Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
PLoS One. 2011 Apr 5;6(4):e18571. doi: 10.1371/journal.pone.0018571.
We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC).
In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.3 years of follow-up, 603 cases and 4,631 sub-cohort members were available. CIMP status according to the Weisenberger markers was determined using methylation specific PCR on DNA from paraffin embedded tumor tissue. Hazard rate ratios (HR) and 95% confidence intervals for CIMP (27.7%) and non-CIMP (72.3%) tumors were calculated according to BMI, BMI at age 20, BMI change, trouser/skirt size, height, and physical activity.
BMI modeled per 5 kg/m(2) increase was associated with both CIMP and non-CIMP tumors, however, HRs were attenuated when additionally adjusted for trouser/skirt size. Trouser/skirt size, per 2 size increase, was associated with both tumor subtypes, even after adjustment for BMI (CIMP HR: 1.20, 95%CI: 1.01-1.43; non-CIMP HR: 1.14, 95%CI: 1.04-1.28). Height per 5 cm was associated with both tumor sub-types, but HRs were attenuated when adjusted for body weight. BMI at age 20 was positively associated with increased risk of CIMP tumors and the association was significantly less pronounced for non-CIMP tumors (P-heterogeneity = 0.01). Physical activity was inversely associated with both subtypes, but a dose-response association was observed only for non-CIMP tumors (P-trend = 0.02).
Body size, especially central adiposity, may increase the risk of both CIMP and non-CIMP tumors. Body fat at young age may differentially influence risk. Physical activity appears to decrease the risk of CRC regardless of these molecular subtypes.
我们研究了体型和身体活动如何影响结直肠癌（CRC）中 CpG 岛甲基化表型（CIMP）的风险。
在荷兰队列研究（n=120852）中，风险因素于 1986 年在基线时自我报告。经过 7.3 年的随访，603 例病例和 4631 名亚队列成员可用。使用石蜡包埋肿瘤组织的甲基化特异性 PCR 确定基于 Weisenberger 标志物的 CIMP 状态。根据 BMI、20 岁时的 BMI、BMI 变化、裤/裙尺寸、身高和身体活动计算 CIMP（27.7%）和非 CIMP（72.3%）肿瘤的危险率比（HR）和 95%置信区间。
BMI 每增加 5kg/m2 与 CIMP 和非 CIMP 肿瘤均相关，但当额外调整裤/裙尺寸时 HR 减弱。裤/裙尺寸每增加 2 个尺寸，与两种肿瘤亚型均相关，即使在调整 BMI 后也是如此（CIMP HR：1.20，95%CI：1.01-1.43；非 CIMP HR：1.14，95%CI：1.04-1.28）。身高每增加 5cm 与两种肿瘤亚型均相关，但当调整体重时 HR 减弱。20 岁时的 BMI 与 CIMP 肿瘤的风险增加呈正相关，而非 CIMP 肿瘤的相关性明显减弱（P 异质性=0.01）。身体活动与两种亚型均呈负相关，但仅在非 CIMP 肿瘤中观察到剂量反应关联（P 趋势=0.02）。
体型，尤其是中心性肥胖，可能会增加 CIMP 和非 CIMP 肿瘤的风险。年轻时的体脂可能会以不同的方式影响风险。无论这些分子亚型如何，身体活动似乎都能降低 CRC 的风险。
