Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat

Asgeir Brevik, Amit D. Joshi, Román Corral, N. Charlotte Onland-Moret, Kimberly D. Siegmund, Loïc Le Marchand, John A. Baron, Maria Elena Martinez, Robert W. Haile, Dennis J. Ahnen, Robert S. Sandler, Peter Lance, Mariana C. Stern

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63 Scopus citations

Abstract

Background: A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Methods: Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Results: Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). Conclusions: We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Impact: Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat.

Original languageEnglish (US)
Pages (from-to)3167-3173
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Brevik, A., Joshi, A. D., Corral, R., Onland-Moret, N. C., Siegmund, K. D., Le Marchand, L., Baron, J. A., Martinez, M. E., Haile, R. W., Ahnen, D. J., Sandler, R. S., Lance, P., & Stern, M. C. (2010). Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat. Cancer Epidemiology Biomarkers and Prevention, 19(12), 3167-3173. https://doi.org/10.1158/1055-9965.EPI-10-0606