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Risk factors for hepatocellular carcinoma (HCC) in the northeast of the United States: results of a case–control study

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Abstract

Purpose

HCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case–control study in Connecticut, New Jersey and part of New York City.

Methods

Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors.

Results

The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2–204) and 2.13 (95% CI 1.52–3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10 years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls.

Conclusions

Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.

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Acknowledgments

The cooperation of 28 Connecticut hospitals, including Charlotte Hungerford Hospital, Bridgeport Hospital, Danbury Hospital, Hartford Hospital, Middlesex Hospital, New Britain General Hospital, Bradley Memorial Hospital, Yale/New Haven Hospital, St. Francis Hospital and Medical Center, St. Mary’s Hospital, Hospital of St. Raphael, St. Vincent’s Medical Center, Stamford Hospital, William W. Backus Hospital, Windham Hospital, Eastern Connecticut Health Network, Griffin Hospital, Bristol Hospital, Johnson Memorial Hospital, Day Kimball Hospital, Greenwich Hospital, Lawrence and Memorial Hospital, Milford Hospital, New Milford Hospital, Norwalk Hospital, MidState Medical Center, John Dempsey Hospital and Waterbury Hospital, in allowing patient access, is gratefully acknowledged. This study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in this study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. The New Jersey State Cancer Registry (NJSCR) was supported by the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) under the cooperate agreement 5NU58DP006279-02-00, the National Institute’s Surveillance, Epidemiology, and End Results (SEER) Program under contract number HHSN261201300021I, N01-PC-2013-00021, the State of New Jersey, and the Rutgers Cancer Institute. The authors especially thank Rajni Mehta for her support in case identification through RCA, Helen Sayward for her effort in conducting the study and Dr. Theresa Lukose for her effort in coordinating the study recruitment in the Transplant Clinical Research Center at Columbia University Medical Center. Funding was provided by National Cancer Institute (Grant Nos. R01CA138698 and U01CA230690).

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Authors and Affiliations

  1. Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA

    Yi Shen, Zhanwei Wang, Wei Jia, Linda Wong & Herbert Yu

  2. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA

    Harvey Risch, Lingeng Lu, Xiaomei Ma & Melinda L. Irwin

  3. Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

    Joseph K. Lim & Tamar Taddei

  4. New Jersey State Cancer Registry, New Jersey Department of Health, Trenton, NJ, USA

    Karen Pawlish

  5. Rutgers Cancer Institute, Rutgers School of Public Health, New Brunswick, NJ, USA

    Antoinette Stroup

  6. Department of Medicine, Weill Cornell Medical College, College of Physicians & Surgeons, Columbia University, New York, NY, USA

    Robert Brown

  7. Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD, USA

    Susan T. Mayne

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  1. Yi Shen
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  2. Harvey Risch
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  15. Herbert Yu
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Correspondence to Herbert Yu.

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10552_2020_1277_MOESM1_ESM.pdf

Supplemental Figure S1. Average BMI at ages 20s, 30s, 40s and 50s in HCC patients without HCV infection (top line), HCC patients with HCV infection (middle line) and population controls (bottom line) (PDF 34 kb)

Supplemental Figure S2. Median and mean ages of HCC patients grouped by HCV infection and obesity status (PDF 35 kb)

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Shen, Y., Risch, H., Lu, L. et al. Risk factors for hepatocellular carcinoma (HCC) in the northeast of the United States: results of a case–control study. Cancer Causes Control 31, 321–332 (2020). https://doi.org/10.1007/s10552-020-01277-1

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  • DOI: https://doi.org/10.1007/s10552-020-01277-1

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