Vitamin B6, one-carbon metabolism, and risk of renal cell carcinoma

The incidence of kidney cancer has been increasing over the last several decades. The majority of kidney cancer diagnoses are renal cell carcinoma (RCC), however, evidence on the role of nutrition in RCC risk is unclear. The transsulfuration pathway, part of one-carbon metabolism, requires pyridoxal 5’-phosphate (PLP; the biologically active form of vitamin B6) for the catabolism of homocysteine into cysteine. Several downstream physiological processes rely on one-carbon metabolism, including the oxidative stress response, nucleotide synthesis, and methylation reactions. The overall aim of this thesis is to build a deeper understanding of vitamin B6 and its function as a coenzyme, and explore the role of vitamin B6 as part of one-carbon metabolism in RCC aetiology. This thesis includes a systematic review as well as secondary analysis of data from nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results from the systematic review on components of one-carbon metabolism and RCC risk highlighted the sparsity of available data in this area, but pointed to a possible protective role for B vitamins in the folate cycle. A thorough exploration of markers of vitamin B6 status, function, and metabolism found evidence of variation in the associations of these markers with vitamin B6 intake as well as age, body mass index (BMI), alcohol intake, sex and menopause status, and smoking status. Conditional logistic regression models revealed associations with RCC risk for individual transsulfuration metabolites and for pathway-wide profiles of expected metabolite variation. The results of this thesis provide preliminary evidence of a role for one-carbon metabolism, and especially vitamin B6, in RCC development. The findings highlight the complexity of the role of a metabolic system with strict homeostatic regulation in disease aetiology.Open Acces