A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a Danish prospective case-cohort study.
BACKGROUND
Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of RAI IVS1 A4364GA, ERCC1 Asn118AsnT and ASE-1 G-21AG. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer.


METHODS
Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter.


RESULTS
No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed.


CONCLUSIONS
Our results suggest that the ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption, respectively, in relation to the risk of colorectal cancer.
Hansen
Rikke D
RD
National Research Centre for the Working Environment, Lersø Parkalle 105, 2100 Copenhagen, Denmark. RikkeHan@cancer.dk
Sørensen
Mette
M
Tjønneland
Anne
A
Overvad
Kim
K
Wallin
Håkan
H
Raaschou-Nielsen
Ole
O
Vogel
Ulla
U
D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012318:RNA Polymerase I; D012097:Repressor Proteins; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*
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