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Effects of the Ser326Cys Polymorphism in the DNA Repair OGG1 Gene on Cancer, Cardiovascular, and All-Cause Mortality in the PREDIMED Study: Modulation by Diet

Published:January 02, 2018DOI:https://doi.org/10.1016/j.jand.2017.09.025

      Abstract

      Background

      Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet.

      Objective

      Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet.

      Design

      Secondary analysis in the PREDIMED (Prevención con Dieta Mediterránea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010.

      Participants/setting

      Study participants (n=7,170) were at high risk for CVD and were aged 55 to 80 years.

      Intervention

      Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline.

      Main outcome measures

      Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years.

      Statistical analyses

      Multivariable-adjusted Cox regression models were fitted.

      Results

      Three hundred eighteen deaths were detected (cancer, n=127; CVD, n=81; and other, n=110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P=0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carriers was 1.69 (95% CI 1.09 to 2.62; P=0.018). This association was greater for CVD mortality (P=0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P=0.867), but a significant age interaction (P=0.048) was observed, as Cys326Cys was associated with cancer mortality in participants <66.5 years (P=0.029). Recessive effects limited our ability to investigate Cys326Cys×diet interactions for cancer mortality. No statistically significant interactions for total or CVD mortality were found for the Mediterranean diet intervention. However, significant protective interactions for CVD mortality were found for vegetable intake (hazard ratio interaction per standard deviation 0.42; 95% CI 0.18 to 0.98; P=0.046).

      Conclusions

      In this population, the Cys326Cys-OGG1 genotype was associated with all-cause mortality, mainly CVD instead of cancer mortality. Additional studies are needed to provide further evidence on its dietary modulation.

      Keywords

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      Biography

      D. Corella is a professor, Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain, and principal investigator, Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.

      Biography

      J. B. Ramírez-Sabio is a research assistant, Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain, and a medical oncologist, Oncology Department, Sagunto Hospital, Sagunto, Spain.

      Biography

      O. Coltell is a senior research fellow, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and an associate professor, Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Universitat Jaume I, Castellón, Spain.

      Biography

      C. Ortega-Azorín is an adjunct professor, Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain, and a research associate, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.

      Biography

      R. Estruch is coordinator and principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a senior consultant, Department of Internal Medicine, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

      Biography

      M. A. Martínez-González is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, a professor and chair, Department of Preventive Medicine and Public Health, University of Navarra—Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain, and an adjunct professor, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

      Biography

      J. Salas-Salvadó is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a professor, Human Nutrition Unit, Biochemistry and Biotechnology Department, Institut d’Investigació Sanitària Pere Virgili, University Rovira i Virgili, Reus, Spain.

      Biography

      J. V. Sorlí is an assistant professor, Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain, and a research fellow, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.

      Biography

      O. Castañer is a research fellow, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a research fellow, Cardiovascular Risk and Nutrition Research Group, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.

      Biography

      F. Arós is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a consultant, Department of Cardiology, Organización Sanitaria Integrada Araba, University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.

      Biography

      F. J. Garcia-Corte is a senior investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a primary care physician, Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Healthcare Centre, Sevilla, Spain.

      Biography

      L. Serra-Majem is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a professor and director, Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.

      Biography

      E. Gómez-Gracia is a professor, Department of Epidemiology, School of Medicine, University of Malaga, Malaga, Spain.

      Biography

      M. Fiol is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a principal investigator, Balearic Islands Health Research Institute, Instituto de Investigación Sanitaria Illes Balears, Hospital Son Espases, Palma, Spain.

      Biography

      X. Pintó is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a principal investigator, Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Barcelona, Spain.

      Biography

      G. T. Saez is a professor, Department of Biochemistry and Molecular Biology-Service of Clinical Analysis, University of Valencia, University Hospital Dr. Peset, Valencia, Spain.

      Biography

      E. Toledo is co-principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and an associate professor, Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain.

      Biography

      J. Basora is a research fellow, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and an associate professor, Institut d’Investigació Sanitària Pere Virgili, University Rovira i Virgili, Reus, Spain.

      Biography

      M. Fitó is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a principal investigator, Cardiovascular Risk and Nutrition Research Group, IMIM, Barcelona, Spain.

      Biography

      M. Cofán is a research fellow, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and a research fellow, Lipid Clinic, Endocrinology and Nutrition Service, IDIBAPS, Hospital Clinic, Barcelona, Spain.

      Biography

      E. Ros is a principal investigator, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain, and an emeritus professor, Lipid Clinic, Endocrinology and Nutrition Service, IDIBAPS, Hospital Clinic, Barcelona, Spain.

      Biography

      J. M. Ordovas is a director, Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, a principal investigator, Instituto Madrileño de Estudios Avanzados en Alimentación, Madrid, Spain, and a senior investigator, Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.