Background: Greater acculturation to the U.S. dietary habits has been suggested to contribute to the high rates of obesity, insulin resistance, and therefore, potential risk of type 2 diabetes (T2D) and breast cancer. Mexican immigrants may be evolutionary adapted to traditional diets high in legumes and complex carbohydrates. When consuming an inexpensive, readily available U.S. diet high in refined carbohydrates and added sugars they may experience a detrimental metabolic and/or inflammatory response, placing them at a disproportionately higher risk of certain cancers. To better understand these biological mechanisms that may underlie immigrant-related health disparities, we tested whether genetic ancestry modified the metabolic response to a traditional Mexican versus U.S. diet in a controlled feeding trial.

Methods: First and second generation, female, Mexican immigrants (n=53) completed a randomized, crossover feeding trial testing the response to a Mexican versus U.S. diet for 24 days each, separated by a 28-day washout period. The trial diets were designed to provide energy content for weight maintenance and were similar in macronutrient composition. Participants were instructed to consume only study provided foods. The traditional Mexican diet was high in corn tortillas, beans, Mexican soups, fruits, vegetables, animal fats, full-fat milk, and Mexican cheeses; in contrast, the U.S. diet was high in refined carbohydrates, vegetable oils, nonfat or low-fat milk, processed foods, processed meats and sugar-sweetened beverages. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor (IGF)-1, IGF binding protein (IGFBP)-3, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6), and the calculated homeostasis model assessment of insulin resistance (HOMA-IR) at the beginning and end of each feeding period. DNA was extracted from baseline blood for genotyping and estimation of each participant's proportion of genetic ancestry from four populations – Indigenous American (IA), European, African, and Asian – with the use of 218 Informative Ancestry Markers. Linear mixed models were adjusted for diet sequence, feeding period, baseline and washout biomarker concentrations, age, body weight, and acculturation.

Results: The overall genetic ancestral background of the study sample was 53% IA and 36% European ancestry. In general, genetic ancestry did not modify the metabolic responses to the Mexican versus U.S. diet. However, genetic ancestry was associated with some baseline participant's characteristics and measures. Greater IA ancestry trended toward a positive association with waist-to-hip ratio (P=0.08) and was inversely associated with both education and acculturation (P<0.05). Further, greater IA ancestry was positively associated with baseline fasting serum concentrations of glucose, CRP, IL-6, and calculated HOMA-IR (P<0.05), and was inversely associated with circulating concentrations of IGF-1 and IGFBP-3 (P<0.05).

Conclusions: Genetic ancestry suggested differences in baseline measures of several biomarkers that have been identified as cancer susceptibility biomarkers. Although, we found a significant metabolic response to the traditional Mexican versus U.S. diet, overall, we did not observe correlations between genetic ancestry and this response. Nonetheless, the results from the study may inform our understanding of variation in cancer susceptibility biomarkers in vulnerable populations. Additional research is needed to further investigate whether genetic ancestry modifies the associations of other lifestyle exposures, such as physical activity or smoking, with cancer susceptibility biomarkers in Mexican immigrants and other minority groups.

Citation Format: Margarita Santiago-Torres, Jean De Dieu Tapsoba, Mario Kratz, Johanna W. Lampe, Kara L. Breymeyer, Lisa Levy, Xiaoling Song, Adriana Villaseñor, Ching-Yun Wang, Christopher Carlson, Marian L. Neuhouser. Does genetic ancestry influence the metabolic response to a traditional Mexican versus U.S. diet? A randomized crossover feeding trial among first and second generation women of Mexican descent. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A68.