title: Associations of anthropometric factors with KRAS and BRAF mutation status of primary colorectal cancer in men and women: a cohort study.
abstract: Obesity is a well-established risk factor for colorectal cancer (CRC), and accumulating evidence suggests a differential influence of sex and anthropometric factors on the molecular carcinogenesis of the disease. The aim of the present study was to investigate the relationship between height, weight, bodyfat percentage, waist- and hip circumference, waist-hip ratio (WHR), body mass index (BMI) and CRC risk according to KRAS and BRAF mutation status of the tumours, with particular reference to potential sex differences. KRAS and BRAF mutations were analysed by pyrosequencing in tumours from 494 incident CRC cases in the Malmö Diet and Cancer Study. Hazard ratios of CRC risk according to anthropometric factors and mutation status were calculated using multivariate Cox regression models. While all anthropometric measures except height were associated with an increased risk of KRAS-mutated tumours, only BMI was associated with an increased risk of KRAS wild type tumours overall. High weight, hip, waist, WHR and BMI were associated with an increased risk of BRAF wild type tumours, but none of the anthropometric factors were associated with risk of BRAF-mutated CRC, neither in the overall nor in the sex-stratified analysis. In men, several anthropometric measures were associated with both KRAS-mutated and KRAS wild type tumours. In women, only a high WHR was significantly associated with an increased risk of KRAS-mutated CRC. A significant interaction was found between sex and BMI with respect to risk of KRAS-mutated tumours. In men, all anthropometric factors except height were associated with an increased risk of BRAF wild type tumours, whereas in women, only bodyfat percentage was associated with an increased risk of BRAF wild type tumours. The results from this prospective cohort study further support an influence of sex and lifestyle factors on different pathways of colorectal carcinogenesis, defined by KRAS and BRAF mutation status of the tumours.
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Brändstedt
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden.
authors.forename: Sakarias
authors.initials: S
authors.lastname: Wangefjord
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Sundström
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, Malmö, Sweden; Department of Plastic Surgery, Skåne University Hospital, Malmö, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000150:complications; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D012737:Sex Factors; D049629:Waist-Hip Ratio; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins