Brändstedt Jenny, Wangefjord Sakarias, Borgquist Signe, Nodin Björn, Eberhard Jakob, Manjer Jonas, Jirström Karin
Department of Clinical Sciences, Division of Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
J Transl Med. 2013 Nov 21;11:293. doi: 10.1186/1479-5876-11-293.
Obesity is a well established risk factor of colorectal cancer (CRC), but how body size influences risk of colorectal cancer defined by key molecular alterations remains unclear. In this study, we investigated the relationship between height, weight, body mass index (BMI), waist- and hip circumference, waist-hip ratio (WHR) and risk of CRC according to expression of beta-catenin, cyclin D1, p53 and microsatellite instability status of the tumours in men and women, respectively.
Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status was assessed in tissue microarrays with tumours from 584 cases of incident CRC in the Malmö Diet and Cancer Study. Six anthropometric factors: height, weight, BMI, waist- and hip circumference, and WHR were categorized by quartiles of baseline measurements and relative risks of CRC according to expression of beta-catenin, cyclin D1, p53 and MSI status were calculated using multivariate Cox regression models.
High height was associated with risk of cyclin D1 positive, and p53 negative CRC in women but not with any investigative molecular subsets of CRC in men. High weight was associated with beta-catenin positive, cyclin D1 positive, p53 negative and microsatellite stable (MSS) tumours in women, and with beta-catenin negative and p53 positive tumours in men. Increased hip circumference was associated with beta-catenin positive, p53 negative and MSS tumours in women and with beta-catenin negative, cyclin D1 positive, p53 positive and MSS tumours in men. In women, waist circumference and WHR were not associated with any molecular subsets of CRC. In men, both high WHR and high waist circumference were associated with beta-catenin positive, cyclin D1 positive and p53 positive tumours. WHR was also associated with p53 negative CRC, and waist circumference with MSS tumours. High BMI was associated with increased risk of beta-catenin positive and MSS CRC in women, and with beta-catenin positive, cyclin D1 positive and p53 positive tumours in men.
Findings from this large prospective cohort study indicate sex-related differences in the relationship between obesity and CRC risk according to key molecular characteristics, and provide further support of an influence of lifestyle factors on different molecular pathways of colorectal carcinogenesis.
肥胖是结直肠癌（CRC）公认的危险因素，但身体大小如何影响由关键分子改变所定义的结直肠癌风险仍不清楚。在本研究中，我们分别根据β-连环蛋白、细胞周期蛋白D1、p53的表达以及肿瘤的微卫星不稳定性状态，调查了男性和女性的身高、体重、体重指数（BMI）、腰围和臀围、腰臀比（WHR）与结直肠癌风险之间的关系。
在马尔默饮食与癌症研究中，对584例新发结直肠癌病例的肿瘤组织微阵列进行β-连环蛋白、细胞周期蛋白D1、p53的免疫组化表达及微卫星不稳定性筛查。将身高、体重、BMI、腰围和臀围、WHR这六个人体测量因素按基线测量的四分位数进行分类，并使用多变量Cox回归模型计算根据β-连环蛋白、细胞周期蛋白D1、p53表达及微卫星不稳定性状态的结直肠癌相对风险。
高身高与女性细胞周期蛋白D1阳性、p53阴性的结直肠癌风险相关，但与男性结直肠癌的任何研究分子亚组均无关。高体重与女性β-连环蛋白阳性、细胞周期蛋白D1阳性、p53阴性和微卫星稳定（MSS）肿瘤相关，与男性β-连环蛋白阴性和p53阳性肿瘤相关。臀围增加与女性β-连环蛋白阳性、p53阴性和MSS肿瘤相关，与男性β-连环蛋白阴性、细胞周期蛋白D1阳性、p53阳性和MSS肿瘤相关。在女性中，腰围和WHR与结直肠癌的任何分子亚组均无关。在男性中，高WHR和高腰围均与β-连环蛋白阳性、细胞周期蛋白D1阳性和p53阳性肿瘤相关。WHR还与p53阴性的结直肠癌相关，腰围与MSS肿瘤相关。高BMI与女性β-连环蛋白阳性和MSS结直肠癌风险增加相关，与男性β-连环蛋白阳性、细胞周期蛋白D1阳性和p53阳性肿瘤相关。
这项大型前瞻性队列研究的结果表明，根据关键分子特征，肥胖与结直肠癌风险之间的关系存在性别差异，并进一步支持生活方式因素对结直肠癌发生的不同分子途径有影响。
