Back to Search
Start Over
Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review.
- Source :
-
American journal of epidemiology [Am J Epidemiol] 2005 Nov 15; Vol. 162 (10), pp. 925-42. Date of Electronic Publication: 2005 Oct 12. - Publication Year :
- 2005
-
Abstract
- Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to cancer risk. However, epidemiologic findings have been inconsistent. The authors conducted meta-analyses of associations between genes in the base excision repair pathway and cancer risk, focusing on three key genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1), and x-ray repair cross-complementing group 1 (XRCC1). They found increased lung cancer risk among subjects carrying the OGG1 Cys/Cys genotype (odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.01, 1.53), using 3,253 cases and 3,371 controls from seven studies; this is consistent with experimental evidence that this isoform exhibits decreased activity. They found a protective effect of the XRCC1 194Trp allele for tobacco-related cancers (OR = 0.86, 95% CI: 0.77, 0.95), using 4,895 cases and 5,977 controls from 16 studies; this is compatible with evidence of lower mutagen sensitivity for this allele. The XRCC1 399Gln/399Gln genotype was associated with increased risk of tobacco-related cancers among light smokers (OR = 1.38, 95% CI: 0.99, 1.94) but decreased risk among heavy smokers (OR = 0.71, 95% CI: 0.51, 0.99), suggesting effect modification by tobacco smoking. There was no association between cancer risk and the APE1/APEX1 Asp148Glu and XRCC1 Arg280His polymorphisms. Recommendations for future studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure.
- Subjects :
- Confidence Intervals
DNA, Neoplasm genetics
Gene Frequency genetics
Global Health
Humans
Lung Neoplasms epidemiology
Lung Neoplasms genetics
Odds Ratio
Prevalence
Racial Groups genetics
Racial Groups statistics & numerical data
Smoking epidemiology
Smoking genetics
X-ray Repair Cross Complementing Protein 1
DNA Glycosylases genetics
DNA Repair genetics
DNA-(Apurinic or Apyrimidinic Site) Lyase genetics
DNA-Binding Proteins genetics
Neoplasms epidemiology
Neoplasms genetics
Polymorphism, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9262
- Volume :
- 162
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- American journal of epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 16221808
- Full Text :
- https://doi.org/10.1093/aje/kwi318