陈一文：国际癌症研究所科学家研究：草甘膦提高NHL血癌风险一倍

　　陈一文：国际癌症研究所科学家研究：草甘膦提高NHL血癌风险一倍

　　(2015-07-17 12:25:16)

　　非霍奇金淋巴瘤 血浆细胞肿瘤 多发性骨髓瘤 慢性淋巴细胞性白血病婴儿配方乳粉

　　分类： 批判转基因技术

　　非霍奇金淋巴瘤(NHL)发生率过去30年惊人增加。世界卫生组织(WHO)国际癌症研究所(IARC)的科学家发现暴露于农药与非霍奇金淋巴瘤血癌之间强烈关联。分析了1980年以来公开发表的44项不同研究后，这些科学家在《环境性研究与公共健康国际杂志》发表论文确认：暴露于草甘膦除草剂提高非霍奇金淋巴瘤血癌风险一倍!非霍奇金淋巴瘤(NHL)的分类系统随着时间也发生了变化，反映了疾病定义中的变化。2000年以后，非霍奇金淋巴瘤的定义已经成为更加综合性。其定义目前包括了早期定义中排除的某些疾病类别，例如血浆细胞肿瘤(多发性骨髓瘤)与慢性淋巴细胞性白血病。这些恶性肿瘤也是非霍奇金淋巴瘤中经常报告的亚型。

　　Scientists at the International Agency for Research on Cancer have found what appears to be a strong link between pesticide exposure and a blood cancer called non-Hodgkin lymphoma. Analyzing 44 individual research projects published since 1980, the scientists, writing in the International Journal of Environmental Research and Public Health, said that people exposed to the weed killer glyphosate, marked by Monsanto under the brand name Roundup, had double the risk of developing non-Hodgkin’s lymphoma. NHL classification systems have changed over time, reflecting changes in disease definitions. Recently (after year 2000), the definition of NHL has become more comprehensive. The definition now includes disease entities that were excluded from earlier definitions, such as plasma cell neoplasms (i.e., multiple myeloma) and chronic lymphocytic leukemia. These malignancies are also among the most frequently reported sub-types within NHL.

　　Leah Schinasi, Maria E. Leon, Non-Hodgkin Lymphoma and Occupational Exposure to Agricultural Pesticide Chemical Groups and Active Ingredients: A Systematic Review and Meta-Analysis, Int J Environ Res Public Health. 2014 Apr; 11(4): 4449–4527.Leah Schinasi, Maria E. Leon，非霍奇金淋巴瘤和职业接触农业农药化学品组和活性成分：系统回顾和荟萃分析，环境研究公共卫生国际杂志，2014年4月;11(4): 4449–4527http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025008/#B10-ijerph-11-04449/

　　全文：http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025008

　　Author Information:

　　作者信息：

　　rf.crai.swollef@lisanihcs

　　Abstract:

　　摘要：

　　This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed.

　　本文描述近三十年来对非霍奇金淋巴瘤(NHL)与职业性暴露于农药活性成分与化学品组之间关系流行病学研究系统性审查与一系列荟萃分析结果。从44篇论文提取了对非霍奇金淋巴瘤(NHL)与21中农药化学品组与80种活性成分关联的估计，这些论文报告了对高收入国家中研究进行分析的结果。对随意性影响的荟萃分析表明，含苯氧基的除草剂、氨基甲酸酯杀虫剂、有机磷杀虫剂以及活性成分林丹，一种有机氯杀虫剂，都与非霍奇金淋巴瘤(NHL)阳性相关。多篇论文中，报告了农药与非霍奇金淋巴瘤(NHL)的一种亚种关联;B细胞淋巴瘤与暴露于含苯氧基的除草剂和有机磷除草剂阳性关联。弥漫型大b细胞淋巴瘤与暴露于含苯氧基的除草剂阳性关联。尽管有令人信服的证据表明非霍奇金淋巴瘤(NHL)与某些化学品关联，该项审查表明需要对更多地理区域中更多类别农药进行调查，特别在低收入与中等收入国家，尽管这些国家占世界农药很大比例，有关文献中缺乏这些地区的资料。

　　1. Introduction

　　1、引言

　　Striking increases in the incidence of non-Hodgkin lymphoma (NHL) cancer have occurred in the last 30 years [1,2], and interest in identifying environmental and occupational exposures associated with this cancer has accompanied this trend. Several environmental exposures have been proposed and investigated as potentially important—pesticides, dioxins, solvents, oils, and viruses, among others [3,4]. Farmers experience low overall mortality but high rates of some cancers; this suggests that some or several agricultural exposures may be key determinants [5,6]. Indeed, positive associations between NHL and farm related exposures, including pesticides, fertilizers, chemicals, animals, viruses, and endotoxin, have been observed previously [3,5,7]. However, the wide variety of chemical and microbial exposures that occur simultaneously in agricultural production makes disentangling the effects of these factors challenging. Of the many exposures experienced in farm settings, pesticides have drawn particular attention, especially since the increased incidence of NHL in the mid- to late-1900s followed widespread use of synthetic organic pesticides [4]. Also, several epidemiologic studies have reported positive associations between NHL and pesticide exposure in occupational manufacturing settings [8,9].

