this topic, reviewing 28 case–control studies from 26 articles [ 4 , 5 , 20 , 22 , 23 , 26–28 , 31 , 33–35 , 37 , 38 , 42 , 45 , 49 , 51 , 52 , 54 , 55 , 59–63 ]. Another 24 case–control studies [ 16–19 , 21 , 24 , 25 , 29 , 30 , 32 , 36 , 39–41 , 43 , 44 , 46–48 , 50 , 53 , 56–58 ] were included in our study. We excluded three studies not in-line with the HWE principle [ 61–63 ] and one that focussed only on colorectal adenomatous or hyperplastic polyps but not on colorectal cancer [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, when compared with another meta-analysis of Liu et al (2013) [ 13 ], which consisted of 44 case–control studies from 37 articles [ 4 , 5 , 16 , 17 , 19 , 20 , 22 , 23 , 25–27 , 31–33 , 35 , 37 , 38 , 42 , 43 , 45–47 , 49 , 51 , 52 , 54–63 , 65 , 66 ], we excluded four studies that were not in HWE [ 61–63 , 66 ], one that did not analyze colorectal cancer [ 60 ], and one that included other genetic variants [ 65 ]. We also added another 15 new case–control studies [ 18 , 21 , 24 , 28–30 , 34 , 36 , 39–41 , 44 , 48 , 50 , 53 ] for the analysis.…”

Section: Discussionmentioning

confidence: 99%

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The potential role of MGMT rs12917 polymorphism in cancer risk: an updated pooling analysis with 21010 cases and 34018 controls

2018

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In the present study, we aimed at determining the potential role of rs12917 polymorphism of the -6-methylguanine-DNA methyltransferase () gene in the occurrence of cancer. Based on the available data from the online database, we performed an updated meta-analysis. We retrieved 537 articles from our database research and finally selected a total of 54 case-control studies (21010 cases and 34018 controls) for a series of pooling analyses. We observed an enhanced risk in cancer cases compared with controls, using the genetic models T/T compared with C/C (-value of association test <0.001; odds ratio (OR) = 1.29) and T/T compared with C/C+C/T (<0.001; OR = 1.32). We detected similar positive results in the subgroups 'Caucasian', and 'glioma' (all <0.05; OR > 1). However, we detected negative results in our analyses of most of the other subgroups (>0.05). Begg's and Egger's tests indicated that the results were free of potential publication bias, and sensitivity analysis suggested the stability of the pooling results. In summary, the T/T rs12917 is likely to be linked to an enhanced susceptibility to cancer overall, especially glioma, in the Caucasian population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The potential role of MGMT rs12917 polymorphism in cancer risk: an updated pooling analysis with 21010 cases and 34018 controls

2018

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The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis

Wang

Xiong

et al. 2013

Tumor Biol.

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Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and -485C/A) with 98 case-control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu + Leu/Phe) carriers (odds ratio [OR] = 1.32, 95 % confidence interval [CI] = 1.15-1.52, P < 0.0001 for Phe/Phe vs. Phe/Leu + Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and -485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results.

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Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis

Zhou

et al. 2013

Tumor Biol.

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PARP-1 and MGMT play an important role in the DNA repair system and therefore have been implicated in human carcinogenesis. However, the association between the most studied PARP-1 rs1136410: T > C and MGMT rs12917: C > T polymorphism and risk of gastrointestinal (GI) cancers was reported with inconclusive results. Accordingly, a meta-analysis of 23 published case-control studies was conducted to assess the strength of association using crude odds ratios (ORs) with 95% confidence intervals (CIs). Overall, the C allele of PARP-1 rs1136410: T > C polymorphism was significantly associated with increased susceptibility of GI cancers (homozygote comparison: OR = 1.43, 95% CI 1.14-1.81; heterozygote comparison: OR = 1.18, 95% CI 1.07-1.29; dominant model: OR = 1.23, 95% CI 1.12-1.35; recessive model: OR = 1.30, 95% CI 1.04-1.62; allelic comparison: OR = 1.19, 95% CI 1.07-1.32). In the subgroup analysis, still obvious associations were found in the Asian population, gastric cancer, and high-quality studies. For MGMT rs12917: C > T polymorphism, no obvious associations were found for all genetic models overall. However, in the subgroup analysis, we found that the T allele was significantly associated with reduced colorectal cancer risk for heterozygote (OR = 0.83, 95% CI 0.70-0.97) and dominant model (OR = 0.84, 95% CI 0.72-0.98). In conclusion, this meta-analysis suggests that the PARP-1 rs1136410: T > C polymorphism is a susceptibility factor for GI cancers, but the variant allele of MGMT rs12917: C > T polymorphism appears to be a protective factor for colorectal cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.

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Lack of Influence of MGMT Codon Leu84Phe and Codon Ileu143Val Polymorphisms on Esophageal Cancer Risk in the Kashmir Valley

Cited by 5 publications

References 19 publications

The potential role of MGMT rs12917 polymorphism in cancer risk: an updated pooling analysis with 21010 cases and 34018 controls

The potential role of MGMT rs12917 polymorphism in cancer risk: an updated pooling analysis with 21010 cases and 34018 controls

The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis

Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis

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