Associations of anthropometric factors with KRAS and BRAF mutation status of primary colorectal cancer in men and women: a cohort study

• Published in: PloS one 2014-06, Vol.9 (2), p.e98964
• Main Authors: Brändstedt, Jenny, Wangefjord, Sakarias, Nodin, Björn, Eberhard, Jakob, Sundström, Magnus, Manjer, Jonas, Jirström, Karin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alcohol use; Analysis; Anthropometry; Biology and Life Sciences; Body mass; Body Mass Index; Body measurements; Body size; Cancer; Cancer and Oncology; Cancer och onkologi; Cancer research; Carcinogenesis; Carcinogens; Clinical Medicine; Cohort analysis; Cohort Studies; Colon; Colon - metabolism; Colon - pathology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Diet; Female; Gender aspects; Gender differences; Gene mutation; Genetic aspects; Health risk assessment; Health risks; Hip; Humans; K-Ras protein; Klinisk medicin; Male; Medical and Health Sciences; Medical prognosis; Medicin och hälsovetenskap; Medicine and Health Sciences; Men; Middle Aged; Mortality; Mutation; Nutrition research; Obesity; Obesity - complications; Oncology; Pathology; People and Places; Proportional Hazards Models; Proto-Oncogene Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins; ras Proteins - genetics; Regression analysis; Regression models; Research and Analysis Methods; Research Support, Non-U.S. Gov't; Risk Factors; Sex; Sex differences; Sex Factors; Studies; Surgery; Tumors; Waist-Hip Ratio; Women
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098964

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.