Study: Genes influence anti-cancer effectiveness of fruits and fiber

A recent study published in the journal eBioMedicine identified genetic variations that may modify the association between fiber, fruit and vegetable intake and risk of colorectal cancer (CRC). Scientists have successfully identified two significant loci that moderate the association between fiber and fruit intake and CRC risk.

CRC is one of the most common cancers in the world, with nearly two million new cases and more than 900,000 deaths in 2020. High intakes of fruits, vegetables, whole grains, and dietary fiber have been reported to reduce the risk of CRC. Although there is strong evidence of an association between CRC risk and consumption of whole grains and dietary fiber, evidence of an association between CRC risk and fruit and vegetable intake remains limited.

Previous genome-wide association studies (GWAS) have been able to identify at least 200 loci associated with CRC risk, explaining up to 35% of heritability. Although gene-environment (G × E) interactions may explain additional heritability, previous studies with small samples and traditional methods have found only a limited number of significant interactions. New statistical approaches, such as conjoint tests and two-step methods that prioritize single nucleotide polymorphisms (SNPs), can potentially improve the accuracy of these analyses.

Up to 45 studies from three CRC genetic consortia including individuals of European descent were included in the analysis. Studies included case controls for cohort studies and cancer-free controls for case-control studies. A total of 69,599, 69,734, and 44,890 participants were analyzed for fruit, vegetable, and fiber intake, respectively. Dietary intake was assessed using food frequency questionnaires and dietary histories, usually expressed as servings per day for fruits and vegetables and grams per day for total fiber.

Data were harmonized and expressed as quartiles by sex and study. In addition, genotyping quality control included checking for missing data, Hardy-Weinberg equilibrium, and sex inconsistency, followed by imputation and filtering for minor allele frequency and precision, resulting in the analysis of 7,250,911 SNPs.

Compared with controls, participants with CRC were older, had a higher body mass index and energy intake, and a higher prevalence of risk factors such as a family history of CRC and type 2 diabetes. They also consumed less fiber, fruits and vegetables compared to the control group. Meta-analyses found an inverse association between intake of fiber (relative risk per quartile increase (OR) = 0.79), fruit (OR = 0.79) and vegetables (OR = 0.82) and risk of CRC.

The 3-DF test identified the rs4730274 locus upstream of the SLC26A3 gene, which shows an association with fiber intake and an interaction with CRC risk. Stratification by genotype showed a stronger inverse association between fiber and CRC for each copy of the T allele. Functional annotation suggested enhancer activity in colon tissue, with an eQTL for the DLD gene.

The rs1620977 locus near the NEGR1 gene showed a significant association with fruit consumption and a moderate interaction with CRC risk. Strong inverse associations were observed with increasing fruit consumption for each copy of the G allele.

The study is the largest G × E study to date, in which researchers identified two interactions between fiber and fruit intake and CRC risk. In particular, rs4730274 near the SLC26A3 gene suggests a significant association between fiber intake, intestinal function, inflammation and CRC. The results require further research to examine the clinical implications and confirm these findings in different populations.