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Relationship of Insulin-Like Growth Factors System Gene Polymorphisms with the Susceptibility and Pathological Development of Hepatocellular Carcinoma

  • Hepatobiliary Tumors
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Abstract

Background

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. The insulin-like growth factors (IGFs) system consists of a group of proteins which may induce cell proliferation and inhibit cell apoptosis through several signal pathways, leading to transformation of normal cells into cancer cells. However, the impact of genetic polymorphisms of the IGFs system on HCC has not been clarified.

Methods

In this case–control study, a total of 102 HCC patients and 306 age- and gender-matched controls were recruited. The genetic polymorphisms of the IGFs system genes, including IGF-1, IGF-2, IGF-1receptor (IGF-1R), IGF-2R, IGF binding protein (IGFBP-3), and insulin (INS) genes, were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and real-time PCR genotyping analysis.

Results

A significant difference (p = 0.02) between case and control group in the distribution frequency of IGF-2 +3580 polymorphism was observed. Multiple regression model analysis showed that the presence of AA or AG at IGF-2R may exhibit a potential protective effect against hepatitis C [odds ratio (OR) = 0.35, 95% confidence interval (CI) = 0.15–0.82]. The combination of IGF-2 +3580 AA genotype and IGF-2R GG genotype may present a significantly lower risk of HCC (OR = 0.20, 95% CI = 0.05–0.87). Additionally, no polymorphisms of any IGFs system genes were associated with liver-related clinicopathological markers in serum.

Conclusions

Among IGFs system genes, IGF-2 and IGF-2R gene polymorphisms and combination could be considered as the most important factors contributing to increased susceptibility and pathological development of HCC.

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Acknowledgment

This study was supported by a research Grant from National Science Council, Taiwan (NSC97-2314-B-040-025-MY3).

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Authors and Affiliations

  1. Graduate Institute of Applied Science of Living, Tainan University of Technology, Tainan, Taiwan

    Chia-Jui Weng PhD

  2. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Yi-Hsien Hsieh PhD

  3. Chest Hospital, Department of Health, Executive Yuan, Tainan, Taiwan

    Chiung-Man Tsai MS

  4. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Yin-Hung Chu MS, Kwo-Chang Ueng PhD, Yuan-Hung Yeh MD, Mu-Kuan Chen MD, PhD & Shun-Fa Yang PhD

  5. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

    Kwo-Chang Ueng PhD

  6. Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan

    Yu-Fan Liu PhD

  7. Yang-Ming Rehabilitation Clinic, Taichung, Taiwan

    Yuan-Hung Yeh MD

  8. Department of Molecular and Cellular Medicine, Texas A&M University System Health Science Center, College Station, TX, USA

    Shih-Chi Su MS

  9. School of Nutrition, Chung Shan Medical University, Taichung, Taiwan

    Yi-Chen Chen PhD

  10. Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

    Mu-Kuan Chen MD, PhD

  11. Mingdao University, Changhua, Taiwan

    Mu-Kuan Chen MD, PhD

  12. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

    Shun-Fa Yang PhD

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  1. Chia-Jui Weng PhD
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  2. Yi-Hsien Hsieh PhD
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Corresponding authors

Correspondence to Mu-Kuan Chen MD, PhD or Shun-Fa Yang PhD.

Additional information

Chia-Jui Weng and Yi-Hsien Hsieh contributed equally to this article.

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Weng, CJ., Hsieh, YH., Tsai, CM. et al. Relationship of Insulin-Like Growth Factors System Gene Polymorphisms with the Susceptibility and Pathological Development of Hepatocellular Carcinoma. Ann Surg Oncol 17, 1808–1815 (2010). https://doi.org/10.1245/s10434-009-0904-8

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  • DOI: https://doi.org/10.1245/s10434-009-0904-8

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