Journal of the National Cancer Institute Advance Access originally published online on August 8, 2007
JNCI Journal of the National Cancer Institute 2007 99(16):1240-1247; doi:10.1093/jnci/djm084
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Published by Oxford University Press 2007.
ARTICLES |
Chemoprevention of Primary Liver Cancer: A Randomized, Double-Blind Trial in Linxian, China
Affiliations of authors: Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China (CXQ, JHF, XDS, YLQ); Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (FK, PRT, BEC, CCA, SMD); Information Management Services, Silver Spring, MD (BY); Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, CO (SDM)
Correspondence to: Farin Kamangar, MD, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rm 3034, Bethesda, MD 10892-7232 (e-mail: kamangaf{at}mail.nih.gov) or You-Lin Qiao, MD, PhD, Department of Cancer Epidemiology, Cancer Institute, Chinese Academy of Medical Sciences, PO Box 2258, Beijing 100021, People’s Republic of China (e-mail: qiaoy{at}public.bta.net.cn).
Background: Primary liver cancer is a common malignancy with a dismal prognosis. New primary prevention strategies are needed to reduce mortality from this disease. We examined the effects of supplementation with four different combinations of vitamins and minerals on primary liver cancer mortality among 29450 initially healthy adults from Linxian, China.
Methods: Participants were randomly assigned to take either a vitamin–mineral combination ("factor") or a placebo daily for 5.25 years (March 1986–May 1991). Four factors (at doses one to two times the US Recommended Daily Allowance)—retinol and zinc (factor A); riboflavin and niacin (factor B); ascorbic acid and molybdenum (factor C); and beta-carotene, alpha-tocopherol, and selenium (factor D)—were tested in a partial factorial design. The study outcome was primary liver cancer death occurring from 1986 through 2001. Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of liver cancer death with and without each factor. All P values are two-sided.
Results: A total of 151 liver cancer deaths occurred during the analysis period. No statistically significant differences in liver cancer mortality were found comparing the presence and absence of any of the four intervention factors. However, both factor A and factor B reduced liver cancer mortality in individuals younger than 55 years at randomization (HR = 0.59, 95% CI = 0.34 to 1.00, and HR = 0.54, 95% CI = 0.31 to 0.93, respectively) but not in older individuals (HR = 1.06, 95% CI = 0.71 to 1.59, and HR = 1.12, 95% CI = 0.75 to 1.68, respectively). Factor C reduced liver cancer death, albeit with only borderline statistical significance in males (HR = 0.70, 95% CI = 0.47 to 1.02) but not in females (HR = 1.30, 95% CI = 0.72 to 2.37). Cumulative risks of liver cancer death were 6.0 per 1000 in the placebo arm, 5.4 per 1000 in the arms with two factors, and 2.4 per 1000 in the arm with all four factors.
Conclusion: None of the factors tested reduced overall liver cancer mortality. However, three factors reduced liver cancer mortality in certain subgroups.
| CONTEXT AND CAVEATS Prior knowledge Liver cancer is relatively common, and the death rate from the disease is high. Several possible chemoprevention strategies are being investigated, including nutritional chemoprevention. Study design The Linxian General Population Trial was a randomized factorial intervention trial that examined the effects of four vitamin–mineral combinations ("factors"), taken for 5.25 years, on incidence of and mortality from several cancers in a Chinese population with inadequate intake of multiple vitamins and minerals. Follow-up (an average of nearly 13 years) is now sufficient to examine liver cancer mortality. Contribution None of the factors reduced mortality from liver cancer overall. However, some factors reduced liver cancer mortality in subgroups defined by age or sex. Implications In populations with poor nutrition, certain subgroups may experience reduced liver cancer mortality if they take certain nutritional supplements. Limitations Some of the results, including the subgroup findings, may have arisen by chance. Because each intervention factor was a combination of several vitamins and minerals, it was not possible to evaluate the independent effect of each vitamin or mineral. The population of Linxian may not be representative of other populations, especially vitamin-replete populations.
|
Manuscript received November 27, 2006; revised June 6, 2007; accepted June 27, 2007.
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 1213.