中国启东肝癌预防：黄曲霉毒素生物标志物研究的经验
Patricia A. Egner1, 王金兵2, 朱源荣2, Lisa P. Jacobson1, Derek Ng1, Alvaro Muñoz1, Jed W. Fahey1, 陈建国2, 陈陶阳2, 钱耕荪2, John D. Groopman1, Thomas W. Kensler*1,3
化学进展 ›› 2013, Vol. 25 ›› Issue (09) :1454-1461
中国启东肝癌预防：黄曲霉毒素生物标志物研究的经验
Prevention of Liver Cancer in Qidong, China：Lessons from Aflatoxin Biomarker Studies
原发性肝癌一直是中国启东癌症死亡的首要原因,这一地区的110 万居民中大约每年有800人死于原发性肝癌。流行病学研究已经强调了乙肝病毒感染和肝致癌物黄曲霉素的饮食暴露在启东和其他流行地区作为关键相互作用的风险决定因素的重要性。由于生物标志物的发展,使得在病例对照研究和其他群体研究中可以检测这些风险因素的流行程度。20 世纪80 年代曾经在启东进行了乙肝病毒疫苗接种试点,但直到本世纪初才在新生儿上普遍接种。尽管目前疫苗接种对癌症死亡率的影响微乎其微,但该项目旨在减缓这一地区未来几代人肝脏疾病包括肝癌的发展。减少对黄曲霉毒素暴露的策略也是必需的,尤其是对于那些已经感染乙肝病毒的人群。我们已经进行了一系列原理验证性的临床试验,包括使用药物、膳食补充剂和食物来改变不可避免的暴露后黄曲霉素的代谢及排出。使用黄曲霉素生物标志物作为中间指标,奥替普拉、叶绿素和西兰花豆芽饮料已被证明有效,突出了低成本化学预防途径在预防环境致癌中的作用。值得注意的是,最近对存档的血清样本的回顾性分析表明,启东的黄曲霉素暴露在过去的25 年里下降了40 倍,这可能是由从玉米到大米的主食变化带来的。因此,一级预防,伴随着20世纪80 年代经济和农业政策改变的作用,带来了出乎意料的在短时间内消除这个地区肝癌地方性流行的希望。
Primary liver cancer has been the leading cause of cancer death in Qidong, China, with about 800 deaths annually in this region of 1.1 million residents. Epidemiological studies have highlighted the importance of infection with hepatitis B virus (HBV) and dietary exposure to hepatocarcinogenic aflatoxins as key, interactive determinants of risk in Qidong and other endemic areas. Identification of these risk factors was enabled through the development of biomarkers allowing for measures of their prevalence in case-control and other study cohorts. Vaccination against HBV began in pilot studies in the 1980s in Qidong but did not become universal for newborns until earlier this decade. Despite minimal impact on cancer mortality to date, vaccination programs are poised to blunt the development of liver diseases including cancer in this region over the next generations. Strategies for reducing aflatoxin exposure are also required, especially for those already infected with HBV. We have conducted a series of proof-of-principle clinical trials in which drugs, dietary supplements and foods have been used to alter the metabolism and elimination of aflatoxins following unavoidable exposures. Using aflatoxin biomarkers as intermediate endpoints, the efficacy of these agents (oltipraz, chlorophyllin, broccoli sprout beverages) has been demonstrated, highlighting roles for frugal approaches to chemoprevention against environmental carcinogenesis. Remarkably, recent evidence garnered from retrospective analysis of archived serum samples from the past quarter century demonstrates a 40-fold drop in aflatoxin exposure in Qidong, likely driven by changes in the primary dietary staple from maize to rice. Thus, primary prevention, evoked by changing economic and agricultural policies in the 1980s, heralds the unanticipated promise of elimination of liver cancer from this endemic region in a fore-shortened timeframe.
黄曲霉毒素-N7 鸟嘌呤
aflatoxin-N7-guanine
[1] Ferlay J, Shin H R, Bray F, Forman D, Mathers C, Parkin D M. Int. J. Cancer, 2010, 127: 2893—917
[2] Zhu Y R, Chen J G, Huang X Y. Primary Liver Cancer (Eds. Tang Z Y, Wu M C, Xia S S). Beijing: China Academic Publishers, Springer-Verlag, 1989, 204—222
[3] Yu S Z. J. Gastroenterol. Hepatol., 1995, 10: 674—682
[4] Kensler T W, Qian G S, Chen J G, Groopman J D. Nat. Rev. Cancer, 2003, 3: 321—329
[5] Qian G S, Ross R K, Yu M C, Yuan J M, Gao Y T, Henderson B E, Wogan G N, Groopman J D. Cancer Epidemiol. Biomarkers Prev. 1994, 3: 3—10
[6] Ming L, Thorgeirsson S S, Gail M H, Lu P, Harris C C, Wang N, Shao Y, Wu Z, Liu G, Wang X, Sun Z. Hepatology, 2002, 36: 1214—1220
[7] Lu P, Kuang S Y, Wang J B, Fang X, Zhang Q N, Wu Y, Lu Z, Qian G S. National Medical Journal of China, 1998, 78: 340—342
[8] Sun T T, Chu Y R, Ni Z Q, Lu J H, Fei H, Ni Z P, Pei X F, Yu Z I, Liu G T. J. Cell Physiol. Suppl., 1986, 4: 83—90
[9] Kensler T W, Roebuck B D, Wogan G N, Groopman J D. Toxicol. Sci., 2011, 120: 28—48
