Christakoudi Sofia, Tsilidis Konstantinos K, Gunter Marc J, Riboli Elio
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Cancer Med. 2025 Mar;14(6):e70809. doi: 10.1002/cam4.70809.
Obesity and diabetes are positively associated with pancreatic cancer risk. It is unclear, however, whether fat or fat-free mass plays a role in these relationships, whether abdominal obesity is more important than general obesity or whether the associations with anthropometric indices and diabetes are independent of each other.
We used multivariable Cox proportional hazards models to examine the prospective associations of body composition (allometric fat-mass index (AFI) and allometric lean-mass index (ALI), based on bioelectrical impedance, uncorrelated with each other and with height), waist size (allometric waist-to-hip index (WHI), uncorrelated with weight and height) and diabetes with pancreatic cancer risk in UK Biobank. We tested heterogeneity by sex, age and follow-up time with the augmentation method (p_het).
During a mean follow-up of 10.4 years, 999 pancreatic cancer cases were ascertained in 427,939 participants. AFI was positively associated with pancreatic cancer risk in participants overall, independent of ALI, WHI, diabetes and covariates (hazard ratio HR = 1.102; 95% confidence interval CI = 1.033-1.176 per 1 standard deviation (SD) increase), more strongly in women aged under 55 years at recruitment (HR = 1.457; 95% CI = 1.181-1.797; p_het = 0.007) and in men only for follow-up 6 years or longer (HR = 1.159; 95% CI = 1.037-1.295; p_het = 0.075). ALI was positively associated with pancreatic cancer risk in participants overall (HR = 1.072; 95% CI = 1.005-1.145), more specifically in men (HR = 1.132; 95% CI = 1.035-1.238; p_het = 0.091). A positive association of WHI with pancreatic cancer risk was observed only in unadjusted models but was lost after adjustment for smoking status and diabetes. Independent of anthropometric indices, diabetes was associated positively with pancreatic cancer risk in participants overall (HR = 1.688; 95% CI = 1.365-2.087), but in women only for follow-up under 6 years (HR = 2.467; 95% CI = 1.477-4.121; p_het = 0.042).
General obesity (reflected in AFI and ALI) and diabetes but not abdominal obesity were associated positively with pancreatic cancer risk, independent of each other and covariates.
肥胖和糖尿病与胰腺癌风险呈正相关。然而，尚不清楚脂肪或去脂体重在这些关系中是否起作用，腹部肥胖是否比全身肥胖更重要，以及与人体测量指标和糖尿病的关联是否相互独立。
我们使用多变量Cox比例风险模型，在英国生物银行中研究身体成分（基于生物电阻抗的异速生长脂肪量指数（AFI）和异速生长瘦体重指数（ALI），彼此不相关且与身高不相关）、腰围（异速生长腰臀比指数（WHI），与体重和身高不相关）和糖尿病与胰腺癌风险的前瞻性关联。我们使用增强法（p_het）按性别、年龄和随访时间检验异质性。
在平均10.4年的随访期间，427,939名参与者中确诊了999例胰腺癌病例。AFI与总体参与者的胰腺癌风险呈正相关，独立于ALI、WHI、糖尿病和协变量（风险比HR = 1.102；95%置信区间CI = 1.033 - 1.176，每增加1个标准差（SD）），在招募时年龄小于55岁的女性中更强（HR = 1.457；95% CI = 1.181 - 1.797；p_het = 0.007），在男性中仅随访6年或更长时间时呈正相关（HR = 1.159；95% CI = 1.037 - 1.295；p_het = 0.075）。ALI与总体参与者的胰腺癌风险呈正相关（HR = 1.072；95% CI = 1.005 - 1.145），更具体地在男性中（HR = 1.132；95% CI = 1.035 - 1.238；p_het = 0.091）。仅在未调整模型中观察到WHI与胰腺癌风险呈正相关，但在调整吸烟状态和糖尿病后这种相关性消失。独立于人体测量指标，糖尿病与总体参与者的胰腺癌风险呈正相关（HR = 1.688；95% CI = 1.365 - 2.087），但仅在女性随访时间不足6年时呈正相关（HR = 2.467；95% CI = 1.477 - 4.121；p_het = 0.042）。
全身肥胖（反映在AFI和ALI中）和糖尿病而非腹部肥胖与胰腺癌风险呈正相关，彼此独立且与协变量无关。
