MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma

Abstract

Chronic pancreatitis and pancreatic adenocarcinoma are extensively studied as common and potentially lethal disorders. However, their causes and genetic background in most cases remain unclear. The C677T polymorphism in 5',10'-methylenetetrahydrofolate reductase (MTHFR) gene may modulate the risk of pancreatic disorders. In this study, we tested whether MTHFR C677T polymorphism is associated with chronic pancreatitis and pancreatic adenocarcinoma in the Serbian population. DNA was extracted from blood samples of 51 chronic pancreatitis patients, 21 pancreatic adenocarcinoma patients, and a control group consisting of 50 healthy smokers. The MTHFR C677T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Although, no statistically significant differences were observed in the distribution of MTHFR genotype or allele frequencies between patients and control groups, the results showed an increased frequency of homozygotes for MTHFR C677T polymorphism in chronic pancreatitis patients (14%) and a decreased frequency in pancreatic adenocarcinoma patients (5%) in comparison to the control group (8%). We speculate that the MTHFR C677T polymorphism could act as a possible risk factor for chronic pancreatitis and a possible protective factor in pancreatic adenocarcinoma. This observation needs further investigation in prospective studies on a larger number of patients, in which the effect of other genetic and environmental factors should also be taken into consideration.

MTHFR C677T Polymorphism and Pancreatic Cancer Risk: a Meta-analysis

“…Thus, 9 individual case-control studies with a total of 1299 pancreatic cancer cases and 2473 controls were included into this meta-analysis. There were four studies from East Asians (Matsubayashi et al, 2005;Wang et al, 2005;Wang et al, 2006;Yang and Qian, 2009) and three studies from Caucasians (Li et al, 2005;Nisevic et al, 2008;Suzuki et al, 2008). The distribution of MTHFR C677T genotypes was all consistent with HWE in the controls of those 9 studies (All P values for HWE were more than 0.05).…”

“…After excluding those which did not meet the selection criteria, 7 publications were finally included into this meta-analysis (Li et al, 2005;Matsubayashi et al, 2005;Wang et al, 2005;Wang et al, 2006;Nisevic et al, 2008;Suzuki et al, 2008;Yang and Qian, 2009). The study by Li D et al reported three individual casecontrol studies from different ethnicity (Li et al, 2005).…”

“…Recent studies have shown that the MTHFR 677 TT genotype is associated with an increased risk of cancer risk, suggesting an important role of folate levels and subsequent impaired chromosomal DNA synthesis and aberrant DNA methylation in carcinogenesis (Dong et al, 2008). Besides, there were also many published studies investigating the association between MTHFR C677T polymorphism and pancreatic cancer risk, but this possible association remains controversial owing to the conflicting results from those studies (Li et al, 2005;Matsubayashi et al, 2005;Wang et al, 2005;Nisevic et al, 2008;Suzuki et al, 2008). In the present meta-analyses, we aimed to assess the effect of MTHFR C677T polymorphism on pancreatic cancer risk by performing a meta-analysis of all available published and unpublished studies.…”

Genetic Risk for Alcoholic Chronic Pancreatitis

“…These cytokines are important in the development of inflammation and establishment of fibrosis; yet, results were variable and a no clear role was found for determining predisposition to the disease [63–65]. Other studies evaluated genes encoding detoxified enzymes such as glutathione S transferase [66–68], UDP glucuronosyltransferase [69], manganese - superoxide dismutase [66], and methylenetetrahydrofolate reductase [70]. These enzymes provide protection against products of oxidative stress, which apparently contribute to the development of pancreatitis [71].…”

“…These enzymes provide protection against products of oxidative stress, which apparently contribute to the development of pancreatitis [71]. While some researchers [66,67] found no association with chronic pancreatic disease, others [68–70] suggest the presence of low levels of detoxification may be a risk factor. The relevance of genetic variations leading to deficiencies of serum antiproteases, such as alpha 1 antitrypsin and alpha 2 macroglobulin, remains speculative [72,73].…”