病例对照研究超重、肥胖与结直肠癌风险的关系，总体分析及肿瘤微卫星不稳定状态分层分析。
Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status.
机构信息
Epidemiology Research Program, American Cancer Society, National Home Office, 250 Williams St NW, Atlanta, GA 30303, USA.
出版信息
J Natl Cancer Inst. 2010 Mar 17;102(6):391-400. doi: 10.1093/jnci/djq011. Epub 2010 Mar 5.
BACKGROUND
Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.
METHODS
The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (> or =30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.
RESULTS
Recent BMI, modeled in 5 kg/m(2) increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P = .22). Recent BMI, per 5 kg/m(2), was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).
CONCLUSION
The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.
背景
超重或肥胖是结直肠癌的既定危险因素，男性比女性更为明显。大约 10%-20%的结直肠肿瘤表现出微卫星不稳定性（MSI），定义为肿瘤组织中与附近正常组织相比，小重复序列的扩展或收缩。我们评估了超重或肥胖与结直肠癌风险之间的关联，包括整体和肿瘤 MSI 状态。
方法
该研究包括 1794 名通过人群癌症登记处确定的结直肠癌病例受试者和 2684 名与其无病的性别匹配的兄弟姐妹作为对照受试者。最近的体重指数（BMI）、20 岁时的 BMI 和成年体重变化是根据身高和体重的自我报告得出的。对 69.7%的病例受试者进行了多达 10 个标志物的肿瘤 MSI 状态评估，并将其分类为微卫星（MS）稳定（0%的标志物不稳定；n=913）、MSI-低（>0%但 <30%的标志物不稳定；n=149）或 MSI-高（>或=30%的标志物不稳定；n=188）。多变量条件逻辑回归用于估计比值比（OR）和 95%置信区间（95%CI）。所有统计检验均为双侧。
结果
最近的 BMI 以 5kg/m2 为增量进行建模，与男性和女性结直肠癌风险呈正相关（OR=1.24；95%CI=1.15 至 1.34），仅与女性（OR=1.20；95%CI=1.10 至 1.32），仅与男性（OR=1.30；95%CI=1.15 至 1.47）。与性别无交互作用（P=0.22）。最近的 BMI 每增加 5kg/m2，与 MS 稳定（OR=1.38；95%CI=1.24 至 1.54）和 MSI-低（OR=1.33；95%CI=1.04 至 1.72）结直肠肿瘤的风险呈正相关，但与 MSI-高肿瘤（OR=1.05；95%CI=0.84 至 1.31）的风险无关。
结论
与高 BMI 相关的结直肠癌风险增加可能主要局限于表现出更常见的 MS 稳定表型的肿瘤，这表明结直肠癌的病因因肿瘤 MSI 状态而异。
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