Circulating biomarkers of one-carbon metabolism in relation to renal cell carcinoma incidence and survival

Mattias Johansson*, Anouar Fanidi, David C. Muller, Julie K. Bassett, Øivind Midttun, Stein Emil Vollset, Ruth C. Travis, Domenico Palli, Amalia Mattiello, Sabina Sieri, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Börje Ljungberg, Göran Hallmans, Elisabete Weiderpass, Guri Skeie, Carlos A. González, Miren Dorronsoro, Petra H. PeetersH. B. Bueno-De-Mesquita, Martine M. Ros, Marie Christine Boutron Ruault, Guy Fagherazzi, Françoise Clavel, María José Sánchez, Aurelio Barricarte Gurrea, Carmen Navarro, J. Ramon Quiros, Kim Overvad, Anne Tjønneland, Krassimira Aleksandrova, Paolo Vineis, Marc J. Gunter, Rudolf Kaaks, Graham Giles, Caroline Relton, Elio Riboli, Heiner Boeing, Per Magne Ueland, Gianluca Severi, Paul Brennan

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)


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 385747 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.

Original languageEnglish
Article numberdju327
JournalJournal of the National Cancer Institute
Issue number12
Publication statusPublished - 1 Dec 2014
Externally publishedYes


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