Genetic variation in the nucleotide excision repair pathway and colorectal cancer risk

Sonja I. Berndt, Elizabeth A Platz, Daniele Daniele Fallin, Lucy W. Thuita, Sandra C. Hoffman, Kathy J. Helzlsouer

Research output: Contribution to journalArticle

Abstract

Nucleotide excision repair (NER) enzymes are critical for the removal of bulky DNA adducts caused by environmental carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons, which are found in two putative risk factors for colorectal cancer, tobacco smoke and meat cooked at high temperature. To examine the association between common genetic variants in NER genes and the risk of colorectal cancer, we conducted a case-cohort study within the CLUE II cohort. Twenty-two single nucleotide polymorphisms in 11 NER genes were genotyped in 250 colorectal cancer cases and a subcohort of 2,224 participants. Incidence rate ratios (RR) and 95% confidence intervals (95% CI) were estimated using a modified Cox regression model and robust variance estimate. The ERCC6 1213G variant, which is thought to reduce NER capacity, was associated with an increased risk of colorectal cancer compared with the homozygous wild type (RR, 1.36; 95% CI, 1.00-1.86 and RR, 2.64; 95% CI, 1.53-4.58 for the RG and GG genotypes respectively with Ptrend = 0.0006). Having at least one XPC 492H allele was also associated with an increased risk of colorectal cancer (RR, 1.75; 95% CI, 1.20-2.57). When the combined effects of ERCC6 R1213G and XPC R492H were examined, the risk of colorectal cancer significantly increased with increasing number of variant alleles (Ptrend = 0.00003). Our study suggests that genetic polymorphisms in the NER genes, ERCC6 and XPC, may be associated with an increased risk of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)2263-2269
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number11
DOIs
StatePublished - Nov 2006

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DNA Repair
Colorectal Neoplasms
Confidence Intervals
Alleles
Environmental Carcinogens
Genes
DNA Adducts
Polycyclic Aromatic Hydrocarbons
Genetic Polymorphisms
Proportional Hazards Models
Smoke
Meat
Tobacco
Amines
Single Nucleotide Polymorphism
Cohort Studies
Genotype
Temperature
Incidence
Enzymes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Genetic variation in the nucleotide excision repair pathway and colorectal cancer risk. / Berndt, Sonja I.; Platz, Elizabeth A; Fallin, Daniele Daniele; Thuita, Lucy W.; Hoffman, Sandra C.; Helzlsouer, Kathy J.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 15, No. 11, 11.2006, p. 2263-2269.

Research output: Contribution to journalArticle

Berndt, Sonja I. ; Platz, Elizabeth A ; Fallin, Daniele Daniele ; Thuita, Lucy W. ; Hoffman, Sandra C. ; Helzlsouer, Kathy J. / Genetic variation in the nucleotide excision repair pathway and colorectal cancer risk. In: Cancer Epidemiology Biomarkers and Prevention. 2006 ; Vol. 15, No. 11. pp. 2263-2269.
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