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DNA repair polymorphisms and risk of colorectal adenomatous or hyperplastic polyps.
Cancer Epidemiol Biomarkers Prev 2005; 14(11 Pt 1):2501-8CE

Abstract

Genetic variability in DNA repair genes may contribute to differences in DNA repair capacity and susceptibility to cancer, especially in the presence of exposures such as smoking. In a Minnesota-based case-control study of cases with only adenomatous polyps (n = 384), only hyperplastic polyps (n = 191), or both types of polyps (n = 119) versus polyp-free controls (n = 601), we investigated the role of polymorphisms in the DNA repair genes O(6)-methylguanine methyltransferase (MGMT; p.L84F and p.I143V), XPD (p.D312N and p.K751Q), and XPG (p.D1104H). MGMT polymorphisms were not associated with polyp risk. Overall, a homozygous variant XPD-combined genotype was associated with an increased risk of adenomatous polyps [odds ratio (OR), 1.57; 95% confidence interval (95% CI), 1.04-2.38] and an XPGHH1104 genotype with a decreased risk of hyperplastic polyps (OR, 0.36; 95% CI, 0.13-0.98). However, age stratification showed that the XPD association was present only in subjects >/=60 years old (OR, 3.77; 95% CI, 1.94-7.35), whereas the XPG association was observed largely in subjects <60 years old (OR, 0.20; 95% CI, 0.05-0.91). Smokers did not have a significantly increased risk of adenomatous polyps in the absence of synchronous hyperplastic polyps, except for subjects with a homozygous variant XPD genotype or a homozygous wild-type XPG genotype (OR, 3.93; 95% CI, 1.68-9.21 and OR, 1.59; 95% CI, 1.01-2.50, respectively). Smoking was associated with a statistically significant 2.5- to 6-fold increased risk of hyperplastic polyps for individuals with most of the DNA repair genotypes. However, no substantial increase was observed among individuals who were homozygous variant for XPG (1104HH; OR, 1.38; 95% CI, 0.25-7.65). Our data suggest that polymorphisms in DNA repair genes may be risk factors for colorectal neoplasia and that they may exacerbate the effects of exposures to carcinogens.

Authors+Show Affiliations

Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M5-A864, Seattle, WA 98109, USA. jbigler@fhcrc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16284370

Citation

Bigler, Jeannette, et al. "DNA Repair Polymorphisms and Risk of Colorectal Adenomatous or Hyperplastic Polyps." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 14, no. 11 Pt 1, 2005, pp. 2501-8.
Bigler J, Ulrich CM, Kawashima T, et al. DNA repair polymorphisms and risk of colorectal adenomatous or hyperplastic polyps. Cancer Epidemiol Biomarkers Prev. 2005;14(11 Pt 1):2501-8.
Bigler, J., Ulrich, C. M., Kawashima, T., Whitton, J., & Potter, J. D. (2005). DNA repair polymorphisms and risk of colorectal adenomatous or hyperplastic polyps. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 14(11 Pt 1), pp. 2501-8.
Bigler J, et al. DNA Repair Polymorphisms and Risk of Colorectal Adenomatous or Hyperplastic Polyps. Cancer Epidemiol Biomarkers Prev. 2005;14(11 Pt 1):2501-8. PubMed PMID: 16284370.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNA repair polymorphisms and risk of colorectal adenomatous or hyperplastic polyps. AU - Bigler,Jeannette, AU - Ulrich,Cornelia M, AU - Kawashima,Toana, AU - Whitton,John, AU - Potter,John D, PY - 2005/11/15/pubmed PY - 2006/1/13/medline PY - 2005/11/15/entrez SP - 2501 EP - 8 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 14 IS - 11 Pt 1 N2 - Genetic variability in DNA repair genes may contribute to differences in DNA repair capacity and susceptibility to cancer, especially in the presence of exposures such as smoking. In a Minnesota-based case-control study of cases with only adenomatous polyps (n = 384), only hyperplastic polyps (n = 191), or both types of polyps (n = 119) versus polyp-free controls (n = 601), we investigated the role of polymorphisms in the DNA repair genes O(6)-methylguanine methyltransferase (MGMT; p.L84F and p.I143V), XPD (p.D312N and p.K751Q), and XPG (p.D1104H). MGMT polymorphisms were not associated with polyp risk. Overall, a homozygous variant XPD-combined genotype was associated with an increased risk of adenomatous polyps [odds ratio (OR), 1.57; 95% confidence interval (95% CI), 1.04-2.38] and an XPGHH1104 genotype with a decreased risk of hyperplastic polyps (OR, 0.36; 95% CI, 0.13-0.98). However, age stratification showed that the XPD association was present only in subjects >/=60 years old (OR, 3.77; 95% CI, 1.94-7.35), whereas the XPG association was observed largely in subjects <60 years old (OR, 0.20; 95% CI, 0.05-0.91). Smokers did not have a significantly increased risk of adenomatous polyps in the absence of synchronous hyperplastic polyps, except for subjects with a homozygous variant XPD genotype or a homozygous wild-type XPG genotype (OR, 3.93; 95% CI, 1.68-9.21 and OR, 1.59; 95% CI, 1.01-2.50, respectively). Smoking was associated with a statistically significant 2.5- to 6-fold increased risk of hyperplastic polyps for individuals with most of the DNA repair genotypes. However, no substantial increase was observed among individuals who were homozygous variant for XPG (1104HH; OR, 1.38; 95% CI, 0.25-7.65). Our data suggest that polymorphisms in DNA repair genes may be risk factors for colorectal neoplasia and that they may exacerbate the effects of exposures to carcinogens. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/16284370/DNA_repair_polymorphisms_and_risk_of_colorectal_adenomatous_or_hyperplastic_polyps_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16284370 DB - PRIME DP - Unbound Medicine ER -