　　非霍奇金淋巴瘤(NHL)发生率过去30年惊人增加[1,2]，力图搞清这种环境性与职业性暴露于这种癌症之间的关联的兴趣随这种趋势的发展愈强。已经提出数种环境性暴露潜在重要并进行调查 -- 其中包括农药、二恶英、溶剂、油，以及病毒等[3,4]。农民总死亡率较低，但是遭遇某些癌症高发生率;这提议，某些或者数种农业性暴露可能是关键因素[5,6]。确实，非霍奇金淋巴瘤(NHL)与某些农场相关的暴露阳性关联，包括以前观察过的农药、化肥、化学品、动物、病毒，与内毒素[3,5,7]。然而，农业生产中同时发生的广泛种类化学品与微生物暴露，使得分离这些因素的影响颇具挑战性。在农场条件下遭遇的许多暴露中，对农药引起特别关注，特别因为上世纪中期到后期广泛使用合成有机农药后非霍奇金淋巴瘤(NHL)发生率急剧增高[4]。而且，数项流行病学研究报告了非霍奇金淋巴瘤(NHL)与职业性制造中的农药暴露之间阳性关联[8,9]。

　　The United States Environmental Protection Agency defines pesticides as substances intended to prevent, destroy, repel, or mitigate a pest [10]. Within this broad category, pesticides are often grouped according to the type of pests that they control; for example, fungicides are used to kill fungi, insecticides to kill insects, and herbicides to kill weeds and plants. In addition to function, pesticides vary in terms of structure, and they are sometimes grouped according to chemical relationships. Furthermore, applicators often use a variety of pesticides simultaneously. These characteristics make designing and conducting epidemiologic studies of their health effects both challenging and expensive.

　　美国环保署定义农药为防止、摧毁、排斥，或者减轻一种有害物的物质[10]。在这种广阔的类别中，往往将农药依照它们治理的害虫进行分类;例如，杀真菌剂用来杀死真菌，杀虫剂用来杀死害虫，除草剂用来杀死野草与植物。除了以功能分类，农药还以结构不同，有时一化学性关系分组。此外，使用者往往同时使用不同的农药。这些特征，使得设计与进行对其健康影响的流行病学研究既具挑战性又很昂贵。

　　Because pesticides are thought to have different toxicologic and immunologic effects, identifying the chemicals and chemical groups that are most dangerous to humans and non-target living organisms is important [11]. From a research perspective, the decision about what chemicals to investigate has implications for disease prevention, and it impacts the information that is available to policy makers and the public.

　　由于农药被认为具有不同的毒理学与免疫性影响，将对于人类与非靶生物最危险的化学品与化学品组识别出来非常重要[11]。从研究角度，对那些化学品进行调查的决定对相关疾病预防关系重大，而且对政策制定者与公众能够获得哪些信息造成影响。

　　These challenges and needs motivated us to systematically review the published epidemiologic literature of relationships of NHL with occupational exposures to agricultural pesticide chemical groups and active ingredients. The primary objectives of this paper were to investigate the depth of the literature on the relationship between specific pesticide chemicals and NHL, to identify gaps in this area of research, and to elucidate pesticide chemical groups and active ingredients that have shown particularly strong relationships with NHL. To help us to achieve these objectives, we conducted a series of meta-analyses of associations of individual pesticide chemicals with NHL.

　　这些挑战与需要推动我们审查已发表的非霍奇金淋巴瘤(NHL)与职业性暴露于农药化学品组与活性成分之间关系有关的流行病学文献。这篇论文的基本目的是研究有关特定农药化学品与非霍奇金淋巴瘤(NHL)之间关系文献的深度，识别这些领域研究中的空白，以及阐明哪些农药化学品组与活性成分特别显示与非霍奇金淋巴瘤(NHL)之间强烈关系。为帮助我们实现这些目标，我们对不同农药化学品与非霍奇金淋巴瘤(NHL)之间的关联进行了一系列荟萃分析。

　　McDuffie et al.[43] and Eriksson et al. [32] observed increased odds of NHL in association with a greater number of days/year of glyphosate exposure.De Roos et al. [31] did not observe a similar relationship in analyses of Agricultural Health Study data.

