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, Ptrend < .001. We found
similar results after adjusting for potential confounders (adjusted Ptrend < .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, Ptrend < .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, Ptrend  =  .07) and all-cause mortality (HR4vs1  =  0.56, 95% CI  =  0.27 to 1.17,
Ptrend = .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.