Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults.
Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults.
复制标题
DOI：
10.1016/s0140-6736(14)60892-8
复制
发表时间：
2014-08-30
期刊：
影响因子：
168.9
通讯作者：
Smeeth, Liam
中科院分区：
文献类型：
--
作者：
Bhaskaran, Krishnan;Douglas, Ian;Forbes, Harriet;dos-Santos-Silva, Isabel;Leon, David A.;Smeeth, Liam
高体重指数（BMI）易患几种部位特异性癌症，但以前尚未对所有常见癌症的风险模式进行大规模系统和详细的特征分析，以调整潜在的混杂因素。我们的目的是调查BMI和最常见的部位特异性癌症之间的联系。通过临床实践研究数据链中个人的初级保健数据和BMI数据，我们拟合了考克斯模型来研究BMI与22种最常见癌症之间的关联，并对潜在的混杂因素进行了调整。我们先拟合线性模型，然后拟合非线性（样条）模型;研究性别、绝经状态、吸烟和年龄对效应的影响;并计算群体效应。纳入了524万人; 166955人患上了感兴趣的癌症。 BMI与22种癌症中的17种相关，但影响因部位而异。BMI每增加5 kg/m2与子宫癌大致呈线性相关（风险比[HR] 1.62，99% CI 1.56 - 1.69; p<0.0001），胆囊（1·31，1·12-1·52; p<0·0001），肾脏（1·25，1·17-1·33; p<0·0001）、宫颈（1·10，1·03-1·17; p=0·00035）、甲状腺（1·09，1·00-1·19; p=0·0088）和白血病（1·09，1·05-1·13; p≤0·0001）。总体而言，BMI与肝癌（1.19，1.12 - 1.27）、结肠癌（1.10，1.07 - 1.13）、卵巢癌（1.09，1.04-1.14）和绝经后乳腺癌（1.05，1.03 - 1.07）呈正相关（均p<0.0001），但这些影响因潜在BMI或个体水平特征而异。我们估计了与前列腺癌和绝经前乳腺癌风险的负相关性，无论是总体（前列腺癌0.98，0.95 - 1.00;绝经前乳腺癌0.89，0.86 - 0.92）还是从不吸烟者（前列腺癌0.96，0.93 - 0.99;绝经前乳腺癌0.89，0.85 - 0.94）。相比之下，对于肺癌和口腔癌，我们在从不吸烟者中没有观察到相关性（肺癌0·99，0·93-1·05;口腔癌1·07，0·91-1·26）：总体上，负相关性是由当前吸烟者和既往吸烟者驱动的，可能是因为吸烟量的残余混杂。假设因果关系，41%的子宫癌和10%或更多的胆囊癌，肾癌，肝癌和结肠癌可以归因于超重。我们估计，BMI每增加1 kg/m2，每年将有3790名英国患者患上与BMI呈正相关的10种癌症之一。BMI与癌症风险相关，具有显著的人群水平影响。效应的异质性表明，不同的机制与不同的癌症部位和不同的患者亚组相关。国家健康研究所、威康信托基金会和医学研究理事会。
High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. National Institute for Health Research, Wellcome Trust, and Medical Research Council.