　　McDuffie et al.[43] 与Eriksson et al. [32]的研究观察到非霍奇金淋巴瘤(NHL)与每年暴露于草甘膦的天数增多之间关联优势比增加。然而，De Roos et al. [31]对于农药健康研究数据的分析中没有观察到类似的关系。

　　Table 5 Meta analytic summary estimates of association between herbicides and insecticides with non-Hodgkin lymphoma.

　　表5、对草甘膦与杀虫剂与非霍奇金淋巴瘤(NHL)之间关联总结的预计的荟萃分析

　　The strongest meta RR estimates were associated with subtypes of NHL. There was a positive association between exposure to organophosphorus herbicide, glyphosate, and B cell lymphoma (2.0, 95% CI: 1.1–3.6, CLR: 3.2).

　　最强的荟萃风险比(Risk Ratio)预计是与非霍奇金淋巴瘤(NHL)的亚型之间的管理。对有机磷除草剂草甘膦的暴露与B细胞淋巴瘤阳性关联(2.0, 95% CI: 1.1–3.6, CLR: 3.2)。

　　Finally, NHL classification systems have changed over time, reflecting changes in disease definitions [1]. Recently (after year 2000), the definition of NHL has become more comprehensive. The definition now includes disease entities that were excluded from earlier definitions, such as plasma cell neoplasms (i.e., multiple myeloma) and chronic lymphocytic leukemia. These malignancies are also among the most frequently reported sub-types within NHL [65]. Thus, estimates of association between pesticides and overall NHL from studies conducted in earlier periods may not be entirely comparable to estimates from research conducted since the year 2000 that used the updated NHL definition.

　　最后，非霍奇金淋巴瘤(NHL)的分类系统随着时间也发生了变化，反映了疾病定义中的变化[1]。最近(2000年以后)，非霍奇金淋巴瘤(NHL)的定义已经成为更加综合性。其定义目前包括了早期定义中排除的某些疾病类别，例如血浆细胞肿瘤(即，多发性骨髓瘤)与慢性淋巴细胞性白血病。这些恶性肿瘤也是非霍奇金淋巴瘤(NHL)中经常报告的亚型[65]。因此，来自早期研究的农药与总非霍奇金淋巴瘤(NHL)之间的关联的预计可能与来自2000年以后采用更新非霍奇金淋巴瘤(NHL)定义的研究的预计不完全可比。

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　　1)中国儿童白血病年增2万患儿剧增到年增4万患儿，已成为流行病态势!

　　博文：http://t.cn/RL7RuMc; 微博：http://weibo.com/1269923485/Cpi7GvF4b

　　网友汇总巨量白血病患儿信息令人深思!2011年报道，我国400万名白血病患者中，50%是儿童，以2—7岁患儿居多。2012年，中国血液病协会委员、济南血液病医院首席专家王佐庭介绍，目前中国约有500万白血病患者，儿童白血病患者约占一半，白血病患者数量的增长速度从过去每年约4万人提高到每年约8万人。也就是说，中国儿童白血病年增2万患儿剧增到年增4万患儿，已成为流行病态势!据济南血液病医院企划部主任周华介绍，目前很多白血病等血液病患者来自农村，经济条件比较困难。“治疗少则几十万、多则上百万元，光做骨髓移植手术就要三四十万元。” 依照儿童白血病患儿平均治疗费用50万元推测，年增4万患儿意味着每年合计增加治疗费用200亿元，还不算对患儿家长造成的其他经济负担。

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　　美国新泽西州立大学药理学和毒理学罗伯特-斯奈德博士回顾了医学与毒理学界对苯造成白血病认识与研究的最新进展，对未来研究方向提出了建议。他强调“近年来关注到的苯接触造成的另一种结果，是一种或多种类型白血病的发展。虽然许多调查人员认为，在肝脏或骨髓生成的苯的数种有毒代谢物组合，可能导致创伤性骨髓损伤，然而，导致白血病的更微妙的机制尚未深刻揭示出来。”文章引证美国环保署(EPA)1998年4月颁布的《苯的致癌作用：更新》，确认对苯的毒性而言，即便“在极端低的剂量的每种剂量都可以关联与某种特定的风险”，某些人士热衷于“人类流行病学研究或者动物生物试验找到一种不造成风险的可接受的苯安全剂量水平的努力”至今失败。这充分证实：人类，特别是婴儿与儿童，日复一日、月复一月食用的食品及其相关标准，对苯的残留必须坚持“零容忍”，因为持续摄入哪怕极其微量苯残留，必然造成白血病剧增的恶果!

