Methylenetetrahydrofolate reductase polymorphism and risk of colorectal adenomas

Marugame, Tomomi; Tsuji, Emiko; Inoue, Hisako; Shinomiya, Sachiko; Kiyohara, Chikako; Onuma, Kazuya; Hamada, Hatsuyuki; Koga, Hironori; Handa, Koichi; Hayabuchi, Hitomi; Kono, Suminori

doi:10.1016/s0304-3835(99)00412-7

Cited by 46 publications

(34 citation statements)

References 25 publications

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“…Although we did not have the data on serum folate or homocysteine levels, our finding of increased risk of gastric cancer associated with the variant 677CT and 667TT genotype is consistent with a deficient dietary folate intake in at-risk Chinese populations. 6,14 There have been conflicting reports 23,26,32,33 on the association between the MTHFR C677T polymorphism and risk of colorectal cancer. Ma et al 26 and Chen et al 23 reported significantly lower risk of colon cancer in men with the MTHFR 677TT genotype than in men with the MTHFR 677CC or 677CT genotypes in the Physician's Health Study and Health Professional Study.…”

Section: Resultsmentioning

confidence: 99%

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: A case-control study

Shen¹,

Xu²,

Zheng³

et al. 2001

Int. J. Cancer

116

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Low dietary folate intake has been associated with increased risk of gastric cancer. The 5,10-methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has 2 variants, C677T and A1298C, that result in decreased MTHFR activity and lower plasma folate levels. Therefore, we hypothesized that these 2 variants play a role in gastric carcinogenesis. We tested this hypothesis in a Chinese population-based case-control study of 187 histopathologically confirmed gastric cancer cases and 166 healthy controls frequency-matched by age (+/-5 years), gender and residential area. The 677TT genotype was associated with increased risk for gastric cancer [adjusted odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.00-3.48] compared to the 677CC genotype. This association was more pronounced for gastric cardia cancer (adjusted OR = 2.47, 95% CI = 1.14-5.32). However, no evidence was found for risk associated with the MTHFR A1298C polymorphism. Our findings support the hypothesis that MTHFR C677T variants contribute to gastric carcinogenesis, particularly in gastric cardia. Larger studies incorporating dietary folate intake and serum levels are needed to confirm our findings.

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Section: Resultsmentioning

confidence: 99%

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: A case-control study

Shen¹,

Xu²,

Zheng³

et al. 2001

Int. J. Cancer

116

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“…Cigarette smoking was related to an increased risk of colorectal adenomas, 20) and was also a strong correlate of IGF-I and IGFBP-3 in the study population. 19) Neither alcohol use nor physical activity seemed to be an important confounding factor; alcohol use was a correlate of plasma IGF-I and IGFBP-3, 19) but was unrelated to colorectal adenomas, 21) and physical activity was virtually unrelated to IGF-I and IGFBP-3.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like Growth Factor (IGF)‐I, IGF‐binding Protein‐3 and Colorectal Adenomas in Japanese Men

Teramukai

Rohan

Lee

et al. 2002

Japanese Journal of Cancer Research

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“…These two studies were discarded. Among 11 eligible articles (Chen et al 1998;Ulrich et al 1999;Levine et al 2000;Marugame et al 2000;Giovannucci et al 2003;Pufulete et al 2003;Boyapati et al 2004;Goode et al 2004;van den Donk et al 2005;Hirose et al 2005;Mitrou et al 2006), 27% (3/11) stated that the age and sex status were matched between the case and control populations. PCR-RFLP was used to validate the genotype in all of the studies.…”

Section: Selection Of Studiesmentioning

confidence: 99%

Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis

et al. 2006

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Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls) showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval (CI) 0.89-0.98, P=0.22 (for heterogeneity)] for a worldwide population. Metaanalyses of other genetic contrasts suggested that the 677T allele is more likely to affect CRC in a recessive genetic model worldwide (P<0.0001, OR=0.86; 95% CI 0.76-0.96, P=0.06) and in Asians (P=0.0005, OR=0.75; 95% CI 0.64-0.88, P=0.71). Similarly, we found a significantly decreased risk of CRC for 1298C polymorphism (4,764 CRC patients and 6,592 controls) for a recessive genetic model worldwide (P=0.005, OR=0.81; 95% CI 0.70-0.94, P=0.40) and in Caucasians (P=0.04, P=0.35). No evidence of association of C677T (4,616 patients and 6,338 controls) and A1298C (1,272 patients and 1,684 controls) with colorectal adenoma were found. The evidence accumulated suggests that MTHFR may represent a low-penetrance susceptible gene for CRC, and that the two polymorphisms might protect against colorectal adenoma developing into cancer. A larger single study is required to further evaluate gene-gene and geneenvironment interactions for MTHFR polymorphisms and the cancer risk in a specific population.

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Methylenetetrahydrofolate reductase polymorphism and risk of colorectal adenomas

Cited by 46 publications

References 25 publications

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: A case-control study

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: A case-control study

Insulin‐like Growth Factor (IGF)‐I, IGF‐binding Protein‐3 and Colorectal Adenomas in Japanese Men

Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis

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