title: Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study.
abstract: BACKGROUND
  The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas.
  
  
  METHODS
  We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender.
  
  
  RESULTS
  The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06-1.81), which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15-2.39). The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49-1.01) and carcinomas (OR of 0.49, 95% CI 0.21-1.13) among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95-5.04) compared to all non-carriers although the estimate was not statistically significant.
  
  
  CONCLUSIONS
  We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women.
authors.affiliation: Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, N-3710 Skien, Norway. camilla-furu.skjelbred@sthf.no
authors.forename: Camilla F
authors.initials: CF
authors.lastname: Skjelbred
authors.forename: Mona
authors.initials: M
authors.lastname: Saebø
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Inger-Lise
authors.initials: IL
authors.lastname: Hansteen
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Elin H
authors.initials: EH
authors.lastname: Kure
mesh_terms: D000236:Adenoma / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002277:Carcinoma / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002888:Chromosomes, Human, Pair 19; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012318:RNA Polymerase I; D012097:Repressor Proteins; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; C119975:POLR1G protein, human; D012318:RNA Polymerase I; C071447:ERCC1 protein, human; D004720:Endonucleases