Insulin, glucose and hepatocellular carcinoma risk in male hepatitis B carriers: results from 17-year follow-up of a population-based cohort

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http://carcin.oxfordjournals.org/content/32/6/876.abstract

Carcinogenesis

Volume32, Issue6

Pp. 876-881

Insulin, glucose and hepatocellular carcinoma risk in male hepatitis B carriers:

results from 17-year follow-up of a population-based cohort

Li-Ting Chao,

Chih-Feng Wu,

Feng-Yu Sung,

Chih-Lin Lin1,

Chun-Jen Liu2,

Chi-Jung Huang,

Keh-Sung Tsai3 and

Ming-Whei Yu*

+ Author Affiliations

Graduate Institute of Epidemiology and Preventive Medicine, College of Public

Health, National Taiwan University, Taipei, Taiwan

1Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei,

Taiwan

2Division of Gastroenterology, Department of Internal Medicine

3Department of Laboratory Medicine, National Taiwan University Hospital and

National Taiwan University College of Medicine, Taipei, Taiwan

*↵To whom correspondence should be addressed. Graduate Institute of

Epidemiology and Preventive Medicine, College of Public Health, National Taiwan

University, Room 522 No.17, Xuzhou Road Zhongzheng District, Taipei City 10055,

Taiwan. Fax: +886 2 23511955;Email: yumw@...

Received November 23, 2010.

Revision received January 29, 2011.

Accepted March 25, 2011.

Abstract

This study aimed to investigate the association of fasting insulin and glucose

levels with hepatocellular carcinoma (HCC) risk in a case–cohort study within

a cohort (1989–2006) of 2903 male government employees chronically infected

with hepatitis B virus (HBV) in Taiwan. Insulin, glucose and HBV-related factors

were assayed in baseline plasma among 124 HCC cases and a random subcohort of

1084 of the total cohort. After adjustment for demographics and HBV-related

factors, including viral load and genotype, the HCC risk was higher for the

highest [>6.10 μU/ml, hazard ratio (HR) = 2.36, 95% confidence interval (CI):

1.43–3.90] and lowest (<2.75 μU/ml, HR = 1.57, 95% CI: 0.96–2.58)

categories of insulin, compared with insulin of 2.75–4.10 μU/ml. The

dose–response relationship between insulin and HCC varied by follow-up time,

with stronger association for the HCC cases that occurred ≥8 years after

baseline (P for trend <0.0001). The effect of higher insulin on HCC risk

remained after adjustment for other metabolic factors, and was fairly consistent

across strata of age, body mass index, and HBV genotypic variants. However, it

was more profound among those with viral load <4.39 log10 copies/ml at

recruitment (>6.10 μU/ml, HR = 6.15, 95% CI: 2.48–15.22). Higher insulin was

also associated with an increased risk for cirrhosis diagnosed by

ultrasonography and elevated alanine aminotransferase. No association with

either cirrhosis or HCC was noted for glucose or diabetes after adjusting for

insulin. In conclusion, elevated insulin levels are an independent risk factor

for HCC among HBV carriers, especially for those with lower viral load.