Biomarkers of oxidative stress and risk of developing colorectal cancer: A cohort-nested case-control study in the European Prospective Investigation into Cancer and Nutrition

Anke M. Leufkens, Fränzel J B Van Duijnhoven, Sjoukje H S Woudt, Peter D. Siersema, Mazda Jenab, Eugene H J M Jansen, Tobias Pischon, Anne Tjønneland, Anja Olsen, Kim Overvad, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Sophie Morois, Domenico Palli, Valeria Pala, Rosario Tumino, Paolo Vineis, Salvatore Panico, Rudolf Kaaks, Annekatrin LukanovaHeiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Dimitrios Trichopoulos, Vardis Dilis, Petra H. Peeters, Guri Skeie, Carlos A. González, Marcial Argüelles, María José Sánchez, Miren Dorronsoro, José María Huerta, Eva Ardanaz, Göran Hallmans, Richard Palmqvist, Kay Tee Khaw, Nick Wareham, Naomi E. Allen, Francesca L. Crowe, Veronika Fedirko, Teresa Norat, Elio Riboli, H. Bas Bueno-De-Mesquita

Research output: Contribution to journalArticle

Abstract

Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRRadj) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRRadj = 1.89, 95% CI: 1.06, 3.36) and distal (IRRadj = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRRadj = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRRadj = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity <0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.

Original languageEnglish
Pages (from-to)653-663
Number of pages11
JournalAmerican Journal of Epidemiology
Volume175
Issue number7
DOIs
Publication statusPublished - Apr 1 2012

Keywords

  • Biological markers
  • Case-control studies
  • Colorectal neoplasms
  • Oxidative stress

ASJC Scopus subject areas

  • Epidemiology

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    Leufkens, A. M., Van Duijnhoven, F. J. B., Woudt, S. H. S., Siersema, P. D., Jenab, M., Jansen, E. H. J. M., Pischon, T., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M. C., Clavel-Chapelon, F., Morois, S., Palli, D., Pala, V., Tumino, R., Vineis, P., Panico, S., Kaaks, R., ... Bueno-De-Mesquita, H. B. (2012). Biomarkers of oxidative stress and risk of developing colorectal cancer: A cohort-nested case-control study in the European Prospective Investigation into Cancer and Nutrition. American Journal of Epidemiology, 175(7), 653-663. https://doi.org/10.1093/aje/kwr418