title: Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption and colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population.
  
  
  RESULTS
  SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption.
  
  
  CONCLUSIONS
  Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants.
authors.affiliation: Cancer Prevention and Control Program, Catalan Institute of Oncology, Barcelona, Spain ; Colorectal Cancer Group, Bellvitge Biomedical Research Institute and Consorcio de Investigación Biomédica de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Crous-Bou
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Daniel
authors.initials: D
authors.lastname: Cuadras
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
authors.forename: David
authors.initials: D
authors.lastname: Cordero
authors.forename: Hedy
authors.initials: H
authors.lastname: Saltz Rennert
authors.forename: Flavio
authors.initials: F
authors.lastname: Lejbkowicz
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.forename: Steven
authors.initials: S
authors.lastname: Monroe Lipkin
authors.forename: Stephen
authors.initials: S
authors.lastname: Bernard Gruber
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D015179:Colorectal Neoplasms / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde