title: Gene-environment interaction involved in cholangiocarcinoma in the Thai population: polymorphisms of DNA repair genes, smoking and use of alcohol.
abstract: OBJECTIVE
  Cholangiocarcinoma (CCA) is the most common malignancy in a Northeast Thai population. Smoking and alcohol drinking are associated with the production of free radical intermediates, which can cause several types of DNA lesions. Reduced repair of these DNA lesions would constitute an important risk factor for cancer development. We therefore examined whether polymorphisms in DNA base-excision repair (BER) genes, XRCC1 G399A and OGG1 C326G, were associated with CCA risk and whether they modified the effect of smoking and alcohol drinking in the Thai population.
  
  
  METHODS
  A nested case-control study within the cohort study was conducted: 219 participants with primary CCA were each matched with two non-cancer controls from the same cohort on sex, age at recruitment and the presence/absence of Opisthorchis viverrini eggs in stools. Smoking and alcohol consumption were assessed on recruitment. Polymorphisms in BER genes were analysed using a PCR with high-resolution melting analysis. The associations were assessed using conditional logistic regression.
  
  
  RESULTS
  Our results suggest that, in the Thai population, polymorphisms in XRCC1 and OGG1 genes, particularly in combination, are associated with increased susceptibility to CCA, and that their role as modifiers of the effect of smoking and alcohol consumption influences the risk of CCA.
  
  
  CONCLUSIONS
  Better ways of reducing habitual smoking and alcohol consumption, targeted towards subgroups which are genetically susceptible, are recommended. CCA is a multifactorial disease, and a comprehensive approach is needed for its effective prevention. This approach would also have the additional advantage of reducing the onset of other cancers.
authors.affiliation: Department of Community Health, Faculty of Public Health, Ubon Ratchathani Rajabhat University, Ubon Ratchathani, Thailand.
authors.forename: Nopparat
authors.initials: N
authors.lastname: Songserm
authors.affiliation: Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supannee
authors.initials: S
authors.lastname: Promthet
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chamsai
authors.initials: C
authors.lastname: Pientong
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Tipaya
authors.initials: T
authors.lastname: Ekalaksananan
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Peechanika
authors.initials: P
authors.lastname: Chopjitt
authors.affiliation: Department of Paediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Cancer Unit, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Surapon
authors.initials: S
authors.lastname: Wiangnon
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology*; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001650:Bile Duct Neoplasms / Q000453:epidemiology / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000453:epidemiology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000453:epidemiology*; D013785:Thailand / Q000453:epidemiology; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human
keywords: EPIDEMIOLOGY; PUBLIC HEALTH