| Background and objectiveOverweight and obesity has risen substantially worldwide and has become a major global health challenge.During the past two decades,China has also experienced an increasing trend in the prevalence of overweight and obesity as a result of socioeconomic development and dramatic lifestyle changes;however,underweight remains prevalent in certain areas.Previous studies have established associations between body mass index(BMI,a measure of overall body fatness)and several cancers,but the evidence is mainly limited to Caucasians.Body fatness may vary in different populations,moreover,the cancer pattern and relating risk factors are significantly different between China and Western countries,all of which can lead to different BMI-cancer associations.Several case-control studies have focused on the associations between BMI and incidence of major cancers in China,but convincing result from prospective cohort studies is still lacking.In addition,the existed studies mainly used BMI as a measure of body fatness.Although BMI is a widely used in field epidemiology studies,it depends only on height and weight and has limitations in reflecting adipose tissue and muscle mass.Few data are available regarding cancer risk prediction based on different anthropometric measures.In this present study,we aimed to examine the relationship between body fatness,with different anthropometric measures,and cancer incidence for overall cancer and for 15 common cancer sites in a large population from multi areas in China.We further compared the cancer predict ability of different anthropometric measures,and estimated the cancer burden that was attributed to overweight or obesity and underweight in China.Subjects and methodsData used in this study were from China Kadoorie Biobank(CKB),a large population-based cohort study that interviewed between June,2004 and July,2008.A total of 512,891 adults aged 30-79 years were recruited from 10 geographically diverse areas in China.The participants were interviewed using laptop-based questionnaires at baseline to collect data on demographic and socioeconomic statuses,smoking and alcohol consumption,physical activity,self-reported medical history and reproductive history(in women).Anthropometric measures of body fatness were measured according to a standard protocol.Data on cancer incidence were collected through linkages with established chronic disease registries in the study areas and with the national health insurance claim databases,and were coded by the 10th International Classification of Diseases(ICD-10).To help improve the accuracy of diagnosis,outcome adjudication and further reviews of hospital medical notes were conducted.After excluding participants with cancers at baseline and incident cancers diagnosed during the first 12 months of follow-up,a total of 508,362 participants aged 35-79 years were included in the subsequent analysis.Based on WHO's criteria,BMI was classified into four categories:underweight(BMI<18.5kg/m~2),normal weight(18.5?BMI<25.0kg/m~2),overweight(25.0?BMI<30.0kg/m~2)and obesity(BMI?30.0kg/m~2).The crude cancer incidence rates were standardized by age,sex and region(urban/rural)using population composition from2010 Chinese census population.Cox proportional hazards regression models were used to estimate the associations between different anthropometric measures,including BMI,body fat percentage(BFP),waist circumference(WC)and waist-to-hip ratio(WHR),and the incidence of overall cancer and each cancer site of interest.Hazard ratios(HRs)were fitted with adjustment for education level,marital status,annual household income,alcohol consumption,smoking status and physical activity,and with stratification according to age at risk(in 5 year intervals),sex,and region(10 study sites).Subgroup analyses for selected cancer sites were performed to estimate the consistency of the relationship when appropriate,according to sex,area,age at risk,menopause status,smoking status,alcohol drinking status or total physical activity.Modification effects of the stratified variables were evaluated,respectively,by the interaction terms with BMI spline variables,which were further examined using the likelihood test compared to the model without interaction terms.To examine the robustness of our findings,we also conducted several sensitivity analyses.Furthermore,receiver operator characteristic(ROC)curves and area under the curve(AUC)for different anthropometric