One-carbon metabolism and renal cell carcinoma: A systematic review and meta-analysis


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Joanna Clasen1,Alicia Heath1,David Muller1
1Imperial College London



Renal cell carcinoma (RCC) is the most common type of kidney cancer, and it is predicted to comprise an increasing proportion of the cancer burden in the UK in the coming decades.  Data on the role of diet in RCC risk and prognosis is largely inconclusive; however, components of one-carbon (1C) metabolism, including multiple B vitamins, may be related to RCC outcomes.  1C metabolism is suspected to play a role in both cancer risk and tumour progression because it is required for several key processes including DNA repair and methylation reactions.


We conducted a systematic review and meta-analysis of 1C metabolites (riboflavin, vitamin B6, folate, vitamin B12, methionine, homocysteine, choline, and betaine) and RCC.  Publications from Medline and Embase database searches were assessed for eligibility and risk of bias then included in nutrient-specific meta-analyses to estimate summary relative risks (RRs) and 95% credible intervals (CIs) using Bayesian methods.  Studies analysing all kidney cancers were pooled with the RCC-specific studies in secondary analyses to increase the sample size.


Twelve papers were included in meta-analyses.  The number of studies per exposure was generally low, with folate intake (k = 6) having the most.  No exposure for either intake or biomarkers showed a significant association with RCC risk. When overall kidney cancer was pooled with RCC, folate intake showed a 17% reduction in risk (RR = 0.83, 95% CI 0.70 – 0.998).


While this meta-analysis does not provide strong evidence of an association between 1C metabolism and RCC risk, this was likely influenced by a lack of power, and further study on this topic is warranted.  Most existing research has a narrow focus on isolated components of 1C metabolism.  Future research should emphasise the complexity and adaptability of 1C metabolism.