Candidate Genetic Loci Modifying the Colorectal Cancer Risk Caused by Lifestyle Risk Factors.

IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Shabane Barot, Litika Vermani, Johannes Blom, Susanna Larsson, Annelie Liljegren, Annika Lindblom
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引用次数: 0

Abstract

Introduction: 65%-70% of colorectal cancer (CRC) cases are considered sporadic; they arise under the influence of environmental factors in individuals lacking a family history of CRC. Low-risk genetic variants are believed to contribute to CRC risk, in tandem with lifestyle factors.

Methods: Six hundred sixteen nonfamilial Swedish CRC cases with at least 1 of the following 5 risk factors: smoking, excessive alcohol consumption, physical inactivity, adherence to an unhealthy diet, and excess body weight were included in this study. A control group consisting of 1,642 healthy individuals was used. Cases and controls were genotyped from blood samples at the Centre for Inherited Disease Research at Johns Hopkins University within the Colorectal Transdisciplinary Study research collaboration, using the Illumina Infinium OncoArray-500 K BeadChip. Five separate genome-wide haplotype association analyses were performed, one for each risk factor. Logistic regression models were used to estimate associations between haplotypes (exposure) and CRC (outcome) in cases with lifestyle risk factors vs controls. Haplotypes with an odds ratio >1 were considered candidate risk markers, denoting an area of interest in the genome. A significance threshold of P < 5 × 10-8 was used.

Results: We found 17 haplotype regions significantly associated with CRC in cases vs controls. Several regions included genes linked to inflammation and tumor promotion.

Discussion: We concluded that having certain genetic variants was associated with an increased risk of CRC compared with healthy controls among cases with known lifestyle risk factors. The interplay of lifestyle and genetic risk factors calls for further elucidation.

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来源期刊
Clinical and Translational Gastroenterology
Clinical and Translational Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
7.00
自引率
0.00%
发文量
114
审稿时长
16 weeks
期刊介绍: Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease. Colon and small bowel Endoscopy and novel diagnostics Esophagus Functional GI disorders Immunology of the GI tract Microbiology of the GI tract Inflammatory bowel disease Pancreas and biliary tract Liver Pathology Pediatrics Preventative medicine Nutrition/obesity Stomach.
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