Prediagnostic Level of Serum Retinol in Relation to Reduced Risk of Hepatocellular Carcinoma

The Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 04/2006; 98(7):482-90. DOI: 10.1093/jnci/djj104
Source: PubMed


Retinol and its derivatives (retinoids), which have antioxidant activity and promote cell differentiation, may protect against the development of hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and reducing inflammatory responses.
We examined prospectively the relationship between prediagnostic serum concentrations of retinol, alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; and selenium and the risk of developing HCC among 213 patients with HCC and 1087 matched control subjects from a cohort of 18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum concentrations of micronutrients were estimated by using logistic regression with adjustment for cigarette smoking status, alcohol intake, self-reported history of physician-diagnosed hepatitis or liver cirrhosis at recruitment, and seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests were two-sided.
Men with high prediagnostic serum retinol levels had a lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95% CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant interaction was observed between retinol and HBsAg seropositivity on HCC risk; HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in the highest tertile of retinol (Pinteraction = .018). No independent effect of serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC risk were observed.
High prediagnostic serum level of retinol is associated with a decreased risk of HCC in this population.

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    • "CIs were calculated from the SEs of the crude ORs penalized by 1.5, using the distribution of cases and controls across exposure categories Yuan et al. 2006 [29] China 213 M 1087 M 1986/1989–2001 (15 years) Date of birth, date of blood collection, residence, serum level of retinol Nested case–control study based on a cohort of 18 244 men followed up in the Shanghai Cohort Study 11.6% of the controls had history of hepatitis or liver cirrhosis; 9.6% were HBsAg+; 0.2% were HCVAb+ Ohishi et al. 2008 [30] "
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    • "It induces cellular differentiation of numerous malignant tumors and inhibits their growth (13). Notably, epidemiological evidence indicates that low levels of serum retinol are correlated with HCC risk (14,15), suggesting a potential role of retinoids in the chemoprevention of this cancer. Consistent with this view, in vitro and in vivo preclinical evidence indicated that ATRA was able to inhibit proliferation and induce apoptosis in human hepatoma cells (Hep3B) (16) and suppressed tumorigenicity in a nude mouse model (17). "
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    • "In fact, in a population-based 11.7-year follow-up study on mortality rates from cancer in a Japanese population, higher serum tocopherol (vitamin E) levels did not correlate with reduced risk of mortality from liver cancer [108]. Moreover, in a 15-year follow-up prospective study in males, high serum levels of tocopherols did not reduce the risk of developing HCC [109]. One epidemiological study has examined the role of dietary vitamin C in liver cancer etiology. "
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