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

Abstract

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.

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

“…The frequency of the variant genotype is heterogeneous in different regions of the world. Several studies of Chinese subjects have reported that frequencies of MTHFR 677 C/C, C/T, and T/T were around 31.5~35.0%, 47.8~49.5%, and 15.7~19.0%, respectively, in healthy populations [17,18,25,26], which is similar to the frequencies of 34.5% for C/C, 50.9% for C/T, and 14.6% for T/T in the present study's healthy controls. Among all the studies in Chinese populations, the MTHFR 677 T allele frequency (around 40%) is higher than that observed among Caucasian, African, American, Mexican-American, and Pakistani populations [13,27,28].…”

“…Some of these studies reported that MTHFR 677T allele carriers have reduced risks of colorectal [5][6][7][8][9], leukemia [10][11][12], and lung cancers [29]. In contrast, other studies reported elevated risks of esophageal [17], gastric [18], ovarian [30], cervical [14], bladder [13], colorectal [31,32], and lung cancers [33] for MTHFR 677T allele carriers. These conflicting results might be explained by the modifying effects of the MTHFR polymorphisms on the balance between DNA methylation and DNA synthesis.…”

“…Genotypes with the MTHFR 677T allele have been related to protective effects on colon/rectum cancer [5][6][7][8][9], acute lymphocytic leukemia [10][11][12], and increased cancer risk of the bladder [13], cervix [14], breast [15,16], esophagus [17], and stomach [18]. However, only one epidemiological study estimated the relationship between MTHFR polymorphisms and liver cancer among patients with alcoholic cirrhosis and suggested that the MTHFR 677CC genotype increased the risk of developing HCC among patients with high alcohol consumption [19].…”

Risk Factors for Rectal Cancer and Methylenetetrahydrofolate Reductase Polymorphisms in a Population in Northeast Thailand

“…Indeed, numerous epidemiologic studies have examined the relationship between MTHFR polymorphisms and cancer risk but have generated conflicting results. Several studies have shown that the low-activity variant of MTHFR C677T was associated with a decreased risk for colorectal cancer (Ma et al, 1997;Chen et al, 1999), colon cancer (Slattery et al, 1999) and acute lymphocytic leukemia (Skibola et al, 1999), In contrast, the same variant has also been related to an increased risk for various cancers, including endometrial cancer (Esteller et al, 1997), cervical intraepithelial neoplasia (Piyathilake et al, 2000), esophageal squamous cell carcinoma (Song et al, 2001), gastric cancer (Shen et al, 2001), and bladder cancer (Lin et al, 2004).…”

Using high-throughput SNP technologies to study cancer

“…The activity of thiopurine methyltransferase (TPMT), which catalyses the S-methylation of several thiopurine drugs used in chemotherapy including acute lymphoblastic leukemia (ALL), is defined by several coding polymorphisms (Otterness et al, 1997) and can be used to predict early treatment response in ALL (Stanulla et al, 2005). Functional and common polymorphisms within the MTHFR gene have been linked to colorectal cancer (Ulvik et al, 2004;Jiang et al, 2005;Kono and Chen, 2005), breast cancer (Gershoni-Baruch et al, 2000;Chen et al, 2005), gastric cancer (Shen et al, 2001;Graziano et al, 2006), and pancreatic cancer .…”