Personalized Nutrition—Genes, Diet, and Related Interactive Parameters as Predictors of Cancer in Multiethnic Colorectal Cancer Families

Abstract

To personalize nutrition, the purpose of this study was to examine five key genes in the folate metabolism pathway, and dietary parameters and related interactive parameters as predictors of colorectal cancer (CRC) by measuring the healthy eating index (HEI) in multiethnic families. The five genes included methylenetetrahydrofolate reductase (MTHFR) 677 and 1298, methionine synthase (MTR) 2756, methionine synthase reductase (MTRR 66), and dihydrofolate reductase (DHFR) 19bp, and they were used to compute a total gene mutation score. We included 53 families, 53 CRC patients and 53 paired family friend members of diverse population groups in Southern California. We measured multidimensional data using the ensemble bootstrap forest method to identify variables of importance within domains of genetic, demographic, and dietary parameters to achieve dimension reduction. We then constructed predictive generalized regression (GR) modeling with a supervised machine learning validation procedure with the target variable (cancer status) being specified to validate the results to allow enhanced prediction and reproducibility. The results showed that the CRC group had increased total gene mutation scores compared to the family members (p < 0.05). Using the Akaike’s information criterion and Leave-One-Out cross validation GR methods, the HEI was interactive with thiamine (vitamin B1), which is a new finding for the literature. The natural food sources for thiamine include whole grains, legumes, and some meats and fish which HEI scoring included as part of healthy portions (versus limiting portions on salt, saturated fat and empty calories). Additional predictors included age, as well as gender and the interaction of MTHFR 677 with overweight status (measured by body mass index) in predicting CRC, with the cancer group having more men and overweight cases. The HEI score was significant when split at the median score of 77 into greater or less scores, confirmed through the machine-learning recursive tree method and predictive modeling, although an HEI score of greater than 80 is the US national standard set value for a good diet. The HEI and healthy eating are modifiable factors for healthy living in relation to dietary parameters and cancer prevention, and they can be used for personalized nutrition in the precision-based healthcare era.

Genomics in Personalized Nutrition: Can You “Eat for Your Genes”?

“…The methylenetetrahydrofolate reductase ( MTHFR) gene encodes for the enzyme, methylenetetrahydrofolate reductase, which catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary form of folate in the blood and a required element (along with vitamin B 12 ) in the conversion of homocysteine to methionine [ 91 ]. There are three common SNPs giving rise to MTHFR alleles, with one SNP (rs1801133) well characterized as causing enzyme deficiencies [ 92 ].…”

TCF7L2 polymorphisms, nut consumption, and the risk of metabolic syndrome: a prospective population based study

“…Identifying potential genes that are associated with MetS and investigating the modifying effect of genetics on the association of dietary determinants with the risk of MetS are among novel approaches for preventing and treating MetS. This approach is based on the precisionbased healthcare that enables use of therapeutic diets and dietary recommendations according to patients' genetic background that eventually, will lead to better prevention and treatment of MetS [4].…”

Saponin-Rich Extracts and Their Acid Hydrolysates Differentially Target Colorectal Cancer Metabolism in the Frame of Precision Nutrition

“…The success of the use of bioactive compounds in precision nutrition as co-adjuvants in the treatment of cancer patients requires the knowledge of their molecular targets and mechanism of action, which will identify the specific subgroup of patients where they should be implemented. Moreover, bioactive compounds may be effective not only against the signaling pathways involved in the tumor process but in alleviating other associated risk factors such as obesity, intestinal dysbiosis, and/or chronic inflammation [ 9 , 10 , 11 , 12 , 13 ].…”