The Association of Gastric Cancer Risk with Plasma Folate, Cobalamin, and <i>Methylenetetrahydrofolate Reductase</i> Polymorphisms in the European Prospective Investigation into Cancer and Nutrition

Vollset, Stein Emil; Igland, Jannicke; Jenab, Mazda; Fredriksen, Åse; Meyer, Klaus; Eussen, Simone J.P.M.; Gjessing, Håkon K.; Ueland, Per Magne; Pera, Guillem; Sala, Núria; Agudo, Antonio; Capellà, Gabriel; Giudice, Giuseppe Del; Palli, Domenico; Boeing, Heiner; Weikert, Cornelia; Bueno‐de‐Mesquita, H. Bas; Carneiro, Fátima; Pala, Valeria; Víneis, Paolo; Tumino, Rosario; Panico, Salvatore; Berglund, Göran; Manjer, Jonas; Stenling, Roger; Hallmans, Göran; Martínez, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Navarro, Carmen; Quiŕos, J. Ramón; Allen, Naomi E.; Key, Timothy J.; Bingham, Sheila; Linseisen, Jakob; Kaaks, Rudolf; Overvad, Kim; Tjønneland, Anne; Büchner, Frederike L.; Peeters, Petra H.M.; Numans, Mattijs E.; Clavel‐Chapelon, Françoise; Boutron‐Ruault, Marie‐Christine; Trichopoulou, Antonia; Lund, Eiliv; Slimani, Nadia; Ferrari, Pietro; Riboli, Elio; González, Carlos

doi:10.1158/1055-9965.epi-07-0256

Cited by 63 publications

(70 citation statements)

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“…In a Mexican population, a significant reduction in gastric cancer risk was observed among individuals with high folate intake and who carried the MTHFR 677TT genotype (Galvan-Portillo et al, 2009). Two other studies detected a non-significant protective effect on gastric cancer risk (Zuniga-Noriega et al, 2007;Vollset et al, 2007). Here, we observed that MTHFR 677TT was associated with a reduced risk of gastric cancer, and the MTHFR 677T allele was associated with a marginally decreased risk.…”

Section: Discussionsupporting

confidence: 58%

“…Studies conducted in China (Qin et al, 2008), Iran (Saberi et al, 2012), Korea (Cui et al, 2010), Mexico (ZunigaNoriega et al, 2007;Galvan-Portillo et al, 2009), Norway (Vollset et al, 2007), and Denmark (Zacho et al, 2011) identified a significant association of the MTHFR C677T polymorphism with gastric cancer. Studies in China, Iran, and Denmark indicated a significantly increased risk of gastric cancer, with ORs ranging from 1.4-2.6 (Qin et al, 2008;Zacho et al, 2011;Saberi et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site

Chen¹,

Yuan²,

Duan³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Folic acid and methylenetetrahydrofolate reductase (MTHFR) may both affect the development of human cancer. We conducted a population-based case-control study in a Chinese population to investigate the potential role of folate intake and MTHFR gene polymorphisms in gastric cancer, and their interaction with infection by Helicobacter pylori and tumor location. A total of 767 patients with newly diagnosed gastric cancer and 775 controls were selected for this study. Genotyping of MTHFR C677T and A1298C was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System, and information 9719 MTHFR and folate and gastric cancer risk ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 9718-9726 (2014) on folate intake was collected by questionnaire. Compared with the CC genotype of MTHFR C677T, the TT genotype was significantly associated with a decreased risk of gastric cancer when the analysis was adjusted for other potential risk factors. We found a marginal significantly decreased risk of gastric cancer for individuals carrying the T allele [adjusted odds ratio (OR) = 0.83; 95% confidence interval (CI) = 0.65-1.01]. We detected an inverse relationship between folate intake and risk of gastric cancer, and the adjusted ORs (95%CI) for moderate and high folate intake were 0.97 (0.74-1.25) and 0.64 (0.49-0.87), respectively. Moreover, H. pylori infection, folate intake, and location of the tumor showed a significant interaction with the MTHFR C677T polymorphism. Our study suggests a protective role of MTHFR 677TT and high folate intake against gastric cancer, and the effect of the MTHFR C677T genotype may differ by H. pylori infection, folate consumption, and tumor site.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site

Chen¹,

Yuan²,

Duan³

et al. 2014

Genet. Mol. Res.

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“…Inverse association of cobalamin to gastric cancer occurrence also exists, while MMA (which is elevated under vitamin B12 deiciency) is positively associated with gastric cancer [50]. This result could be due to worsen vitamin B12 status in atrophic gastritis that often precedes gastric cancer.…”

Section: Vitamin B12 In Cancer Developmentmentioning

confidence: 99%

Vitamin B12: Could It Be a Promising Immunotherapy?

