Abstract 2755: Association of established risk variants for obesity and type-2 diabetes with dietary intake in the Multiethnic Cohort Study

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Excess body weight is thought to account for 25 to 30% of common cancers. As the prevalence of obesity increases worldwide, the number of obesity-related cancers is expected to rise. Recent genome-wide association studies (GWAS) have identified common genetic variants associated with obesity and related metabolic conditions, such as type-2 diabetes. However, the mechanisms underlying these associations are unclear. Given that diet plays a critical role in energy balance and glucose metabolism, it is possible that some of these variants affect metabolic disease risk through an effect on food choices. As part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative, we investigated the associations of 31 risk variants identified in published GWAS of obesity and type-2 diabetes with 50 dietary phenotypes (dietary patterns, macronutrients, food groups, and candidate foods) as measured by a quantitative food frequency questionnaire in the Multiethnic Cohort Study. Participants of five race/ethnic groups (African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites) were genotyped for 12 obesity (n=13,181) or 19 type-2 diabetes (n=25,273) risk variants. Linear or logistic regression was employed to test for associations, while adjusting for age, sex and ethnicity. Using an additive risk model for genotypes, we found 37 associations with dietary phenotypes (p-value<0.01) for 17 of the 31 SNPs. Rs8050136, a variant located within the FTO gene which is highly expressed in the hypothalamus and is associated with obesity and type-2 diabetes, had the greatest number of associations (n=9), mostly with macronutrients. Among participants who self-reported as non-diabetic at baseline, for a per-allele change, there was a 0.23±0.076 increase in % calories from fat (p=0.002), mainly from monounsaturated fats, and a 0.29±0.095 decrease in % calories from carbohydrates (p=0.002). These associations remained even after additional adjustments for calories and physical activity. We also found that carriers of the risk allele had an increase in % calories from protein (p=0.013) and were less likely to add salt to foods (p=0.007). The directions of these associations were consistent across sexes and racial/ethnic groups. Consistent with our results, several small studies (4 in children and 3 in adults) reported higher energy intake, increased energy intake from fat, and/or diminished satiety among individuals with the risk allele. Replication studies are ongoing in PAGE. Methods to adjust for multiple comparisons among correlated phenotypes are being applied. In conclusion, these data suggest that the association of rs8050136 with obesity may at least partially be the result of a dietary preference for fat. If reproduced, these data may have relevance to the prevention of obesity and obesity-related cancers in risk allele carriers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2755. doi:10.1158/1538-7445.AM2011-2755