Drake Isabel, Gullberg Bo, Sonestedt Emily, Stocks Tanja, Bjartell Anders, Wirfält Elisabet, Wallström Peter, Orho-Melander Marju
Diabetes and Cardiovascular Disease - Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Sweden.
Research Group in Nutritional Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Sweden.
Int J Cancer. 2017 Sep 15;141(6):1170-1180. doi: 10.1002/ijc.30824. Epub 2017 Jun 24.
Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44-73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow-up, and body mass index (BMI) and waist circumference (WC) at baseline. Multivariable cause-specific hazard ratios (HR) and subdistribution hazard ratios (sHR), taking into account noncancer deaths, were estimated using Cox- and competing risk regression. During follow-up (mean 17 years), 7,061 incident cancers (3,220 obesity-related cancer types) and 2,848 cancer deaths occurred. BMI and WC were associated with increased risk of obesity-related cancer incidence and cancer mortality. In T2D subjects, risk of obesity-related cancer was elevated among men (HR = 1.31, 95% CI: 1.12-1.54; sHR = 1.29, 95% CI: 1.10-1.52), and cancer mortality among both men and women (HR = 1.34, 95% CI: 1.20-1.49; sHR = 1.30, 95% CI: 1.16-1.45). There was no elevated actual risk of cancer death in T2D patients with long disease duration (sHR = 1.00, 95% CI: 0.83-1.20). There was a significant additive effect of T2D and adiposity on risk of obesity-related cancer and cancer mortality. In conclusion, detection bias may partially explain the increased risk of cancer morbidity among T2D patients. Both excess risk of competing events among patients with T2D and depletion of susceptibles due to earlier cancer detection will lower the actual risk of cancer, particularly with longer diabetes duration and at older ages.
2型糖尿病(T2D)和肥胖与多种癌症风险增加相关,但非癌症死亡的竞争风险对这些关联的影响尚不清楚。我们对马尔默饮食与癌症研究中44至73岁、基线时无癌症病史的参与者进行了前瞻性研究(n = 26,953,43%为男性)。在基线和随访期间确定T2D,并在基线时测量体重指数(BMI)和腰围(WC)。使用Cox和竞争风险回归估计考虑非癌症死亡的多变量特定病因风险比(HR)和亚分布风险比(sHR)。在随访期间(平均17年),发生了7,061例新发癌症(3,220例与肥胖相关的癌症类型)和2,848例癌症死亡。BMI和WC与肥胖相关癌症发病率和癌症死亡率增加相关。在T2D患者中,男性肥胖相关癌症风险升高(HR = 1.31,95% CI:1.12 - 1.54;sHR = 1.29,95% CI:1.10 - 1.52),男性和女性的癌症死亡率均升高(HR = 1.34,95% CI:1.20 - 1.49;sHR = 1.30,95% CI:1.16 - 1.45)。病程长的T2D患者实际癌症死亡风险未升高(sHR = 1.00,95% CI:0.83 - 1.20)。T2D和肥胖对肥胖相关癌症风险和癌症死亡率有显著的相加作用。总之,检测偏倚可能部分解释了T2D患者癌症发病率增加的风险。T2D患者中竞争事件的额外风险以及早期癌症检测导致的易感人群减少都会降低实际癌症风险,尤其是糖尿病病程较长和年龄较大时。