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Threshold dose–response association between smoking pack-years and the risk of gallbladder cancer: A nationwide cohort study

  • Joo-Hyun Park
    Affiliations
    Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea

    Department of Healthcare Administration and Policy, School of Public Health, University of Nevada Las Vegas, USA
    Search for articles by this author
  • Jung Yong Hong
    Correspondence
    Corresponding author: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. Fax: +82 2 3412 3996.
    Affiliations
    Department of Healthcare Administration and Policy, School of Public Health, University of Nevada Las Vegas, USA

    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Kyungdo Han
    Affiliations
    Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
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Published:December 31, 2022DOI:https://doi.org/10.1016/j.ejca.2022.11.031

      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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