Association between Lipid Profiles and the Incidence of Hepatocellular Carcinoma: A Nationwide Population-Based Study

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Abstract

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Cholesterol plays an important role in cell structure and cell proliferation. Altered lipid metabolism have been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development using large-scale, nationally representative data from the Korean National Health Insurance Service. During a median of 7.3 years follow-up, 26,891 incident HCCs were identified. The incidence of HCC gradually decreased according to the increase of total-cholesterol and LDL-cholesterol. This inverse association was consistent across subgroups stratified by the presence of liver cirrhosis or viral hepatitis. This large nationwide population-based study suggests that low lipid profile is an independent risk factor and preclinical marker for HCC.

Abstract

Background and Aims: Altered lipid metabolism has been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development. Methods: Data were obtained from the Korean National Health Insurance Service from 2009 to 2017. Cox regression analysis was used to examine the hazard ratios of HCC in 8,528,790 individuals who had undergone health check-ups in 2009. Results: During a median of 7.3 years follow-up, 26,891 incidents of HCCs were identified. The incidence of HCC (per 100,000 person-years) gradually decreased according to the increase in total-cholesterol and LDL-cholesterol; the incidence of HCC was 69.2, 44.0, 33.9, and 25.8 in quartile-1 (Q1), Q2, Q3, and Q4 population of total-cholesterol, and 63.6, 44.5, 37.2, and 28.3 in Q1, Q2, Q3, and Q4 population of LDL-cholesterol, respectively. Compared to Q1 of total-cholesterol, subjects in higher total-cholesterol levels were associated with a lower incidence of HCC (multiple covariates-adjusted hazard ratio (aHR): Q2 0.61; Q3 0.46; Q4 0.36). These associations were consistently observed in stratified subgroup analysis by the presence of liver cirrhosis or viral hepatitis. Conclusions: Low serum lipid levels were significantly associated with the increased risk of developing HCC. A low lipid profile might be an independent risk factor and preclinical marker for HCC.

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Most cited references 30

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Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development

Franziska Baenke, Barrie Peck, Heike Miess … (2013)

An increased rate of lipid synthesis in cancerous tissues has long been recognised as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids to cellular transformation, tumour development and tumour progression, as well as their potential role in facilitating the spread of cancerous cells to secondary sites, are not yet fully understood. In this article, we review the recent findings that support the importance of lipid synthesis and metabolism in tumorigenesis. Specifically, we explore the role of aberrant lipid biosynthesis in cancer cell migration and invasion, and in the induction of tumour angiogenesis. These processes are crucial for the dissemination of tumour cells and formation of metastases, which constitute the main cause of cancer mortality.

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Total cholesterol and cancer risk in a large prospective study in Korea.

Cari M. Kitahara, Amy Berrington de Gonzalez, Neal Freedman … (2011)

To further clarify the relationship between total cholesterol and cancer, which remains unclear. We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death. Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32). In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site.

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Lipid metabolism and carcinogenesis, cancer development.

Jia Long, Chan-Juan Zhang, Neng Zhu … (2018)

The disorder of lipid metabolism is pathologically linked to hyperlipidemia, lipid storage disease, obesity and other related diseases. Intriguingly, recent studies have revealed that lipid metabolism disorders play an important role in carcinogenesis and development as well, since they cause abnormal expression of various genes, proteins, and dysregulation of cytokines and signaling pathways. More importantly, lipid-lowering drugs and anti-lipid per-oxidation treatment have been showing their advantages in clinic, in comparison with other anti-cancer drugs with high toxicity. Thus, further elucidation of molecular mechanism between lipid metabolism and cancer is essential in developing novel diagnostic biomarkers and therapeutic targets of human cancers.

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Author and article information

Contributors

Masahito Shimizu: Role: Academic Editor

Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 30 March 2021

Publication date Collection: April 2021

Volume: 13

Issue: 7

Electronic Location Identifier: 1599

Affiliations

[1 ]Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea; yuricho@ 123456ncc.re.kr

[2 ]Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul 06135, Korea

[3 ]Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea; creatio3@ 123456snu.ac.kr

[4 ]Department of Gastroenterology and Hepatology, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Korea; puby17@ 123456naver.com

[5 ]Department of Gastroenterology and Hepatology, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea; chyoung@ 123456schmc.ac.kr

[6 ]Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul 06236, Korea; gohwom@ 123456snu.ac.kr

[7 ]Department of Family Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 07061, Korea; dpsme@ 123456snu.ac.kr

[8 ]Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA

[9 ]Department of Biostatistics, College of Medicine, The Soongsil University, Seoul 06978, Korea; ujk8774@ 123456catholic.ac.kr (S.-H.P.); hkd@ 123456ssu.ac.kr (K.H.)

[10 ]Department of Family Medicine, Samsung Medical Center Supportive Care Center, Samsung Comprehensive Cancer Center, Seoul 06351, Korea

[11 ]Department of Digital Health, SAIHST, Sungkyunkwan University; 81 Irwon-Ro Gangnam-gu, Seoul 06351, Korea

Author notes

[* ]Correspondence: dwshin@ 123456skku.edu (D.W.S.); ydoctor2@ 123456snu.ac.kr (S.J.Y.); Tel.: +82-2-3410-0200 (D.W.S); +82-2-2072-2228 (S.J.Y.); Fax: +82-2-3410-0231 (D.W.S.); +82-2-743-6701 (S.J.Y.)

[†]

These two authors contributed equally to this work.

Author information

Yuri Cho https://orcid.org/0000-0002-4488-5352

Eun Ju Cho https://orcid.org/0000-0002-2677-3189

Jeong-Ju Yoo https://orcid.org/0000-0002-7802-0381

Article

Publisher ID: cancers-13-01599

DOI: 10.3390/cancers13071599

PMC ID: 8037932

PubMed ID: 33808412

SO-VID: 2b16e393-e67b-4091-b8b6-5cd87bebb52d

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Association between Lipid Profiles and the Incidence of Hepatocellular Carcinoma: A Nationwide Population-Based Study

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Karger: Oncology

Most cited references 30

Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development

Total cholesterol and cancer risk in a large prospective study in Korea.

Lipid metabolism and carcinogenesis, cancer development.

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