The study population consisted of 314,585 men and 531,755 women among whom 1,019 men and 1,116 women developed pancreatic cancer (). Median BMI ranged from 23.6kg/m2 to 27.0kg/m2 across the studies.
Pancreatic cancer risk was increased by 47% among individuals with BMI≥30kg/m2 at baseline vs BMI between 21–22.9kg/m2 (, ). Similar risk estimates were observed for females and males. Comparing BMI ≥30kg/m2 to BMI between 21–22.9kg/m2, the results were also similar when we limited our analyses to adenocarcinomas (Ncases = 1454; pooled MVRR=1.55, 95%CI=1.28–1.89), to individuals who were not diabetic (Ncases =1651; pooled MVRR= 1.47, 95%CI=1.16–1.85) and to never smokers (Ncases =748; pooled MVRR=1.52, 95%CI=1.13–2.05). The association did not change substantially when personal history of diabetes was excluded as a covariate. When we examined BMI ≥35kg/m2 compared to BMI between 21–22.9kg/m2, we observed modestly stronger risk estimates (pooled MVRR=1.55, 95%CI =1.19–2.03).
Pooled Multivariate-Adjusted Relative Risks1 and 95% Confidence Intervals for Pancreatic Cancer According to Body Mass Index at Baseline and in Early Adulthood
Figure Multivariate Adjusted Relative Risks and 95% Confidence Intervals for Pancreatic Cancer According to BMI at Baseline (Figure a; BMI≥30kg/m2) and BMI at Younger Ages (Figure b; BMI ≥25kg/m2) compared to BMI between 21–22.9 kg/m (more ...)
As suggested by the categorical analyses, the non-parametric regression analyses showed a linear association between BMI at baseline and pancreatic cancer risk (p-value, test for non-linearity > 0.10). The pooled MVRR for a 5kg/m2 increment in BMI was 1.14 (95%CI=1.07–1.21).
The BMI-pancreatic association was similar among the different models that adjusted for smoking habits as: 1) smoking status (never, past, current), 2) smoking status and smoking duration, 3) smoking status and amount smoked, 4) smoking status, smoking duration among past smokers, and amount smoked among current smokers, or 5) smoking status and smoking pack-years (data not shown).
BMI in early adulthood was also positively (, ) and linearly (pooled MVRR=1.20, 95%CI=1.10–1.30 for a BMI increment of 5kg/m2, p-value, test for non-linearity > 0.10) associated with pancreatic cancer risk. The association between BMI in early adulthood and pancreatic cancer risk was similar when the study population was limited to non-diabetics (pooled MVRR=1.28, 95%CI=1.06–1.55), or when the case definition was limited to adenocarcinomas (pooled MVRR=1.18, 95%CI=0.95–1.47; p-value, test for trend <0.01) comparing BMI≥25 kg/m2 to BMI between 21–22.9kg/m2. The association between BMI in early adulthood and pancreatic cancer risk was stronger when the study population was limited to never smokers (pooled MVRR=1.51, 95%CI=1.13–2.01) for the same contrast. In analyses that mutually adjusted for BMI at baseline and BMI in early adulthood, we found similar risk estimates for BMI in early adulthood (pooled MVRR=1.21, 95%CI:1.04–1.45 comparing BMI≥25kg/m2 to BMI between 21–22.9kg/m2) and BMI at baseline (pooled MVRR=1.46, 95%CI:1.17–1.81 comparing BMI≥30kg/m2 to BMI between 21–22.9kg/m2).
