Carcinogenesis Advance Access originally published online on November 24, 2008
Carcinogenesis 2009 30(3):472-479; doi:10.1093/carcin/bgn260
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Red meat and poultry intake, polymorphisms in the nucleotide excision repair and mismatch repair pathways and colorectal cancer risk
Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, CA 90089, USA
1 Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA
2 Arizona Cancer Center, Mel and Enid Zuckerman Arizona College of Public Health, University of Arizona, Tucson, AZ 85724, USA
3 Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
4 Department of Medicine, Denver Department of Veterans Affairs Medical Center and University of Colorado Denver School of Medicine, 80262
5 Department of Epidemiology
6 Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
* To whom correspondence should be addressed. Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, room 5421A, Los Angeles, CA 90089, USA. Tel: +1 323 865 0811; Fax: +1 323 442 7787;Email: stern_m{at}ccnt.usc.edu
Diets high in red meat have been consistently associated with colorectal cancer (CRC) risk and may result in exposure to carcinogens that cause DNA damage [i.e polycyclic aromatic hydrocarbons, heterocyclic amines (HCAs) and N-nitroso compounds]. Using a family-based study, we investigated whether polymorphisms in the nucleotide excision repair (NER) (ERCC1 3' untranslated region (UTR) G/T, XPD Asp312Asn and Lys751Gln, XPC intron 11 C/A, XPA 5' UTR C/T, XPF Arg415Gln and XPG Asp1104His) and mismatch repair (MLH1 Ile219Val and MSH2 Gly322Asp) pathways modified the association with red meat and poultry intake. We tested for gene–environment interactions using case-only analyses (n = 577) and compared the results using case-unaffected sibling comparisons (n = 307 sibships). Increased risk of CRC was observed for intake of more than or equal to three servings per week of red meat [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.3–2.5)] or high-temperature cooked red meat (OR = 1.6, 95% CI = 1.1–2.2). Intake of red meat heavily brown on the outside or inside increased CRC risk only among subjects who carried the XPD codon 751 Lys/Lys genotype (case-only interaction P = 0.006 and P = 0.001, respectively, for doneness outside or inside) or the XPD codon 312 Asp/Asp genotype (case-only interaction P = 0.090 and P < 0.001, respectively). These interactions were stronger for rectal cancer cases (heterogeneity test P = 0.002 for XPD Asp312Asn and P = 0.03 for XPD Lys751Gln) and remained statistically significant after accounting for multiple testing. Case-unaffected sibling analyses were generally supportive of the case-only results. These findings highlight the possible contribution of diets high in red meat to the formation of lesions that elicit the NER pathway, such as carcinogen-induced bulky adducts.
Abbreviations: CI, confidence interval; Colon-CFR, Colon Cancer Family Registry; CRC, colorectal cancer; HCA, heterocyclic amine; IOR, interaction odds ratio; MMR, mismatch repair; NER, nucleotide excision repair; NOC, N-nitroso compound; OR, odds ratio; PAH, polycyclic aromatic hydrocarbon; SNP, single-nucleotide polymorphism; USC, University of Southern California; UTR, untranslated region
Received September 6, 2008; revised November 5, 2008; accepted November 13, 2008.