Non-linear dose-response relationship between cigarette smoking and pancreatic cancer risk: evidence from a meta-analysis of 42 observational studies

Background: Question remains about the shape of the dose-response relationship between cigarette smoking and pancreatic cancer risk.

Methods: Relevant studies were identified by searching PubMed, ISI Web of Science and China National Knowledge Infrastructure (CNKI) databases and by reviewing the reference lists of retrieved articles. Random-effects models were applied to estimate summary relative risks (RRs).

Results: Forty-two publications were finally included. The overall meta-analysis showed evidence of non-linear association between smoking intensity and pancreatic cancer risk (P for non-linearity=0.000). Compared with non-smokers, the summary RRs were 1.5 (95% confidence interval (CI): 1.4, 1.6) for 10 cigarettes/day, 1.9 (95% CI: 1.8, 2.0) for 20 cigarettes/day, 2.0 (95% CI: 1.9, 2.1) for 30 cigarettes/day and 2.1 (95% CI: 1.9, 2.3) for 40 cigarettes/day with marginal between-study heterogeneity (I(2)=29%). Similar results were also found for smoking duration and cumulative amount of cigarettes smoked. Besides, the summary RR for former smokers reduced with increasing time since quitting smoking compared with current smokers without heterogeneity (P for non-linearity=0.008, I(2)=0%). The results of stratified analysis by study design were comparable to those of overall meta-analysis. When stratified by sex, non-linear dose-response associations were detected for all metrics of cigarette smoking in women, while linear relationships were observed for smoking duration and cumulative amount of cigarettes smoked in men except for smoking intensity.

Conclusion: This meta-analysis reveals a non-linear dose-response association between cigarette smoking and pancreatic cancer risk, but it might differ between sexes.