Carcinogenesis Advance Access published online on November 24, 2008
Carcinogenesis, 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 (ADJ, RC, KDS, RWH, and MCS); Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii (LLM); Department of Medicine, Denver Department of Veterans Affairs Medical Center and University of Colorado Denver School of Medicine (DJA); Department of Epidemiology and Department of Medicine, University of North Carolina, Chapel Hill, NC (RSS); Arizona Cancer Center, Tucson, AZ (MEM, PL)
1 To whom requests for reprints should be addressed, at the University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, room 5421A, Los Angeles, CA 90089. Telephone (323) 865-0811; E-mail: 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 PAHs, HCAs, NOCs). Using a family-based study, we investigated whether polymorphisms in the nucleotide excision (ERCC1 3’UTR G/T, XPD Asp312Asn and Lys751Gln, XPC intron 11 C/A, XPA 5’UTR – C/T, XPF Arg415Gln, XPG Asp1104His) and mismatch (MLH1 Ile219Val, MSH2 Gly322Asp) repair pathways modified the association with red meat and poultry intake. We tested for gene-environment interactions using case-only analyses (N = 577) and compared results using case-unaffected sibling comparisons (N = 307 sibships). Increased risk of CRC was observed for intake of > 3 servings per week of red meat (OR = 1.8; 95% 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.
Key Words: colorectal neoplasms • meat cooking • nucleotide excision repair • mismatch repair
Received September 6, 2008; revised November 5, 2008; accepted November 13, 2008.