Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population

Department of Public Health, Qingdao University Medical College, Qingdao, China.
BMC Medical Genetics (Impact Factor: 2.08). 02/2011; 12(1):28. DOI: 10.1186/1471-2350-12-28
Source: PubMed


This study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population.
We conducted a large-scale, case-control study involving 3938 patients with newly diagnosed lung cancer and 1700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. Statistical significance was estimated by logistic regression analysis.
The MTHFR C677T frequencies of CC, CT, and TT genotypes were 34.5%, 48.5%, and 17% among lung cancer patients, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677CT and TT genotype showed a weak protection against lung cancer compared with the homozygous CC genotype, although the results did not reach statistical significance. The age- and gender-adjusted odds ratio (OR) of overall lung cancer was 0.90 (95% confidence interval (CI), 0.77-1.04) for MTHFR 677 CT and 0.88 (95% CI, 0.71-1.07) for MTHFR 677TT. However, after stratification analysis by histological type, the MTHFR 677CT genotype showed a significantly decreased risk for squamous cell carcinoma (age- and gender-adjusted OR, 0.78; 95% CI, 0.64-0.96). The combination of 677 TT homozygous with 677 CT heterozygous also appeared to have a protection effect on the risk of squamous cell carcinoma. We observed no significant interaction between the MTHFR C677T polymorphism and age and gender or smoking habit.
This is the first reported study focusing on the association between MTHFR C677T polymorphisms and the risk of lung cancer in a Korean population. The T allele was found to provide a weak protective association with lung squamous cell carcinoma.

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Available from: In-Jae Oh, Jan 07, 2014
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    • "The enrolled studies were stratified for further analysis by ethnicity, histological type, smoking status and gender. The results are listed in Table 3. Twelve studies evaluated the MTHFR C677T polymorphism and lung cancer risk in Asians.12,13,15,16,29,30,32,35,37-40 Among them, nine studies assessed the association in the Chinese population.13,16,29,30,32,35,38-40 "
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    ABSTRACT: Purpose Methylenetetrahydrofolate reductase (MTHFR) has been implicated in lung cancer risk and response to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the results are controversial. We performed meta-analysis to investigate the effect of MTHFR C677T polymorphism on lung cancer risk and response to platinum-based chemotherapy in advanced NSCLC. Materials and Methods The databases of PubMed, Ovid, Wanfang and Chinese Biomedicine were searched for eligible studies. Nineteen studies on MTHFR C677T polymorphism and lung cancer risk and three articles on C677T polymorphism and response to platinum-based chemotherapy in advanced NSCLC, were identified. Results The results indicated that the allelic contrast, homozygous contrast and recessive model of the MTHFR C677T polymorphism were associated significantly with increased lung cancer risk. In the subgroup analysis, the C677T polymorphism was significantly correlated with an increased risk of NSCLC, with the exception of the recessive model. The dominant model and the variant T allele showed a significant association with lung cancer susceptibility of ever smokers. Male TT homozygote carriers had a higher susceptibility, but the allelic contrast and homozygote model had a protective effect in females. No relationship was observed for SCLC in any comparison model. In addition, MTHFR 677TT homozygote carriers had a better response to platinum-based chemotherapy in advanced NSCLC in the recessive model. Conclusion The MTHFR C677T polymorphism might be a genetic marker for lung cancer risk or response to platinum-based chemotherapy in advanced NSCLC. However, our results require further verification.
    Full-text · Article · Nov 2013 · Yonsei medical journal
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    • "It is well known that both SNPs (C677T and A1298C) of MTHFR gene may lead to a decreased activity of the enzyme. Cui et al. (2011) also suggested that MTHFR C677T SNP may contribute to NSCLC development in Chinese women and could influence treatment response for that patients with platinum-based chemotherapy (Cui et al, 2011). Siemianowicz et al (2003)have reported that all SCLC and NSCLC patients had statistically significantly higher percentage of MTHFR 677TT genotype when compared to the non-cancer controls (Siemianowicz et al, 2003; Vaissière et al., 2009). "
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    ABSTRACT: Background: A large variety of familiar and non-familiar lung carcinomas (LC) are caused by long term exposure to chemical carcinogens that are present in tobacco smoke. We aimed to investigate the prevalence of 5 thrombophilic germ-line mutations in patients with lung carcinomas. Materials and methods: A total of 52 LC patients and 212 healthy controls from same population were analyzed for FV Leiden, factor V H1299R (R2), PAI-1, MTHFR C677T, MTHFR A1298C, ACE I/D, and Apo E genes and compared. Results: Overall, heterozygous and/or homozygous point mutations in FV Leiden Apo E2, PAI-1 and MTHFR C677T genes were associated with LC in the current cohort. There was no meaningful association between LC and ACE I/D gene markers. Conclusions: The current results showed that LC is related to combined thrombophilic gene mutations and individuals with homozygosity of 4G in PAI-1 and MTHFR C677T genes and heterozygosity of FV Leiden, Apo E4 genes have a germ-line risk for LC tumorigenesis.
    Full-text · Article · Sep 2013 · Asian Pacific journal of cancer prevention: APJCP
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    • "However, results of several studies examining the role of the MTHFR C677T polymorphism in lung cancer susceptibility have been inconsistent. Arslan et al., (2011) in Turkey, Siemianowicz et al., (2003) in Poland, Hung et al., (2007) in Central Europe, Shen et al., (2005) in China and a recent meta-analysis by Boccia et al., (2009) in Italy based on 10 case-control studies showed that individuals with MTHFR TT genotype had an increased risk of lung cancer versus those with the wild-type homozygous variant, while others studies such as Suzuki et al., (2007) in Japan, Cui et al., (2011) in Korea and another -meta-analysis by Mao et al., (2008) in china based on 8 case-control studies suggested no evidence for a major role of the MTHFR C677T polymorphisms in carcinogenesis of lung cancer, regardless Liu et al., (2009) and Jeng et al., (2003) in Taiwan and Shi et al., (2005) in Houston, TX showed that the MTHFR 677 TT genotype was associated with a decreased risk of lung cancer. Although different sample size and methodologies might be responsible for this discrepancy, the effect-ion that various ethnic groups, environment, diet habit on MTHFR C677T polymorphisms might be also contributed to this inconsistent results. "
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    ABSTRACT: The current study was performed to assess any association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of lung cancer in Henan province. This case-control study involved94 patients with newly histological confirmed lung cancer and 78 healthy controls. Genotyping was achieved with peripheral blood lymphocytes DNA and association of the polymorphism with risk of lung cancer was estimated by unconditional logistic regression analysis. The frequencies of the MTHFR 667TT genotype were 37.2% in cases compared with 23.1% in controls (χ2 = 4.008, P = 0.045). Individuals with the 667CC/CT genotype displayed a significantly reduced risk of lung cancer compared with those with the TT genotypes [adjusted odds ratio (OR), 0.506; 95% confidence interval (95% CI), 0.258 - 0.991]. The C667T polymorphism might have a significant effect on the occurrence of lung cancer in Henan province.
    Preview · Article · Jun 2012 · Asian Pacific journal of cancer prevention: APJCP
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