Brändstedt Jenny, Wangefjord Sakarias, Nodin Björn, Eberhard Jakob, Sundström Magnus, Manjer Jonas, Jirström Karin
Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden.
Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
PLoS One. 2014 Jun 11;9(2):e98964. doi: 10.1371/journal.pone.0098964. eCollection 2014.
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.
肥胖是结直肠癌（CRC）公认的风险因素，越来越多的证据表明性别和人体测量因素对该疾病的分子致癌作用有不同影响。本研究的目的是根据肿瘤的KRAS和BRAF突变状态，研究身高、体重、体脂百分比、腰围和臀围、腰臀比（WHR）、体重指数（BMI）与CRC风险之间的关系，特别关注潜在的性别差异。在马尔默饮食与癌症研究中，通过焦磷酸测序分析了494例初发CRC病例肿瘤中的KRAS和BRAF突变。使用多变量Cox回归模型计算根据人体测量因素和突变状态得出的CRC风险的风险比。除身高外，所有人体测量指标均与KRAS突变肿瘤的风险增加相关，但总体而言，只有BMI与KRAS野生型肿瘤的风险增加相关。高体重、臀围、腰围、WHR和BMI与BRAF野生型肿瘤的风险增加相关，但在总体分析和按性别分层分析中，没有任何人体测量因素与BRAF突变CRC的风险相关。在男性中，几种人体测量指标与KRAS突变和KRAS野生型肿瘤均相关。在女性中，只有高WHR与KRAS突变CRC的风险增加显著相关。在KRAS突变肿瘤风险方面，发现性别与BMI之间存在显著交互作用。在男性中，除身高外的所有人体测量因素均与BRAF野生型肿瘤的风险增加相关，而在女性中，只有体脂百分比与BRAF野生型肿瘤的风险增加相关。这项前瞻性队列研究的结果进一步支持了性别和生活方式因素对由肿瘤的KRAS和BRAF突变状态定义的结直肠癌发生不同途径的影响。