[10] Eaton D L, Gallagher E P. Annu. Rev. Pharmacol. Toxicol., 1994, 34: 135—172
[11] Groopman J D, Kensler T W. Carcinogenesis, 1999, 20: 1—11
[12] Groopman J D, Zhu J Q, Donahue P R, Pikul A, Zhang L S, Chen J S, Wogan G N. Cancer Res., 1992, 52: 45—52
[13] Roebuck B D, Liu Y L, Rogers A E, Groopman J D, Kensler T W. Cancer Res., 1991, 51: 5501—5506
[14] Groopman J D, DeMatos P, Egner P A, Love-Hunt A, Kensler T W. Carcinogenesis, 1992, 13: 101—106
[15] Wild C P, Gong Y Y. Carcinogenesis, 2010, 31: 71—82
[16] Kensler T W, Groopman J D, Wogan G N. IARC Scientific Publication No. 139: Principles of Chemoprevention (Eds. Stewart B W, McGregor D, Kleihues P), IARC, Lyon, 1996, 237—248
[17] Sofowora G G, Choo E F, Mayo G, Shyr Y, Wilkinson G R. Cancer Chemother. Pharmacol., 2001, 47: 505—510
[18] Gupta E, Olopade O I, Ratain M J, Mick R, Baker T M, Berezin F K, Benson A B 3rd, Dolan M E. Clin. Cancer Res., 1995, 1: 1133—1138
[19] O'Dwyer P J, Szarka C E, Yao K S, Halbherr T C, Pfeiffer G R, Green F, Gallo J M, Brennan J, Frucht H, Goosenberg E B, Hamilton T C, Litwin S, Balshem A M, Engstrom P F, Clapper M L. J. Clin. Invest., 1996, 98: 1210—1217
[20] Jacobson L P, Zhang B C, Zhu Y R, Wang J B, Wu Y, Zhang Q N, Yu L Y, Qian G S, Kuang S Y, Li Y F, Fang X, Zarba A, Chen B, Enger C, Davidson N E, Gorman M B, Gordon G B, Prochaska H J, Egner P A, Groopman J D, Muñoz A, Helzlsouer K J, Kensler T W. Cancer Epidemiol. Biomarkers Prev., 1997, 6: 257—265
[21] Wang J S, Shen X, He X, Zhu Y R, Zhang B C, Wang J B, Qian G S, Kuang S Y, Zarba A, Egner P A, Jacobson L P, Muñoz A, Helzlsouer K J, Groopman J D, Kensler T W. J. Natl. Cancer Inst., 1999, 91: 347—354
[22] Fahey J W, Talalay P, Kensler T W. Cancer Prev. Res., 2012, 5: 179—188
[23] Dashwood R. Int. J. Oncol., 1997, 10: 721—727
[24] Breinholt V, Schimerlik M, Dashwood R, Bailey G. Chem. Res.Toxicol., 1995, 8: 506—514
[25] Fahey J W, Stephenson K K, Dinkova-Kostova A T, Egner P A, Kensler T W, Talalay P. Carcinogenesis, 2005, 26: 2605—2613
[26] Egner P A, Wang J B, Zhu Y R, Zhang B C, Wu Y, Zhang Q N, Qian G S, Kuang S Y, Gange S J, Jacobson L P, Helzlsouer K J, Bailey G S, Groopman J D, Kensler T W. Proc. Natl. Acad. Sci. U.S.A., 2001, 98: 14601—14606
[27] Jubert C, Mata J, Bench G, Dashwood R, Pereira C, Traacewell W, Turteltaub K, Williams D, Bailey G. Cancer Prev. Res., 2009, 2: 1015—1022
[28] Shapiro T A, Fahey J W, Dinkova-Kostova A T, Holtzclaw W D, Stephenson K K, Wade K L, Ye L, Talalay P. Nutr. Cancer, 2006, 55: 53—62
[29] Egner P A, Chen J G, Wang J B, Wu Y, Sun Y, Lu J H, Zhu J, Zhang Y H, Chen Y S, Friesen M D, Jacobson L P, Muñoz A, Ng D, Qian G S, Zhu Y R, Chen T Y, Botting N P, Zhang Q, Fahey J W, Talalay P, Groopman J D, Kensler T W. Cancer Prev. Res., 2011, 4: 384—395
[30] Shapiro T A, Fahey J W, Wade K L, Stephenson K K, Talalay P. Cancer Epidemiol. Biomarkers Prev., 2001, 10: 501—508
[31] Kensler T W, Chen J G, Egner P A, Fahey J W, Jacobson L P, Stephenson K K, Ye L, Coady J L, Wang J B, Wu Y, Sun Y, Zhang Q N, Zhang B C, Zhu Y R, Qian G S, Carmella S G, Hecht S S, Benning L, Gange S J, Groopman J D, Talalay P. Cancer Epidemiol. Biomarkers Prev., 2005, 14: 2605—2613
[32] http://www.china-food-security.org/data/maps/crops/all_h.htm:[December 2012]
[33] London W T, Evans A A, McGlynn K, Buetow K, An P, Gao L L, Lustbader E, Ross E, Chen G C, Shen F M. Interverology, 1995, 38: 155—161
[34] Chen J G. Chin. J. Can. Prev. Treat., 2003, 10: 1123—1125
[35] Scholl P F, Groopman J D. Cancer Epidemiol. Biomarkers Prev., 2008, 17: 1436—1439
[36] Chen G G, Egner P A, Ng D, Jacobson L P, Munoz A, Zhu Y R, Qian G S, Wu F, Yuan J M, Groopman J D, Kensler T W. Cancer Prev. Res., 2013, DOI: 10.1158/1940-6207.CAPR-13-0168
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