TY - JOUR
T1 - Circulating biomarkers of one-carbon metabolism in relation to renal cell carcinoma incidence and survival
AU - Johansson, Mattias
AU - Fanidi, Anouar
AU - Muller, David C.
AU - Bassett, Julie K.
AU - Midttun, Øivind
AU - Vollset, Stein Emil
AU - Travis, Ruth C.
AU - Palli, Domenico
AU - Mattiello, Amalia
AU - Sieri, Sabina
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Trichopoulos, Dimitrios
AU - Ljungberg, Börje
AU - Hallmans, Göran
AU - Weiderpass, Elisabete
AU - Skeie, Guri
AU - González, Carlos A.
AU - Dorronsoro, Miren
AU - Peeters, Petra H.
AU - Bueno-De-Mesquita, H. B.
AU - Ros, Martine M.
AU - Ruault, Marie Christine Boutron
AU - Fagherazzi, Guy
AU - Clavel, Françoise
AU - Sánchez, María José
AU - Gurrea, Aurelio Barricarte
AU - Navarro, Carmen
AU - Quiros, J. Ramon
AU - Overvad, Kim
AU - Tjønneland, Anne
AU - Aleksandrova, Krassimira
AU - Vineis, Paolo
AU - Gunter, Marc J.
AU - Kaaks, Rudolf
AU - Giles, Graham
AU - Relton, Caroline
AU - Riboli, Elio
AU - Boeing, Heiner
AU - Ueland, Per Magne
AU - Severi, Gianluca
AU - Brennan, Paul
N1 - Funding Information:
The World Cancer Research Fund (UK) supported the biochemical analyses for the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The funding organization had no role in design and conduct of the study, collection, management, analysis, or interpretation of the data, preparation, review, or approval of the manuscript. The work undertaken by DCM that was reported in this paper was done during the tenure of an International Agency for Research on Cancer (IARC)–Australia Postdoctoral Fellowship from the International Agency for Research on Cancer, supported by the Cancer Council Australia. Dr. Ueland reports that he is a member of the steering board of the nonprofit Foundation to Promote Research Into Functional Vitamin B12 Deficiency.
Funding Information:
The EPIC study has been supported by the 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 Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Catalan Institute of Oncology, Spain; the 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 Västerbotten, Sweden; NordForsk (Centre of excellence programme HELGA), Norway; French League against Cancer (LNCC), France; National Institute for Health and Medical Research (INSERM), France; Mutuelle Générale de l’Education Nationale (MGEN), France; 3M Co, France; Gustave Roussy Institute (IGR), France; and General Councils of France.
Publisher Copyright:
© The Author 2014.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84922394561&partnerID=8YFLogxK
U2 - 10.1093/jnci/dju327
DO - 10.1093/jnci/dju327
M3 - Article
C2 - 25376861
AN - SCOPUS:84922394561
SN - 0027-8874
VL - 106
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 12
M1 - dju327
ER -