Highlights
- •Smoking ≥20 pack-years increased gallbladder cancer (GBC) risk.
- •A threshold dose–response was associated with smoking pack-years and GBC risk.
- •Smoking ≥20 pack-years and hyperglycaemia had a synergistic effect on GBC risk.
- •Smoking may be a modifiable risk factor for GBC.
- •More individualised cancer prevention education is required to reduce GBC risks.
Abstract
Background and aims
The association between smoking and gallbladder cancer (GBC) risk is unclear. We investigated
the association between smoking (including pack-years) and GBC risk. We also examined
the combined effects of smoking and diabetes or prediabetes on GBC risk.
Methods
This Korean nationwide cohort study included 9,520,629 adults without cancer who underwent
national health screening in 2009 and were followed-up until 2018. Multivariable Cox
proportional hazards models were used to determine risk estimates after adjusting
for potential confounders.
Results
During 78.4 million person-years (mean 8.2 ± 0.9 years) of follow-up, we identified
6066 patients with newly diagnosed GBC. Current and former smokers were associated
with increased GBC risk (hazard ratio [HR], 95% confidence interval [CI]: 1.117, 1.029–1.212
and 1.105, 1.016–1.202, respectively). Smoking of 20 to <30 and ≥30 pack-years was
independently associated with increased GBC risk compared with never smoking (HR,
95% CI; 1.241, 1.100–1.400 and 1.231, 1.107–1.370, respectively). However, smoking
of <10 and 10 to <20 pack-years was not. This threshold dose–response association
between smoking pack-years and GBC risk was observed regardless of the glycaemic status
(all P < 0.01). Furthermore, smoking of ≥20 pack-years and hyperglycaemia had a synergistic
effect on the GBC risk (all P < 0.01). Smokers with ≥20 pack-years with diabetes had the highest risk of GBC compared
to never smokers with normoglycaemia (HR, 1.658; 95% CI, 1.437–1.914).
Conclusions
Smoking was associated with increased GBC risk with a threshold dose–response effect
for smoking pack-years. The risk of GBC increases synergistically when smoking and
hyperglycaemia coexist. More individualised cancer prevention education is required
to reduce GBC risk.
Keywords
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Article info
Publication history
Published online: December 31, 2022
Accepted:
November 23,
2022
Received in revised form:
November 16,
2022
Received:
July 30,
2022
Identification
Copyright
© 2022 Published by Elsevier Ltd.
