5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer
Autor: | Robert A. Wolff, Donghui Li, Manal M. Hassan, Renato Lenzi, Ta Hsu Chou, James L. Abbruzzese, Li Jiao, Douglas B. Evans, Maha Ahmed, Melissa L. Bondy, Peter W.T. Pisters, Yanan Li |
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Rok vydání: | 2005 |
Předmět: |
Adult
Male medicine.medical_specialty Pancreatic disease Alcohol Drinking Genotype Epidemiology Adenocarcinoma Gastroenterology Folic Acid Risk Factors Pancreatic cancer Internal medicine medicine Odds Ratio Humans Methylenetetrahydrofolate Reductase (NADPH2) Aged Polymorphism Genetic biology business.industry Smoking Case-control study Odds ratio Middle Aged medicine.disease Confidence interval Pancreatic Neoplasms Endocrinology Oncology Methylenetetrahydrofolate reductase Case-Control Studies biology.protein Female business |
Zdroj: | Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 14(6) |
ISSN: | 1055-9965 |
Popis: | To test the hypothesis that 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms modify the risk of pancreatic cancer, we conducted a hospital-based, case-control study involving 347 patients with newly diagnosed pancreatic adenocarcinoma and 348 healthy controls, frequency matched by age, sex, and race. MTHFR polymorphisms were determined using the PCR-RFLP method. Association of these polymorphisms with the risk of pancreatic cancer was estimated by unconditional logistic regression analysis. We found that the C667T (but not the A1298C) polymorphism had a significant main effect on the risk of pancreatic cancer. The frequencies of the MTHFR 667CC, 667CT, and 667TT genotypes were 49.5%, 38.6%, and 11.9%, respectively, among cases compared with 48.5%, 45.0%, and 6.5%, respectively, among controls. Individuals with the 667TT genotype displayed a 2-fold increased risk for pancreatic cancer compared with those with the CC/CT genotypes [adjusted odds ratio (OR), 2.14; 95% confidence interval (95% CI), 1.14-4.01]. Multivariate analyses found that the effect of the 677TT genotype on the risk of pancreatic cancer was present among ever smokers (OR, 5.53; 95% CI, 2.0-15.3) and ever alcohol drinkers (OR, 3.16; 95% CI, 1.30-7.69) but not in never smokers (OR, 0.82; 95% CI, 0.33-2.06) and never drinkers (OR, 1.42; 95% CI, 0.56-3.62). Furthermore, a positive interaction between the MTHFR TT genotype and heavy smoking or heavy alcohol consumption was detected. The OR (95% CI) of pancreatic cancer was 6.83 (1.91-24.38) for heavy smokers among the TT carriers compared with never smokers with the CC/CT genotypes and 4.23 (0.88-20.3) for heavy drinkers with the TT genotype compared with nondrinkers with the CC/CT genotypes. These observations support a role for folate metabolism in pancreatic cancer, especially among smokers and heavy drinkers. |
Databáze: | OpenAIRE |
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