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　　美国新泽西州立大学药理学和毒理学罗伯特-斯奈德博士揭示，多种白血病的根源是有害化学物质导致创伤性骨髓及其造血系统损伤。2004年世界粮农组织/世界卫生组织对农药残留会议文件确认孟山都1988年与先正达1996年向世界卫生组织提交的文件确认：用碳14辐射标记草甘膦服用给大鼠时，试验期间内，无论不同剂量、服用方式或者服用次数，服用剂量的0.5-1.4%留在了组织中。最高的放射性在骨头，其次在骨髓、肾脏、肝脏、肺部与残留的骨骼!文件确认的孟山都1988年提交给世界卫生组织的孟山都环境性健康实验室1983年完成的大鼠草甘膦服用研究报告意义重大，证实孟山都农达1988年向中国农业部申请“农药登记”时，孟山都早在1983年通过动物试验已经清楚知道草甘膦在哺乳动物骨髓生物蓄积，而不是不生物蓄积!

　　4)孟山都1983年做的毒理学动物试验证实草甘膦致白血病

　　博文：http://t.cn/RLqpE4s; 微博：http://weibo.com/1269923485/Cr2na6C8s

　　孟山都1988年申请农达“农药登记”时对中国政府与中国的第三方面欺骗：故意没向农业部提供暴露草甘膦致癌性的长期、终生与三代生殖毒性动物试验报告。美国环保署(EPA)对草甘膦除草剂做安全评价期间，向美国环保署提交的孟山都委托Biodynamics实验室对SD大鼠所做的26个月试验研究，所有不同剂量草甘膦处理组睾丸中都发现了间质细胞肿瘤，但是对照组中没有发现任何肿瘤。低、中与高剂量草甘膦组中致瘤发病率增长为6%、2%与12%。肾脏中发现良性肾小管腺瘤，在雄鼠的心脏、脾、胰腺、肺、肝、淋巴结、骨髓与肾上腺中发现白血病症状的淋巴母细胞性淋巴肉瘤。在乳腺中发现导管腺癌，子宫中发现平滑肌肉瘤。发现的其他种类癌症为：支气管肺泡腺癌、颗粒细胞瘤、平滑肌肉瘤血管内皮瘤、粒细胞性白血病和复合淋巴肉瘤。大多数的癌症是转移性的或恶性，有些是良性的。依据孟山都要求，这些动物试验研究文件作为商业秘密对公众保密。孟山都1988年申请农达“农药登记”时故意不提供这些动物试验报告。

　　5)瑞典2002论文揭草甘膦增加白血病风险孟山都耍赖否认

　　博文：http://t.cn/RL5r5nl 微博：http://weibo.com/1269923485/Crcx8xYAy

　　《白血病淋巴瘤》杂志2002年5月发表瑞典科学家Nordstrom等人论文，揭示草甘膦增加非霍奇金淋巴瘤和毛细胞白血病的风险，在世界造成轰动。2002年8月，孟山都急忙发布辩解并指控“没有能够证实这种发现的长期动物试验研究实验证据。”然而，美国环保署(EPA)对草甘膦除草剂做安全评价期间，孟山都向美国环保署提交的孟山都委托Biodynamics实验室对SD大鼠所做的26个月试验研究揭示“在雄鼠的心脏、脾、胰腺、肺、肝、淋巴结、骨髓与肾上腺中发现白血病症状的淋巴母细胞性淋巴肉瘤。...粒细胞性白血病和复合淋巴肉瘤。”而且，正是依据孟山都要求，美国环保署(EPA)将这些动物试验研究文件作为“商业秘密”封存对公众保密。孟山都如果对“草甘膦不致癌、不致白血病”信心满满，孟山都应当同意美国环保署公布孟山都提交的对草甘膦所做的所有长期、多代动物试验报告。

　　转基因大豆死刑：美国麻省理工学院科学家研究揭转基因大豆积蓄致癌甲醛

　　博文：http://t.cn/RLtIMhgl http://weibo.com/1269923485/Crf50EEvY

　　同行审查刊物《农业科学》2015年7月14日发表的一项新的研究揭示转基因大豆干扰作物控制压力的自然能力，发现公认致癌物甲醛在转基因大豆中积蓄，同时发现细胞解毒所必需的抗氧化剂谷胱甘肽在转基因大豆中耗竭。该项研究由麻省理工学院培养的系统生物学家V.A. Shiva Ayyadurai博士领衔。美国环保署前高级科学家Ray Seidler博士强调：“甲醛是公认的一级致癌物。普遍的转基因大豆品种存在着水平升高的甲醛令人警觉，值得FDA和奥巴马政府关注和立即采取行动。大豆在美国广泛种植与食用，包括婴儿配方食品，而94%的大豆已经转基因”。该项研究结论：美国政府目前基于“实质等同”原则的转基因生物安全性评估标准，已经过时与不科学，使食品药物管理署对转基因食品安全性标准陷入问题。这篇论文的发表，与奥巴马政府2015年7月2日呼吁“改善生物技术的透明性并保证持续安全性”文告发布的时间巧合。