Should we consider gallbladder cancer a new smoking‐related cancer? A comprehensive meta‐analysis focused on dose–response relationships

Abstract

The few studies on the association of smoking with gallbladder cancer risk have given conflicting results. Here, we provide the most accurate and up-to-date quantification of the effect of cigarette smoking on gallbladder cancer risk, and investigate for the first time the dose-response relationships. Using an innovative approach for the identification of publications, we conducted a systematic review and meta-analysis of epidemiological studies published until March 2019 on the association of smoking with gallbladder cancer risk. Pooled relative risks (RRs) for smoking were estimated using random-effects models; one-stage randomeffects log-linear models were used for dose-response relationships. Out of 22 eligible articles, 20 (11 case-control and 9 cohort studies) were included in the meta-analysis, for a total of 4,676 gallbladder cancer cases. Compared to never smokers, the pooled RR was 1.33 (95% confidence interval [CI]: 1.17-1.51) for current and 1.07 (95% CI: 0.94-1.23) for former smokers. The risk of gallbladder cancer increased linearly with smoking intensity and duration, the RR being 1.60 (95% CI: 1.21-2.11) for 30 cigarettes/day and 1.25 (95% CI: 1.01-1.56) for 30 years of smoking. There was a nonsignificant linear decrease in gallbladder cancer risk with increasing time since quitting, compared to current smokers. Former smokers reached the risk of those who had never smoked 20 years after quitting. This comprehensive meta-analysis suggests a moderately but significantly higher risk of gallbladder cancer for current but not former smokers. We also provide the first report of a linear increase in gallbladder cancer risk according to smoking intensity and duration.Additional Supporting Information may be found in the online version of this article.

Risk factors for the onset of gallbladder cancer: a review

“…55 A recent meta-analysis found that smokers had a higher risk of GBC compared with nonsmokers (RR=1.33, 95% CI 1.17-1.51). 56 The risk of GBC was linearly correlated with smoking intensity and smoking duration, and the risk of GBC in smokers after quitting smoking did not decrease significantly with increasing smoking cessation time. Certainly, further work is needed to elaborate the relationship between smoking and alcohol consumption and the risk of GBC.…”

Cancer Prevention Strategies for Nepal

“…4 Of these major cancers listed in tables 1 and 2, while the role of tobacco smoking in lung and head and neck cancers is well-known, the documented contributions of this exposure to increased risks for cancers of the stomach, cervix, breast, ovary, and gallbladder are less highlighted and discussed. [5][6][7][8][9][10] The trends are for decreasing smoking in the last decade (7-11%), but markedly so for women, so part of the lung and other cancer story in women can be from previously much higher rates of smoking. 11,12 The smoking problem is compounded by the preponderance of data indicating that passive smoking-exposure to second-hand smoke-is associated with increased risk of lung and breast cancers.…”

Comments on “Should we consider gallbladder cancer a new smoking‐related cancer? A comprehensive meta‐analysis focused on dose‐response relationships”

“…1 Given the unsuitability of a randomized control trial to answer this question, we must rely on observational evidence. We therefore read with great interest the recent meta-analysis of cigarette smoking and gallbladder cancer risk by Lugo et al 2 This meta-analysis included case-control and cohort studies that provided risk or mortality estimates for either gallbladder cancer alone or biliary tract cancers and gallbladder cancer combined. Lugo et al found that cigarette smoking was positively associated with gallbladder cancer, with a pooled risk for current vs. never smoking across two casecontrol and eight cohort studies of 1.33 (95% CI: 1.17-1.51).…”

“…The relationship between cigarette smoking and gallbladder cancer risk could be modified by geographical factors.In the analysis by Lugo et al, there was evidence of effect modification by geography. In particular, higher pooled relative risks (RR) for the effect of ever vs never cigarette smoking on gallbladder cancer risk were observed in Asia (RR: 1.43) and North America (RR: 1.52), while the relative risks in Europe (RR: 1.16) and Oceania (RR: 1.00) were modest or null 2. It is plausible that the effect of cigarette smoking on gallbladder cancer risk may differ in the context of other risk factors that are geographically heterogeneous.…”

“…For example, pancreaticobiliary maljunction and congenital choledochal cysts are more prevalent in Asians than in Europeans,9 and the effect of smoking on gallbladder cancer risk could be amplified in this setting. Our pooled analysis was predominantly composed of studies conducted in North America and Europe (21 out of 26 studies in total),3 while the studies included in the analysis by Lugo et al were predominantly conducted in Asia (7 out of 10 studies in the current vs never smoking analysis) 2. Thus, geographic heterogeneity may represent another possible explanation for differing magnitudes of effects in these two analyses.#3.…”