Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/Hannan/33513
Title: Genetic Variation in the Base Excision Repair Pathway, Environmental Risk Factors, and Colorectal Adenoma Risk
Authors: Corral, Roman;Lewinger, Juan Pablo;Joshi, Amit D.;Levine, A. Joan;Vandenberg, David J.;Haile, Robert W.;Stern, Mariana C.
subject: Biology;Genetics;Population Genetics;Genetic Polymorphism;Molecular Cell Biology;Nucleic Acids;DNA;DNA repair;Medicine;Epidemiology;Biomarker Epidemiology;Cancer Epidemiology;Genetic Epidemiology;Molecular Epidemiology;Gastroenterology and Hepatology;Gastrointestinal Cancers;Oncology;Cancers and Neoplasms;Gastrointestinal Tumors;Colon Adenocarcinoma;Public Health;Alcohol
Year: 2013
Publisher: Public Library of Science
Description: Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER). We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation.
URI: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741365/pdf/
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855760
Standard no: Corral, Roman, Juan Pablo Lewinger, Amit D. Joshi, A. Joan Levine, David J. Vandenberg, Robert W. Haile, and Mariana C. Stern. 2013. “Genetic Variation in the Base Excision Repair Pathway, Environmental Risk Factors, and Colorectal Adenoma Risk.” PLoS ONE 8 (8): e71211. doi:10.1371/journal.pone.0071211. http://dx.doi.org/10.1371/journal.pone.0071211.
1932-6203
Appears in Collections:HSPH Scholarly Articles

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