Assessing the associations of metabolic risk factors with risk of cancer in Chinese adults: a prospective study of 0.5 million people

Abstract

Background: Metabolic risk factors are associated with higher risks of certain cancers in Western populations. Uncertainty remains about the direction, shape, and strength of their associations with specific cancers and their subtypes in China. This thesis aims to investigate the associations of major metabolic risk factors (physical activity [PA], sedentary leisure time [SLT], adiposity, diabetes, and blood glucose) with risks of pancreatic, liver, and colorectal cancer in Chinese adults. Methods: The prospective China Kadoorie Biobank (CKB) recruited 512,713 adults aged 30-79 years from 10 diverse areas of China during 2004-08. After ~10 years of follow-up, there were 26,594 incident cases of cancer, including 796 pancreatic, 2847 liver, and 3024 colorectal cancer cases among 509,892 participants with no prior history of cancer at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) of specific cancer associated with PA, SLT, adiposity, diabetes, and, among those without previously diagnosed diabetes, with levels of random plasma glucose (RPG). Results: At baseline, the mean (SD) age was 52 (10.7) years and 59% were women. The mean (SD) BMI was 23.7 (3.3) kg/m2, with 33% being overweight (BMI 25-29.9 kg/m2, 29%) or obese (BMI â¥30 kg/m2, 4%), and 5.9% had previously diagnosed (3.1%) or screen-detected (2.8%) diabetes. The mean (SD) total PA and SLT were 21.1 (13.9) metabolic equivalent of tasks (MET)-h/day and 3.0 (1.5) h/day. Total PA was inversely associated with risks of liver and colorectal cancer (HR per 4 MET-h/day: 0.95 [0.93-0.98] and 0.97 [0.94-1.00], respectively) but not with pancreatic cancer, while SLT was positively associated with risk of colorectal cancer (1.13 [1.00-1.26] per 1.5 h/day) but not with pancreatic and liver cancer. For colorectal cancer, the positive association with SLT was stronger for colon than rectal cancer (1.14 [0.98-1.32] vs 1.05 [0.89-1.23]). General (e.g. BMI) and central (e.g. waist circumference [WC]) adiposity measures were positively associated with risk of colorectal cancer (e.g. 1.13 [1.07-1.20] per 5 kg/m2 BMI and 1.17 [1.11-1.22] per 10 cm WC) but not with pancreatic cancer. The positive associations tended to be stronger for colon than rectal cancer (BMI per 5 kg/m2 1.18 [1.10-1.27] vs 1.09 [1.01-1.17]; WC per 10 cm 1.23 [1.16-1.30] vs 1.12 [1.06-1.20]). Liver cancer showed no association with BMI (1.01 [0.93-1.10]) but a positive association with WC (1.08 [1.01-1.15]) after excluding the first five years of follow-up. Diabetes (previously diagnosed or screen-detected) was associated with higher risks of all three cancers (pancreatic 1.62 [1.31-2.00], liver 1.43 [1.26-1.62], colorectal 1.16 [1.02-1.31]), and among participants without previously diagnosed diabetes there were also positive associations of RPG with risks of these cancers, even after exclusion of the first five years of follow-up. Conclusions: In this Chinese population with relatively low levels of adiposity and high levels of physical activity, metabolic risk factors showed different associations with certain common cancers and cancer subtypes, with some consistent with (e.g. diabetes, blood glucose) while others different from (e.g. physical activity, adiposity) previous findings reported in Western populations. </p