title: Associations between polymorphisms in folate-metabolizing genes and pancreatic cancer risk in Japanese subjects.
abstract: BACKGROUND
  Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects.
  
  
  METHODS
  Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between folate metabolizing gene variants and pancreatic cancer risk.
  
  
  RESULTS
  Overall we did not observe a significant association between these four genotypes and pancreatic cancer risk. For rs1801133, compared with individuals with the CC genotype of MTHFR C677T, the OR for those with the CT genotype and TT genotype was 0.87 (0.62-1.22) and 0.99 (0.65-1.51), respectively. For rs1801131, individuals with the CC genotype had approximately 1.2-fold increased risk compared with those with the AA genotype, but the association was not statistically significant. In analyses stratified by smoking and drinking status, no significant associations were noted for C677T genotypes. No significant interactions were observed with smoking and drinking with respect to pancreatic cancer risk.
  
  
  CONCLUSIONS
  Our data did not support the hypothesis that MTHFR polymorphisms or other polymorphisms in the folate metabolizing pathway are associated with pancreatic cancer risk.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Nakao
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, 060-0061, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, 060-0061, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, 060-8543, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Sapporo Shirakaba-dai Hospital, Sapporo, 062-0052, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Endo
authors.affiliation: Hepatobiliary and Pancreatic Section, Gastroenterological Division, Cancer Institute Hospital, Tokyo, 135-8550, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Matsuyama
authors.affiliation: Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa, 241-8515, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, 113-8677, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Kuruma
authors.affiliation: Tokyo Metropolitan Otsuka Hospital, Tokyo, 170-8476, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Egawa
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, 762-6111, Japan.|Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, 762-6111, Japan.
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.affiliation: Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa, 241-8515, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohkawa
authors.affiliation: Department of Food and Nutrition, Gifu City Women's College, Gifu, 501-2592, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tamakoshi
authors.affiliation: Central Animal Division, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, 104-0045, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Public Health, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishiyama
authors.affiliation: Department of Public Health, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Department of Public Health, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. linys@aichi-med-u.ac.jp.
authors.forename: Yingsong
authors.initials: Y
authors.lastname: Lin
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking
chemical_list: D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human
keywords: Case-control study; Folate; Pancreatic cancer; Polymorphism; Risk