Correlation between breast cancer and lifestyle within the Gulf Cooperation Council countries: A systematic review

BACKGROUNDIn the six Gulf Cooperation Council countries (GCCCs), Bahrain, Saudi Arabia, Kuwait, Oman, Qatar and the United Arab Emirates, breast cancer (BC) is the greatest cause of cancer incidence and mortality. Obesity and physical inactivity are established risk factors for BC globally and appear to be more of a problem in high income countries like the GCCCs.AIMTo determine whether obesity and physical inactivity are associated with BC incidence in the GCCCs using the United Kingdom as a comparator. METHODSThis systematic review was carried out according to PRISMA guidelines. A cancer registry and a statistical data search was done to identify the BC incidence over the past two decades and the prevalence of obesity and physical inactivity in the GCCCs. Additionally, a systematic search of the databases, MEDLINE, Web of Science, and PubMed between 1999 and 2019 was performed to determine whether obesity and physical inactivity are risk factors for BC in the GCCCs. All papers were critically appraised according to their research methods and were assessed for quality and risk of bias.RESULTSBC was the top malignancy in each GCC country. Women tended to be diagnosed with BC at a younger age than women in the United Kingdom. The greatest 10-year increase in BC incidence was seen in Saudi Arabia (54.2%), approximately seven times the rate of increase seen in the United Kingdom (7.6%). The prevalence of obesity and physical inactivity was greater in all the GCCCs in comparison to the United Kingdom. A total of 155 full studies were reviewed of which 17 were included. Of those, eight looked at the prevalence of obesity and physical inactivity in the Gulf States and nine looked at these as risk factors for BC. Only one study found an association between BC and obesity (odds ratio = 2.29). No studies looked solely at the link between physical inactivity and BC.CONCLUSIONThe prevalence of obesity and physical inactivity was high within the GCCCs, but the majority of the included studies found no positive correlation between obesity or physical inactivity and BC. A high proportion of women in this study were pre-menopausal which could contribute to the negative findings

Gene-By-Diet Interactions And Obesity Among Yup'ik People Living In Southwest Alaska

Thesis (Ph.D.) University of Alaska Fairbanks, 2012BACKGROUND: Molecular approaches have expedited the discovery of human obesity genes, however the heritability explained by these loci remains low (<2%). Gene-by-environment interactions may partially account for the "missing heritability" attributed to variation in obesity phenotypes. OBJECTIVE: The specific aims of this dissertation were to (i) identify genetic polymorphisms associated with obesity-related phenotypes in Yup'ik people and (ii) evaluate how n-3 polyunsaturated fatty acid (n-3 PUFA) intake modifies associations between genetic polymorphisms and obesity-related phenotypes in a population with widely varying intake of n-3 PUFAs. APPROACH: We genotyped genetic polymorphisms in (1) candidate genes with a strong physiological role in obesity pathophysiology; (2) candidate genes identified in obesity whole-genome linkage studies that were regulated by n-3 PUFAs; and (3) candidate genes reproducibly implicated in obesity genome-wide association studies (GWAS). DATA & ANALYSES: We used Center for Alaska Native Health Research (CANHR) data collected between 2001 and 2008. We estimated dietary intake of n-3 PUFA using nitrogen stable isotope ratios (delta15N) of red blood cells (RBC) and obesity-related phenotypes were obtained by trained staff. Genotype-phenotype analyses used generalized linear models that accounted for familial correlations. RESULTS: Our analyses of candidate genes based on physiology revealed a polymorphism called P479L in carnitine palmitoyltransferase 1A (CPT1A) that was associated with elevated fasting HDL-cholesterol and all obesity phenotypes. Our investigation of candidate genes that are regulated by n-3 PUFAs and implicated in obesity whole-genome linkage studies demonstrate that polymorphisms in stearoyl CoA desaturase (SCD) and steroyl regulatory element binding protein (SLC2A4) were associated with obesity-related phenotypes; however n-3 PUFA intake did not modify associations between SCD and SLC2A4 polymorphisms and obesity phenotypes. Finally, our investigation of candidate genes reproducibly implicated in obesity GWAS demonstrated that genetic predisposition to obesity is associated with adiposity and that interactions with n-3 PUFA intake accounted for more than twice the phenotypic variation in adiposity. CONCLUSION: Taken together, results from this dissertation suggest that selecting candidate genes based on large-scale genomic analyses, such as linkage analyses and GWAS, has the potential to identify gene-by-environment interactions that partially account for the "missing heritability" attributed to obesity