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Cancer Causes Control. 2010 Jul;21(7):1061-9. doi: 10.1007/s10552-010-9534-5. Epub 2010 Apr 10.

A prospective study of one-carbon metabolism biomarkers and risk of renal cell carcinoma.

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  • 1Yale School of Public Health, 60 College Street, New Haven, CT 06520, USA.



Previous studies have found associations between one-carbon metabolism factors and risk of several cancers, but little is known regarding renal cell carcinoma (RCC). We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a prospective study of Finnish male smokers aged 50-69 at baseline.


Prediagnostic folate, vitamin B(6), vitamin B(12), cysteine, riboflavin, and homocysteine concentrations were measured in fasting serum from 224 incident RCC cases and 224 controls (matched on age and date of serum collection). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders.


Serum folate tended to be inversely associated with RCC, compared to the first quartile, the odds ratios (95% CI) for subsequent quartiles were 0.62 (0.35-1.08), 0.52 (0.29-0.93), and 0.67 (0.37-1.20) (P-trend = 0.19). When modeled as a threshold effect, subjects in the lowest serum folate quartile (<or=6.64 nmol/l), which corresponds to deficient folate status, had a significant increased RCC risk (OR = 1.68, 95% CI 1.06-2.65) compared to those with higher serum folate. The other one-carbon metabolism biomarkers were not associated with RCC.


This study in male smokers suggests that deficient folate status may increase risk of RCC, but confirmation is needed in other epidemiologic studies that include women and non-smokers.

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