Todorova¹,

Ermenlieva²,

Tsankova³

2017

Immunotherapy - Myths, Reality, Ideas, Future

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Vitamin B12 is a water-soluble vitamin and an important micronutrient with critical role in DNA, protein, and lipid synthesis. It is responsible for one-carbon metabolism and cell division of nervous and hematopoietic cells. Among its various functions, the role as immunomodulator in cellular immunity, especially in elevating the number of CD8+ cells and NK cells, atracts scientiic interest. Many alternative anticancer and anti-inlammatory treatments involve the use of B12 together with other vitamins and nutrients, but still the scientiic information is too obscure and insuicient. Controversial data link tumorigenesis with either increased or decreased B12 blood levels in diferent types of cancer. Dietary intake and additional supplement with the vitamin do not protect against cancer risk, but the dominant opinion is to integrate B12 as part of rational and healthy nutrition to ensure proper function of the immune system. This chapter will review in brief the most important facts for vitamin B12 functions and properties. We will try also to present in concise way the human immune system and the exact role of B12 in immune activity with emphasis on the questionable participation of vitamin B12 in the process of carcinogenesis and its signiicance as anticancer immunotherapy.Keywords: vitamin B12, immunonutrition, immunomodulation, immunotherapy, tumorigenesis, cancer, inlammation IntroductionCancer is the inal outcome of uncontrolled overgrowth of normal cells. Cancer cells remain insensitive to antiproliferative signals and apoptosis. As a result, they replicate, proliferate, and invade ininitely and aggressively. Although the genetic events are thought to be the most important in the process of carcinogenesis, other factors can facilitate abnormal cell development. For many years, inlammation and anti-inlammatory response were widely associated with malignancy [1, 2] and recognized as major elements that trigger carcinogenesis.© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Extended inlammation, especially in chronic infections, predisposes to cancer, but still the mechanism(s) involved is (are) not deinitely known. Usually all inlammatory processes are followed rapidly by anti-inlammatory defense response-excessive production of proinlammatory signals (mediators) and reactive oxygen and nitrogen species. The pro-inlammatory mediators (cytokines, chemokines, and eicosanoids) may stimulate proliferation of both untransformed and tumor cells [2]. The reactive oxygen and nitrogen species lead to oxidative stress and damage of macromolecules, especially DNA to increase the risk of genetic mutations and tumorigenesis [3].A continuously increasing number of microelements, vitamins, and mineral salts are reported to modulate the immune response and counter the inlamm...

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“…Several studies have reported that a homozygous variant genotype of the polymorphism of MTHFR C677T was associated with an increased risk of CRC. Certain studies have reported that individuals with the MTHFR 677TT genotype had a decreased risk of CRC (8), whereas other authors observed no association between the MTHFR C677T genotype and genetic susceptibility to CRC (9)(10)(11). Considering the number of studies performed thus far, inconsistent results have been reported on the association of MTHFR C677T gene polymorphisms with genetic susceptibility to CRC.…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase C677T gene polymorphism and colorectal cancer risk: A case-control study

Yin¹,

Ming²,

Zheng³

et al. 2012

Oncology Letters

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Abstract. We designed a case-control study to determine the plasma homocysteine (Hcy) level and evaluate the potential role of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in colorectal cancer (CRC). Total Hcy was quantified using the fluorescence polarization immunoassay (FPIA) on the IMx analyzer. Genomic DNA was analyzed by the real-time polymerase chain reaction (RT-PCR). The plasma levels of Hcy in the CRC group (12.63±3.11 µmol/l) were significantly higher compared with those in the control group (10.87±2.42 µmol/l; P<0.05). The frequency of the MTHFR 677TT genotype in CRC patients was markedly high. The MTHFR 677TT genotype was significantly correlated with an increased risk of CRC (odds ratio, 1.671; 95% confidence interval, 1.094-2.553; P=0.018). This study suggests that the MTHFR C677T polymorphism indicates susceptibility to CRC and is correlated with CRC pathogenesis, suggesting that the homozygous variant MTHFR C677T polymorphism is a candidate risk factor for CRC.

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The Association of Gastric Cancer Risk with Plasma Folate, Cobalamin, and Methylenetetrahydrofolate Reductase Polymorphisms in the European Prospective Investigation into Cancer and Nutrition

Cited by 63 publications

References 58 publications

Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site

Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site

Vitamin B12: Could It Be a Promising Immunotherapy?

Methylenetetrahydrofolate reductase C677T gene polymorphism and colorectal cancer risk: A case-control study

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