Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts

doi:10.1038/s41416-022-01877-5

. 2022 Oct;127(6):1069-1075.

doi: 10.1038/s41416-022-01877-5. Epub 2022 Jun 17.

Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts

Xiao Luo^{1

2}, Wanshui Yang^{3

4}, Amit D Joshi³, Kana Wu¹, Tracey G Simon^{5

6

7}, Chen Yuan⁸, Lina Jin^{3

9}, Lu Long^{3

10}, Mi Na Kim^{11

12}, Chun-Han Lo^{6

7}, Xing Liu^{1

13}, Thomas A Abrams¹⁴, Brian M Wolpin⁸, Andrew T Chan^{3

6

7}, Edward L Giovannucci^{1

3

15}, Xuehong Zhang^{16

17}

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
² Department of Health Statistics, School of Public Health, China Medical University, Shenyang, Liaoning, P. R. China.
³ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ School of Public Health, Anhui Medical University, Hefei, Anhui, P. R. China.
⁵ Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁹ Department of Epidemiology and Biostatistics, Jilin University School of Public Health, Changchun, Jilin, P. R. China.
¹⁰ Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, P. R. China.
¹¹ Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
¹² Laboratory of Clinical Epidemiology in Hepatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
¹³ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, P. R. China.
¹⁴ Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁶ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. xuehong.zhang@channing.harvard.edu.
¹⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. xuehong.zhang@channing.harvard.edu.

PMID: 35715632
PMCID: PMC9470543
DOI: 10.1038/s41416-022-01877-5

Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts

Xiao Luo et al. Br J Cancer. 2022 Oct.

. 2022 Oct;127(6):1069-1075.

doi: 10.1038/s41416-022-01877-5. Epub 2022 Jun 17.

Authors

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
² Department of Health Statistics, School of Public Health, China Medical University, Shenyang, Liaoning, P. R. China.
³ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ School of Public Health, Anhui Medical University, Hefei, Anhui, P. R. China.
⁵ Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁹ Department of Epidemiology and Biostatistics, Jilin University School of Public Health, Changchun, Jilin, P. R. China.
¹⁰ Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, P. R. China.
¹¹ Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
¹² Laboratory of Clinical Epidemiology in Hepatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
¹³ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, P. R. China.
¹⁴ Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁶ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. xuehong.zhang@channing.harvard.edu.
¹⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. xuehong.zhang@channing.harvard.edu.

PMID: 35715632
PMCID: PMC9470543
DOI: 10.1038/s41416-022-01877-5

Abstract

Background: Gallstones may result in inflammation, altered bile flow, and changes in metabolic hormone levels, thereby increasing cancer risk. However, previous studies for gallstones and cancers of the liver, biliary tract and pancreas in the U.S. were relatively limited.

Methods: We followed 115,036 women from the Nurses' Health Study (1982-2012) and 49,729 men from the Health Professionals Follow-up Study (1986-2012). History of gallstones, including with or without performed cholecystectomy, was reported at baseline and updated through biennial questionnaires. The Cox proportional hazard regression model was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results: During up to 30-year follow-up, we identified 204 incidents of liver cancer, 225 biliary tract cancer and 1147 pancreatic cancer cases. Compared to those without gallstones diagnosis, the multivariable HRs for individuals with gallstones (untreated or with cholecystectomy) were 1.60 for liver cancer (95% CI: 1.14-2.26), 4.79 for biliary tract cancer (95% CI: 3.02-7.58), and 1.13 for pancreatic cancer (95% CI: 0.96-1.32). The multivariable HRs for individuals with cholecystectomy were 1.33 for liver cancer (95% CI: 0.90-1.95) and 1.15 for pancreatic cancer (95% CI: 0.98-1.36).

Conclusions: Gallstones were associated with a higher risk of cancers of the liver, biliary tract and possibly pancreas.

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Conflict of interest statement

The authors declare no competing interests.

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References

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[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2018;68:394–424. - PubMed

[2] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2018;68:394–424. - PubMed

[3] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: A Cancer J Clin. 2019;69:7–34. - PubMed

[4] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: A Cancer J Clin. 2019;69:7–34. - PubMed

[5] Petrick JL, Braunlin M, Laversanne M, Valery PC, Bray F, McGlynn KA. International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007. Int J Cancer. 2016;139:1534–45. doi: 10.1002/ijc.30211. - DOI - PMC - PubMed

[6] Petrick JL, Braunlin M, Laversanne M, Valery PC, Bray F, McGlynn KA. International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007. Int J Cancer. 2016;139:1534–45. doi: 10.1002/ijc.30211. - DOI - PMC - PubMed

[7] Luo G, Zhang Y, Guo P, Ji H, Xiao Y, Li K. Global patterns and trends in pancreatic cancer incidence: age, period, and birth cohort analysis. Pancreas. 2019;48:199–208. doi: 10.1097/MPA.0000000000001230. - DOI - PubMed

[8] Luo G, Zhang Y, Guo P, Ji H, Xiao Y, Li K. Global patterns and trends in pancreatic cancer incidence: age, period, and birth cohort analysis. Pancreas. 2019;48:199–208. doi: 10.1097/MPA.0000000000001230. - DOI - PubMed

[9] Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21. doi: 10.1158/0008-5472.CAN-14-0155. - DOI - PubMed

[10] Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21. doi: 10.1158/0008-5472.CAN-14-0155. - DOI - PubMed

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Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts

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Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts

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