title: Red meat and poultry intake, polymorphisms in the nucleotide excision repair and mismatch repair pathways and colorectal cancer risk.
abstract: 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.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, CA 90089, USA.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Román
authors.initials: R
authors.lastname: Corral
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Martínez
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Peter
authors.initials: P
authors.lastname: Lance
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002417:Cattle; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D053843:DNA Mismatch Repair; D004260:DNA Repair; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D011200:Poultry; D012004:Rectal Neoplasms / Q000209:etiology / Q000235:genetics*; D012306:Risk; D012756:Sheep; D035781:Siblings; D013552:Swine
chemical_list: D002273:Carcinogens