Pancreatic cancer risk was stronger among individuals who were overweight in early adulthood (BMI≥25kg/m2) and obese at baseline (BMI≥30kg/m2) compared to individuals with a BMI<25kg/m2 in early adulthood and BMI<30kg/m2 at baseline (pooled MVRR=1.54, 95%CI=1.24–1.93) (). Results were stronger when the analysis was limited to never smokers (pooled MVRR=1.93, 95%CI=1.31–2.85). When we categorized the absolute difference of BMI at baseline and BMI at younger ages, we observed positive associations among individuals who had lost 2kg/m2 (MVRR=1.44, 95% CI=1.13–1.85), and gained ≥10kg/m2 (MVRR=1.40, 95%CI=1.13–1.72), but no statistically significant associations for those who gained 2-≤;5kg/m2 or 5-≤10kg/m2, compared to individuals whose BMI remained stable (BMI +/− 2kg/m2). To examine whether preclinical disease was related to the higher pancreatic cancer risk in those individuals who had lost 2kg/m2 from early adulthood to baseline, we excluded the first two years and the first five years from follow-up; the estimates were similar to the overall results (pooled multivariate RR removing 1st 2 years of follow-up = 1.47, 95% CI=1.14–1.89; pooled multivariate RR removing 1st 5 years of follow-up = 1.56, 95% CI=0.94–2.58).
No statistically significant associations with pancreatic cancer risk were observed for waist or hip circumference comparing the highest versus lowest quartile (). However, a 35% greater risk was observed among individuals in the highest versus lowest quartile of WHR (n = 6 studies; p-value, test for heterogeneity due to sex = 0.90). As we only have 3 studies contributing to the male and 4 studies contributing to the female specific estimates, we did not present the results for males and females, separately. However, the risk estimates, although not statistically significant, were similar to the overall (combined) results. Results were similar when we additionally adjusted for BMI at baseline.
Pooled Multivariate-Adjusted Relative Risks1 and 95% Confidence Intervals for Pancreatic Cancer According to Waist Circumference, Hip Circumference, and WHR
Height was not associated with pancreatic cancer risk overall () or among non-diabetics or never smokers. The nonparametric regression analyses showed that the association between height and pancreatic cancer risk was consistent with a linear (p-value, test for non-linearity>0.10), but null, association for men (pooled MVRR=1.02, 95%CI=0.97–1.06) and women (pooled MVRR=1.00, 95%CI=0.95–1.06) for an increment of 0.05m of height. Further, no association was observed when the outcome was limited to adenocarcinomas of the pancreas (data not shown).
Pooled Multivariate-Adjusted Relative Risks1–2 and 95% Confidence Intervals for Pancreatic Cancer According to Height
Overall, the associations of BMI at baseline(), BMI in early adulthood(), and height (data not shown) with pancreatic cancer risk were not modified by lifestyle and cohort characteristics. Although the interactions were not statistically significant, the positive associations for BMI at baseline and in early adulthood appeared stronger in never and past smokers than among current smokers. The association between BMI at baseline and pancreatic cancer risk varied by physical activity level; a slightly stronger positive association was observed in the high physical activity group (p-value, test for interaction=0.02). In addition, results for BMI at baseline, BMI in early adulthood and height were similar when we compared results from analyses limited to the first five years of follow-up with those of five or more years of follow-up, excluded cases diagnosed during the first two years of follow-up (data not shown), or stratified by the median age at diagnosis of the cases ().
Pooled Multivariate Relative Risks1 and 95% Confidence Intervals for Body Mass Index by Levels of Other Pancreatic Cancer Risk Factors
Using an aggregated dataset and controlling for study-specific differences in age at diagnosis, we explored differences in mean age at diagnosis of pancreatic cancer continuously and by categories of BMI in early adulthood and BMI at age of enrollment (baseline). When examining BMI at age of enrollment as a continuous variable, mean age of diagnosis of pancreatic cancer was significantly decreased by 0.11 years for each 1kg/m2 unit increase in BMI. In the categorical analysis, the mean age of diagnosis of pancreatic cancer was decreased by 3.38 years when comparing ≥30kg/m2 to <21kg/m2. Similarly, after adjusting for BMI at age at enrollment, mean age of diagnosis of pancreatic cancer was decreased significantly by 0.09 years for each 1kg/m2 unit increase in BMI at early adulthood, and 2.44 years when comparing ≥25 kg/m2 to <18.5kg/m2.