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Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases.

ABSTRACT: BACKGROUND: The majority of non-syndromic colorectal cancers (CRCs) can be described as a complex disease. A two-stage case-control study on CRC susceptibility was conducted to assess the influence of the ancestral alleles in the polymorphisms previously associated with nutrition-related complex diseases. METHODS: In stage I, 28 single nucleotide polymorphisms (SNPs) were genotyped in a hospital-based Czech population (1025 CRC cases, 787 controls) using an allele-specific PCR-based genotyping system (KASPar(®)). In stage II, replication was carried out for the five SNPs with the lowest p values. The replication set consisted of 1798 CRC cases and 1810 controls from a population-based German study (DACHS). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between genotypes and CRC risk were estimated using logistic regression. To identify signatures of selection, Fay-Wu's H and Integrated Haplotype Score (iHS) were estimated. RESULTS: In the Czech population, carriers of the ancestral alleles of AGT rs699 and CYP3A7 rs10211 showed an increased risk of CRC (OR 1.26 and 1.38, respectively; two-sided p?0.05), whereas carriers of the ancestral allele of ENPP1 rs1044498 had a decreased risk (OR 0.79; p?0.05). For rs1044498, the strongest association was detected in the Czech male subpopulation (OR 0.61; p=0.0015). The associations were not replicated in the German population. Signatures of selection were found for all three analyzed genes. CONCLUSIONS: Our study showed evidence of association for the ancestral alleles of polymorphisms in AGT and CYP3A7 and for the derived allele of a polymorphism in ENPP1 with an increased risk of CRC in Czechs, but not in Germans. The ancestral alleles of these SNPs have previously been associated with nutrition-related diseases hypertension (AGT and CYP3A7) and insulin resistance (ENPP1). Future studies may shed light on the complex genetic and environmental interactions between different types of nutrition-related diseases.

SUBMITTER: Huhn S

PROVIDER: S-EPMC3522999 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases.

Huhn Stefanie S Bevier Melanie M Rudolph Anja A Pardini Barbara B Naccarati Alessio A Hein Rebecca R Hoffmeister Michael M Vodickova Ludmila L Novotny Jan J Brenner Hermann H Chang-Claude Jenny J Hemminki Kari K Vodicka Pavel P Försti Asta A

BMC medical genetics 20121005

<h4>Background</h4>The majority of non-syndromic colorectal cancers (CRCs) can be described as a complex disease. A two-stage case-control study on CRC susceptibility was conducted to assess the influence of the ancestral alleles in the polymorphisms previously associated with nutrition-related complex diseases.<h4>Methods</h4>In stage I, 28 single nucleotide polymorphisms (SNPs) were genotyped in a hospital-based Czech population (1025 CRC cases, 787 controls) using an allele-specific PCR-based ...[more]

PMID: 23036011

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Project description: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.

Project description:Despite many significant advances in treatment and management, cardiovascular disease remains the main cause of the global disease burden. Nutrition-related disease is a modifiable cardiovascular risk factor. However, few studies have examined the relationship between nutrition-related diseases and cardiovascular mortality. We aimed to investigate the association of nutrition-related diseases with cardiovascular mortality based on a large nationally representative community population. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 with mortality follow-up through December 31, 2015. Finally, 12,469 participants were analyzed. Each participant was assigned to one of four groups: normal nutrition without sarcopenia, sarcopenia with normal nutrition, malnutrition without sarcopenia, and malnutrition-sarcopenia syndrome. Survival curves and Cox regressions based on the NHANES recommended weights were used to assess the association between nutrition-related diseases and cardiovascular mortality. Of the 12,469 patients included in the study and divided into four groups, malnutrition-sarcopenia syndrome had the highest 5- and 10-year cardiovascular mortality rates. After adjustment for related factors, sarcopenia with normal nutrition (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.28-2.06; P < 0.001), malnutrition without sarcopenia (HR: 1.28, 95% CI:1.03-1.58; P = 0.024), and malnutrition-sarcopenia syndrome (HR: 2.66, 95% CI:1.89 - 3.74; P < 0.001) were significantly associated with increased risk of all-cause mortality. Malnutrition-sarcopenia syndrome remained associated with an increased risk of cardiovascular mortality (HR: 3.56, 95% CI: 1.17 - 10.84; P < 0.001). Malnutrition-sarcopenia syndrome was highly prevalent among community-dwelling adults in the United States and was a strong prognostic factor for cardiovascular mortality in the community setting. Randomized clinical trials are needed to demonstrate whether prevention or treatment of malnutrition-sarcopenia syndrome in community populations can reduce global cardiovascular mortality.

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Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases.

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Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases.

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