measures were calculated to compare their predictive ability.For specific cancer sites associated with BMI,we additionally calculated the population attributed fraction(PAF)to estimate the cancer burden attributed to overweight/obesity or underweight in China.ResultsThe mean age of 508,362 participants at recruitment was 51.47±10.67 years.There were 208,247(40.96%)male participants,of whom the mean BMI was23.44±3.25kg/m~2 and 300,115(59.04%)female participants,of whom the mean BMI was 23.81±3.46 kg/m~2.According to the WHO's criterion,28.87%of the participants were overweight and 4.08%were obesity,in comparison,4.32%of the participants were underweight.BMI,BFP,WC and WHR were positively correlated with one another,but the distribution patterns based on sex and region were substantially different as the age increased.During an average of 8.94 years of follow-up,21,474incident cancers were identified.The standardized incidence rate(SIR)of all cancer combined was 460.01 per 100,000 person years(PY).Lung cancer(SIR:99.40 per100,000 PY)was the most frequently diagnosed cancer in men,followed by liver(SIR:67.20 per 100,000 PY),gastric(SIR:64.13 per 100,000 PY),oesophageal(SIR:51.51 per 100,000 PY)and colorectal(SIR:46.03 per 100,000 PY)cancer.Breast cancer(SIR:83.41 per 100,000 PY)was the most frequently diagnosed cancer in women,followed by lung(SIR:46.25 per 100,000 PY),cervical(SIR:41.36 per100,000 PY),colorectal(SIR:35.76 per 100,000 PY)and liver(SIR:24.48 per100,000 PY)cancer.Compared with participants with normal weight,significant associations were observed for overweight and obesity participants with risk of endometrial(HR=1.77,95%CI:1.35 to 2.32 for overweight and HR=4.23,95%CI:2.93 to 6.12 for obesity,respectively),postmenopausal breast(HR=1.22,95%CI:1.08 to 1.39 and HR=1.70,95%CI:1.38 to 2.10)and colorectal cancer(HR=1.19,95%CI:1.08 to 1.31 and HR=1.34,95%CI:1.11 to 1.62).A significant increased risk of oesophageal(HR=1.51,95%CI:1.24 to 1.85),lung(HR=1.45,95%CI:1.29 to 1.64)and gastric cancer(HR=1.41,95%CI:1.18 to 1.68),and a borderline risk of liver cancer(HR=1.22,95%CI:1.00 to 1.48)were observed for underweight participants.Each 5kg/m~2 increase in BMI was associated with an increased risk of endometrial(HR=2.01,95%CI:1.72 to 2.35),postmenopausal breast(HR=1.29,95%CI:1.18 to1.40),colorectal(HR=1.17,95%CI:1.10 to 1.25)and cervical(HR=1.15,95%CI:1.03 to1.29)cancer,whereas it was associated with a reduced risk of oesophageal(HR=0.73,95%CI:0.67 to 0.79),lung(HR=0.78,95%CI:0.74 to 0.82),liver(HR=0.85,95%CI:0.79 to 0.92),and gastric(HR=0.88,95%CI:0.82 to 0.94)cancer.The associations remained stable in non-current smokers and during sensitivity analyses.The results of BFP,WC and WHR are largely in line with that of BMI,but other anthropometric measures may add value to site-specific cancer risk prediction.BMI was the best risk predictor for endometrial(AUC=0.64,95%CI:0.61 to 0.67)and postmenopausal breast cancer(AUC=0.58,95%CI:0.56 to 0.59);BFP did for oesophageal(AUC=0.65,95%CI:0.63 to 0.66),liver(AUC=0.64,95%CI:0.62 to0.65),gastric(AUC=0.63,95%CI:0.62 to 0.64)and lung cancer(AUC=0.61,95%CI:0.60 to 0.62);and WC and WHR did for colorectal cancer(AUC=0.57,95%CI:0.56 to 0.59 and AUC=0.58,95%CI:0.56 to 0.58,respectively)Based on the effect size of BMI observed in the current study,we estimated that26,720 endometrial(PAF=33.59%),18,404 colorectal(PAF=6.51%),10,728postmenopausal breast(PAF=9.51%)and 2,656 cervical(PAF=4.08%)cancer were attributable to overweight and obesity in China.The number of new patients being affected by these four cancers is predicted to increase to 100,000 by 2025.The PAFs of underweight were bwtween 4.15-1.84%for oesophageal,lung,gastric and liver cancer.Being underweight might lead to approximately 60,000 new incident cancers by 2025.ConclusionBody fatness is related to cancer incidence in China,with different site-specific associations.Overweight and obesity are associated with an increased risk of endometrial,postmenopausal breast,colorectal and cervical cancer,while underweight is associated with an increased risk of oesophageal,lung,liver and gastric cancer.Either high or low body fatness contributes to the incidence of different types of cancer in China.Our study provides additional epidemiological information into preventing cancer occurrence through reducing excess body fatness and maintaining moderate body fatness. |
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