Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts

Abstract

Objective: To investigate whether the positive association of body mass index (BMI, kg/m(2)) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes.

Methods: In a pooled analysis of primary data of seven prospective cohorts including 458,070 men and 485,689 women, we identified 2,454 patients with incident pancreatic cancer during an average 6.9 years of follow-up. Cox proportional hazard regression models were used in data analysis.

Results: In a random-effects meta-analysis, for every 5 kg/m(2) increment in BMI, the summary relative risk (RR) was 1.06 (95% confidence interval (CI) 0.99-1.13) for men and 1.12 (95% CI 1.05-1.19) for women. The aggregate analysis showed that compared with normal weight (BMI: 18.5 to <25), the adjusted RR was 1.13 (95% CI 1.03-1.23) for overweight (BMI: 25 to <30) and 1.19 (95% CI 1.05-1.35) for obesity class I (BMI: 30 to <35). Tests of interactions of BMI effects by other risk factors were not statistically significant. Every 5 kg/m(2) increment in BMI was associated with an increased risk of pancreatic cancer among never and former smokers, but not among current smokers (P-interaction = 0.08).

Conclusion: The present evidence suggests that a high BMI is an independent risk factor of pancreatic cancer.

Fig. 1

Relative risk of pancreatic cancer per 5 kg/m² increment in body mass index in the individual studies with the summary relative risk estimates. Diamonds indicate the summary relative risk and its 95% confidence interval. Test of between-study heterogeneity: P = 0.997, 0.628, and 0.899 for all participants, men and women, respectively

Fig. 2

Relative risk of pancreatic cancer per 2.5 kg/m² increment of body mass index using 22.5–25 as the referent group (P for trend 0.02). The number of cases was 17, 41, 294, 520, 705, 404, 250, 131, 71, and 21 for each BMI category along the X axis from left to right. We placed the dots for 8% increase of risk per 5 kg/m² increment in body mass index at 18.8, 23.8, 28.8, 33.8, 38.8 and 43.8 of body mass index and drew a super-imposed dashed line. This figure shows that in the aggregate analysis, the summary relative risk per 5 kg/m² increment of body mass index is the approximation to the risk estimate by the categorical analysis