Article

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

ABSTRACT

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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    • "In apparent contrast with our results for a-tocopherol and b-carotene supplementation, micronutrient status, as assessed by serum levels, has been associated with lower risk of liver cancer in several prospective cohort studies (Knekt et al, 1991; Yu et al, 1995; Ito et al, 2006; Yuan et al, 2006), including in the current one (companion paper). Within ATBC, we observed that higher baseline levels of serum b-carotene and retinol were associated with a reduced risk of incident liver cancer and CLD mortality, whereas higher baseline a-tocopherol levels were associated with a lower risk of CLD mortality but not incident liver cancer. "
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    ABSTRACT: Background: Recent data suggest the possible benefits of α-tocopherol and β-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. Methods: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) β-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. Results: Supplemental α-tocopherol, β-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. Conclusions: Long-term supplemental α-tocopherol or β-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.
    Full-text · Article · Oct 2014 · British Journal of Cancer
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    • "For example, retinol is a key regulator of transcription (Das et al, 2014). However, only a few human studies have examined the association of serum micronutrients with liver cancer or chronic liver disease, and most were conducted in Asia where HBV, one of the strongest risk factors for liver cancer and liver disease, is endemic (Knekt et al, 1991; Yu et al, 1995; Ito et al, 2006; Yuan et al, 2006). Therefore, we evaluated the association of serum a-tocopherol (a form of vitamin E), b-carotene, and retinol with incident liver cancer and CLD mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a prospective cohort of Finnish male smokers. "
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    ABSTRACT: Background: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. Methods: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. Results: Higher β-carotene and retinol levels were associated with less liver cancer (β-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (β-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of β-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. Conclusions: Our findings suggest that higher concentrations of β-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.
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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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    ABSTRACT: Despite several studies support a positive association between heavy alcohol consumption and liver cancer risk, a consistent dose-risk relationship has not yet been established. We carried out a systematic review and a meta-analysis of the association between alcohol intake and liver cancer occurrence, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. We searched for cohort and nested case-control studies on the general population published before April 2013, using PubMed and EMBASE. Summary meta-analytic relative risks (RRs) were estimated using random-effect models. We included 16 articles (19 cohorts) for a total of 4445 incident cases and 5550 deaths from liver cancer. Compared with non-drinking, the pooled RRs were 0.91 (95% confidence interval, CI, 0.81-1.02) for moderate drinking (<3 drinks per day) and 1.16 (95% CI, 1.01-1.34) for heavy drinking (≥3 drinks per day), with significant heterogeneity among studies. The dose-risk curve suggested a linear relationship with increasing alcohol intake in drinkers, with estimated excess risk of 46% for 50 g of ethanol per day and 66% for 100 g per day. This systematic review suggests a moderate detrimental role of consumption of 3 or more alcoholic drinks per day on liver cancer, and a lack of association with moderate drinking. Our results have to be taken with due caution on account of the possible limitations of the original studies included in the meta-analysis.
    Full-text · Article · Mar 2014 · Annals of Oncology
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