Fruit and vegetable intake has been associated with reduced risk of renal cell cancer, as well as squamous cell carcinoma of the head and neck
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This project was a follow-up of a previous WCRF-funded project that focused on B vitamins and lung cancer that strongly implicated important protective effects on lung cancer for both vitamin B6 and methionine independently of smoking status. B vitamins are essential for DNA synthesis and methylation, and deficiencies may increase the probability of DNA damage and subsequent gene mutations, and may influence gene expression via aberrant methylation patterns.
Major dietary sources of B vitamins are varied and include fruits and green leafy vegetables (folate), fortified cereals and whole grains (vitamin B6), as well as meat and dairy products (vitamin B12). In parallel with lung cancer, fruits and vegetable intake have been associated with reduced risk of renal cell carcinoma (RCC) in a pooled analysis of 13 prospective cohorts, as well as other cancers such as squamous cell carcinoma of the head and neck (HNC).
The project aimed to evaluate the extent to which B and D vitamins may be related to the incidence and survival of RCC, as well as HNC.
This project was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Initially we identified incident RCC (n=557) and HNC (n=350) cases, along with one individually matched control per case.
To replicate and validate initial findings from EPIC, the project also included an analysis of vitamin B6 and D within i) the Melbourne Collaborative Cohort Study (MCCS) in relation to RCC risk, and ii) a large series of newly diagnosed RCC cases recruited in eastern Europe to evaluate the association with disease specific survival when biomarkers were measure at diagnosis.
Statistical methods included both standard conditional and unconditional logistic regression when evaluating relations between biomarkers and risk, as well as Cox-regression and flexible parametric survival models for survival analyses among cancer cases.
Renal Cell Carcinoma
B vitamins: within EPIC, participants with higher plasma concentrations of vitamin B6 had lower risk of RCC (OR 4 vs. 1: 0.43, 95% CI 0.29-0.64, p-trend <.001) after adjusting for potential confounders. In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR 4 vs. 1) of vitamin B6 was 0.57 (95% CI 0.37-0.87, p-trend <.001).
Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR 4 vs. 1 0.47, 95% CI 0.23-0.99, p-trend 0.07), and all-cause mortality (HR 4 vs. 1: 0.56, 95% CI 0.27-1.17, p-trend 0.02).
Vitamin D: a doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season and age at blood draw, sex, and country of recruitment (OR: 0.72, 95% CI [0.60, 0.86], p=0.0004). This was attenuated after additional adjustment for smoking status at baseline, circulating cotinine, alcohol intake, and body mass index (OR 0.82, 95% CI [0.68, 0.99], p=0.038).
Head and Neck Cancer
B vitamins: participants with higher levels of homocysteine had elevated risk of HNC (OR 4 vs. 1: 2.13, 95% CI [1.13-4.00], p-trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (OR Q4 vs. Q1 0.63, 95% CI 0.35-1.16, p-trend 0.02).
Vitamin D: a doubling in 25(OH)D3 concentration was associated with 31% lower risk of head and neck cancer (OR 0.69, 95% CI 0.56-0.87, p-trend 9×10-4) after controlling for risk factors, including tobacco smoking, education and alcohol consumption.
In addition, cases with low 25(OH)D3 concentrations before diagnosis had poorer survival rates than those with higher levels, the hazard ratio for all-cause mortality in HNC cases when comparing 25 versus 50nmol/L of 25(OH)D3 being 1.72 (95% CI 1.11-2.51).
The most important conclusion is that lower concentrations of vitamin B6 are associated with higher risk of developing kidney cancer, and also poorer prognosis among kidney cancer patients. Further research is needed to evaluate if vitamin B6 exerts a causal influence on RCC aetiology, or if other metabolic factors are involved.
We aimed to evaluate if differences in blood concentrations of B-vitamins, as well as vitamin D, are related to risk and survival of renal cell carcinoma (RCC) and head and neck cancer (HNC).
RCC accounts for approximately 3% of cancers in adults in Europe (63,000 new cases out of approximately 2 million), and is of particular significance within areas of central Europe. For example, in the Czech Republic the national incidence exceeds that of any other country worldwide, being around 23/100,000 cases per year among men, and 13/100,000 among women. Established risk-increasing factors of RCC include tobacco smoking, obesity, and hypertension.
It has also been suggested that diabetes mellitus (type 2 diabetes) might increase RCC risk, whereas lifestyle factors such as high physical activity, alcohol intake, and intake of fruits and vegetables may reduce risk. These factors suggest a possible metabolic component, and led us to investigate whether B vitamins and other biomarkers associated with one-carbon metabolism are associated with risk of RCC.
We also investigated these biomarkers in relation to HNC, and additionally evaluated both RCC and HNC in terms of circulating vitamin D.
Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we identified 557 people who were later (several years) diagnosed with RCC, and 350 who were later diagnosed with HNC. We measured all biomarkers for each case and for a set of healthy controls in order to evaluate whether any of the biomarkers are associated with RCC or HNC risk.
We also evaluated whether vitamin B6 or vitamin D was associated with RCC prognosis among 630 RCC cases from Eastern Europe, comparing the concentrations of RCC patients who died versus those who did not.
Lower concentrations of vitamin B6 were associated with higher risk of RCC, and poorer prognosis among RCC patients. HNC risk was higher among those with high concentrations of homocysteine and low concentrations of folate. Circulating concentrations of vitamin D were also inversely associated with risk of both kidney and head and neck cancer.
