Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 106, Issue 12, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/dju327
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Funding
- World Cancer Research Fund (UK)
- International Agency for Research on Cancer
- Cancer Council Australia
- Europe Against Cancer Program of the European Commission (SANCO)
- Deutsche Krebshilfe
- Deutsches Krebsforschungszentrum
- German Federal Ministry of Education and Research
- Danish Cancer Society
- Health Research Fund (FIS) of the Spanish Ministry of Health
- Spanish Regional Government of Andalucia
- Spanish Regional Government of Asturias
- Spanish Regional Government of Basque Country
- Spanish Regional Government of Murcia
- Spanish Regional Government of Navarra
- Catalan Institute of Oncology, Spain
- ISCIII of the Spanish Ministry of Health [RETICC DR06/0020]
- Cancer Research UK
- Medical Research Council, UK
- Greek Ministry of Health
- Stavros Niarchos Foundation
- Hellenic Health Foundation
- Italian Association for Research on Cancer (AIRC)
- Italian National Research Council
- Fondazione-Istituto Banco Napoli, Italy
- Associazione Italiana per la Ricerca sul Cancro-AIRC-Milan
- Compagnia di San Paolo
- Dutch Ministry of Public Health, Welfare and Sports
- World Cancer Research Fund
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Vasterbotten, Sweden
- NordForsk (Centre of excellence programme HELGA), Norway
- French League against Cancer (LNCC), France
- National Institute for Health and Medical Research (INSERM), France
- Mutuelle Generale de l'Education Nationale (MGEN), France
- 3M Co, France
- Gustave Roussy Institute (IGR), France
- General Councils of France
- MRC [MC_UU_12013/2] Funding Source: UKRI
- Cancer Research UK [16491] Funding Source: researchfish
- Medical Research Council [MC_UU_12013/2] Funding Source: researchfish
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Background The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385 747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. Results EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4th and 1st quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P-trend < .001. We found similar results after adjusting for potential confounders (adjusted P-trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P-trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P-trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P-trend = .02). No association was evident for the other measured biomarkers. Conclusion Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts.
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