Association of Genetic Variants of <i>O</i>6-Methylguanine-DNA Methyltransferase with Risk of Lung Cancer in Non-Hispanic Whites

Luo, Wei; Liu, Hongji; Zhang, Zhengdong; Spitz, Margaret R.; Wei, Qingyi

doi:10.1158/1055-9965.epi-06-0437

Cited by 27 publications

(32 citation statements)

References 25 publications

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“…Recently, 2 large studies have reported associations between lung cancer and MGMT. 27,28 Interestingly, both papers did not report significant associations with single markers. Hu et al, 27 genotyped 39 markers across the locus and reported significant results with combinations of haplotypes in certain regions of the gene.…”

Section: Discussionmentioning

confidence: 93%

“…This suggests that the effect of MGMT genotype upon lung cancer risk is modulated by exposure to cigarette smoke and may be apparent only in heavy smokers. Unfortunately, Wang et al 28 did not present results stratified by the degree of smoking. Recently, a protective effect of the 178R allele has also been reported in colorectal cancer and endometrial cancer.…”

Section: Discussionmentioning

confidence: 96%

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Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O⁶‐alkylguanine–DNA alkyltransferase

McGown

Thorncroft

O’Donnell

et al. 2007

Intl Journal of Cancer

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The association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O 6 -alkylguanine-DNA alkyltransferase, which are associated with interindividual differences in activity, have been investigated in 3 hospital-based case-control studies. Genotyping was carried out on 617 subjects of whom 255 had lung cancer. In 2 of the 3 series, there was a significant inverse association between the 178R allele and case status (p < 0.05). In a meta-analysis, the odds ratio (95% CI) associated with the 178R allele relative to the 178K allele was 0.64 (0.45-0.92, p 5 0.01) and 0.51 (0.24-1.11, p 5 0.09) in fixed effects and random effects models, respectively. In a pooled analysis, after adjustment for sex, age, pack years and series, the OR (95% CI) for a heterozygote was 0.67 (0.45-1.01) and for a 178R homozygote was 0.10 (0.01-0.94); the trend for a decreased risk with the number of R alleles was significant (p 5 0.008). This trend was particularly pronounced in heavy smokers (trend test p 5 0.003), but not significant in light smokers (p 5 0.73). There was no evidence of an association between rs12268840 and lung cancer risk. These results suggest that the R allele may protect against lung cancer, specifically in heavy smokers, an effect that may result from this polymorphism affecting the function of the MGMT protein and/or levels in MGMT activity. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O⁶‐alkylguanine–DNA alkyltransferase

McGown

Thorncroft

O’Donnell

et al. 2007

Intl Journal of Cancer

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“…Our data presented here support the notion that a single polymorphism may only contribute to a modest effect, if any, but the use of combined variant genotypes are more likely to identify an association. Therefore, it appears that it is more efficient and effective to include as many functional SNPs in one gene as possible in such association studies [34]. Such an approach should be of special value for evaluating the roles of those genes with low penetration in one's genetic susceptibility to cancer.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of cytosolic serine hydroxymethyltransferase and risk of lung cancer: A case–control analysis

Luo

Shi

et al. 2007

Lung Cancer

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SummaryThe suboptimal DNA repair capacity is a risk factor for cancer that may be modulated by dietary nutrient intake, and the serine hydroxymethyltransferase (SHMT) participates in folate metabolism and synthesis of purine and pyrimidine needed for DNA repair. Therefore, we tested our hypothesis that genetic variants of the cytosolic SHMT (SHMT1) gene are associated with lung cancer risk. In a hospital-based case-control study of 1032 non-Hispanic white lung cancer patients and 1145 matched cancer-free controls, we genotyped five common SHMT1 polymorphisms either in the promoter, exons, or 3′-untranslated regions. Although the genotype and allele frequency distribution of each SNP did not differ between cases and controls statistically significantly in the single-locus analysis, the rs638416 polymorphism in the promoter alone and the combined putative risk variant genotypes containing rs643333C, rs638416G, rs1979277T, rs3738G, and rs1979276C were associated with altered risk. Those carrying the combined 3+ risk variant genotypes had an increased risk of lung cancer (adjusted OR = 1.65, 95% CI = 1.05-2.57, compared with those having 0-1 risk genotypes; and OR = 1.21, 95% CI = 1.01-1.45, compared with those having 0-2 risk genotypes). The risk was more pronounced among older individuals (>61 years) or those having a low total folate intake or a high methionine intake. No evidence of interactions between the putative SHMT risk variant genotypes and the selected variables was found. These results suggest that SHMT1 variants may play a role in the etiology of lung cancer, and our findings need to be verified in larger prospective studies.

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“…We and others have previously reported on the functional effects of several SNPs in the MGMT P/E region [14,21]. While only a few investigators have assessed the effect of some of these SNPs on cancer risk, putative associations with MGMT promoter methylation as well as chemotherapeutic responses, these studies have yielded conflicting results [17][18][19][20][21][24][25][26][27][28][29][30][31][32][33]. This controversy is not surprising because SNPs are not arrayed independently in the genome, but rather occur as combinations forming well-defined haplotypes [34].…”

Section: Introductionmentioning

confidence: 99%

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

Cross

Speidel

et al. 2016

Cell Oncol.

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Association of Genetic Variants of O6-Methylguanine-DNA Methyltransferase with Risk of Lung Cancer in Non-Hispanic Whites

Cited by 27 publications

References 25 publications

Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O⁶‐alkylguanine–DNA alkyltransferase

Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O⁶‐alkylguanine–DNA alkyltransferase

Polymorphisms of cytosolic serine hydroxymethyltransferase and risk of lung cancer: A case–control analysis

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

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Association of Genetic Variants of O6-Methylguanine-DNA Methyltransferase with Risk of Lung Cancer in Non-Hispanic Whites

Cited by 27 publications

References 25 publications

Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6‐alkylguanine–DNA alkyltransferase

Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6‐alkylguanine–DNA alkyltransferase

Polymorphisms of cytosolic serine hydroxymethyltransferase and risk of lung cancer: A case–control analysis

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

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Product

Resources

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Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O⁶‐alkylguanine–DNA alkyltransferase

Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O⁶‐alkylguanine–DNA alkyltransferase