Dietary patterns, polygenic risk, and kidney cancer incidence: a UK Biobank cohort study

Diet and genetic risk are established risk factors for kidney cancer, but their interaction remains unclear. This study aims to systematically investigate the associations between various dietary patterns and kidney cancer risk, as well as to evaluate the combined effects of diet and genetic risk on kidney cancer risk.

We conducted a prospective cohort study involving 113,594 participants from the UK Biobank who completed at least two 24-hour dietary recalls, and adherence to four dietary patterns (Alternate Mediterranean Index (aMED), Alternative Healthy Eating Index 2010 (AHEI), dietary approaches to stop hypertension (DASH), and dietary inflammatory index (DII)) was assessed. Incident kidney cancer cases were ascertained via records. Genetic risk was quantified using polygenic risk score (PRS). Associations were evaluated using Cox proportional hazards models, adjusting for confounders. Furthermore, mediation analyses were conducted to identify potential mediators.

During a median follow-up of 11.44 years, 425 participants developed kidney cancer. Higher aMED (HR = 0.71, 95% CI: 0.54-0.94) and DASH (HR = 0.67, 95% CI: 0.49-0.90) were associated with reduced risk of kidney cancer, while higher DII was associated with increased risk (HR = 1.36, 95% CI: 1.02-1.79). Moreover, participants with high genetic risk combined with low aMED, AHEI and DASH scores or high DII score presented the highest kidney cancer risk. Additive interaction was observed between genetic risk and AHEI as well as DII. Moreover, a series of biochemical indicators were identified as potential mediators, with the mediation proportions ranging from 0.76% to 8.40%.

Adherence to healthy dietary patterns, such as aMED, AHEI, and DASH is associated with a reduced risk of kidney cancer, whereas a pro-inflammatory diet confers a greater risk, particularly in high-genetic-risk populations. These findings provide strong evidence that promoting these healthy dietary patterns represents a promising public health strategy for the primary prevention of kidney cancer.