title: Reduced aflatoxin exposure presages decline in liver cancer mortality in an endemic region of China.
abstract: Primary liver cancer (PLC) is the third leading cause of cancer mortality globally. In endemic areas of sub-Saharan Africa and Asia, PLC largely arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Although synergistic interactions between these two risk factors have been observed in cohort studies in China, here we determined the impact of agricultural reforms in the 1980s leading to diminished maize consumption and implementation of subsidized universal vaccination against HBV in the 2000s on PLC primary prevention. A population-based cancer registry was used to track PLC mortality in Qidong, China and was compared with the timeline of HBV immunization. Randomly selected serum samples from archived cohort collections from the 1980s to present were analyzed for aflatoxin biomarkers. More than 50% reductions in PLC mortality rates occurred across birth cohorts from the 1960s to the 1980s for Qidongese less than 35 years of age although all were born before universal vaccination of newborns. Median levels of the aflatoxin biomarker decreased from 19.3 pg/mg albumin in 1989 to undetectable (<0.5 pg/mg) by 2009. A population attributable benefit of 65% for reduced PLC mortality was estimated from a government-facilitated switch of dietary staple from maize to rice; 83% of this benefit was in those infected with HBV. Food policy reforms in China resulted in a dramatic decrease in aflatoxin exposure, which, independent of HBV vaccination, reduced liver cancer risk. The extensive HBV vaccine coverage now in place augurs even greater risk reductions in the future.
authors: Room E1352 BSTWR, University of Pittsburgh, Pittsburgh, PA 15261. tkensler@pitt.edu.
authors: Jian-Guo
authors: JG
authors: Chen
authors: Patricia A
authors: PA
authors: Egner
authors: Derek
authors: D
authors: Ng
authors: Lisa P
authors: LP
authors: Jacobson
authors: Alvaro
authors: A
authors: Muñoz
authors: Yuan-Rong
authors: YR
authors: Zhu
authors: Geng-Sun
authors: GS
authors: Qian
authors: Felicia
authors: F
authors: Wu
authors: Jian-Min
authors: JM
authors: Yuan
authors: John D
authors: JD
authors: Groopman
authors: Thomas W
authors: TW
authors: Kensler
mesh_terms: D000328:Adult; D000348:Aflatoxins / Q000633:toxicity*; D000368:Aged; D000418:Albumins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000401:mortality / Q000821:virology; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D004032:Diet; D019353:Endemic Diseases / Q000706:statistics & numerical data; D004781:Environmental Exposure; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000517:prevention & control; D017325:Hepatitis B Vaccines / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000401:mortality* / Q000821:virology; D008297:Male; D008875:Middle Aged; D018673:Nutrition Policy; D012275:Oryza; D012042:Registries; D012307:Risk Factors; D055815:Young Adult; D003313:Zea mays / Q000378:metabolism
chemical_list: D000348:Aflatoxins; D000418:Albumins; D015415:Biomarkers; D017325:Hepatitis B Vaccines
references: Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1436-9
references: 18559559
references: Carcinogenesis. 2010 Jan;31(1):71-82
references: 19875698
references: J Med Screen. 2003;10(4):204-9
references: 14738659
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2605-13
references: 16284385
references: Environ Health Perspect. 2005 Dec;113(12):1779-83
references: 16330363
references: Zhonghua Liu Xing Bing Xue Za Zhi. 2010 Jul;31(7):721-6
references: 21162830
references: Cancer Epidemiol Biomarkers Prev. 1997 Apr;6(4):257-65
references: 9107431
references: Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):3-10
references: 8118382
references: Cancer Res. 1989 May 1;49(9):2506-9
references: 2539905
references: IARC Sci Publ. 2011;(162):43-53
references: 21675405
references: Stat Med. 2007 Oct 15;26(23):4352-74
references: 17342754
references: Hepatology. 2002 Nov;36(5):1214-20
references: 12395332
references: Cancer Lett. 2009 Dec 1;286(1):5-8
references: 19070421
references: Sci Transl Med. 2012 Mar 28;4(127):127rv4
references: 22461645
references: Semin Cancer Biol. 2011 Feb;21(1):59-69
references: 21144900
references: J Natl Cancer Inst. 2009 Oct 7;101(19):1348-55
references: 19759364
references: Gastroenterology. 2012 May;142(6):1264-1273.e1
references: 22537432
references: Eur J Cancer. 2012 Sep;48(14):2125-36
references: 22405700
references: Cancer Prev Res (Phila). 2011 Mar;4(3):384-95
references: 21372038
references: Stat Med. 2005 Jul 15;24(13):2053-67
references: 15803450
references: Intervirology. 1995;38(3-4):155-61
references: 8682610
references: Sci Sin B. 1983 Nov;26(11):1166-75
references: 6422550
references: MMWR Morb Mortal Wkly Rep. 2007 May 11;56(18):441-5
references: 17495790
references: Carcinogenesis. 1996 Jun;17(6):1317-21
references: 8681449
references: J Cell Physiol Suppl. 1986;4:83-90
references: 3018008
references: Toxicol Sci. 2011 Mar;120 Suppl 1:S28-48
references: 20881231
references: Hepatology. 1996 Jul;24(1):38-42
references: 8707279