Kelly Rachel S, Kiviranta Hannu, Bergdahl Ingvar A, Palli Domenico, Johansson Ann-Sofie, Botsivali Maria, Vineis Paolo, Vermeulen Roel, Kyrtopoulos Soterios A, Chadeau-Hyam Marc
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
Environ Health. 2017 Feb 16;16(1):9. doi: 10.1186/s12940-017-0214-8.
Evidence suggests a largely environmental component to non-Hodgkin's lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined.
The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers.
The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (p < 0.05) in median exposure levels between cases and controls for any of the investigated exposures. However under a multivariate model PCB138, PCB153, HCB and DDE displayed significant inverse trends (Wald test p-value <0.05). Under stratified analyses these were determined to be driven by males and by the Diffuse Large B-Cell Lymphoma subtype. When considering those in the highest levels of exposure (>90 percentile) the association was null for all POPs CONCLUSION: We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL.
有证据表明非霍奇金淋巴瘤（NHL）很大程度上受环境因素影响。包括多氯联苯（PCBs）、滴滴涕（DDE）和六氯苯（HCB）在内的持久性有机污染物（POPs）多次被提及，但文献报道并不一致，因果关系仍有待确定。
环境基因标记物研究嵌套于两项前瞻性队列研究——意大利欧洲癌症与营养前瞻性调查（EPIC-Italy）和瑞典北部健康与疾病研究。使用气相色谱 - 质谱法对招募时提供的血浆样本中的六种多氯联苯同系物、滴滴涕和六氯苯进行测量。在16年的随访期间，诊断出270例B细胞非霍奇金淋巴瘤（包括76例多发性骨髓瘤）病例。根据中心、年龄、性别和采血日期，将病例与270名健康对照进行匹配。根据对照人群中暴露的分布情况，将病例按每种持久性有机污染物的暴露水平分为有序四分位数。应用逻辑回归评估与风险的关联，进行多变量和分层分析以识别混杂因素或效应修饰因素。
这些暴露显示出高度的相关性，特别是在氯化程度相似的多氯联苯之间。对于任何所研究的暴露，病例组和对照组的中位暴露水平均无显著差异（p < 0.05）。然而，在多变量模型下，多氯联苯138、多氯联苯153、六氯苯和滴滴涕呈现出显著的负相关趋势（Wald检验p值 < 0.05）。在分层分析中，这些趋势被确定是由男性和弥漫性大B细胞淋巴瘤亚型驱动的。当考虑暴露水平最高（>第90百分位数）的人群时，所有持久性有机污染物的关联均无统计学意义。结论：我们没有发现证据表明体内多氯联苯、滴滴涕或六氯苯负担增加会增加随后患非霍奇金淋巴瘤的风险。对于男性，一些所研究的持久性有机污染物呈现出显著的负相关。我们推测这些意外关系可能与我们人群的亚型组成、体重指数的效应修饰或其他未测量的混杂因素有关。本研究没有为先前观察到的多氯联苯、滴滴涕和六氯苯作为非霍奇金淋巴瘤风险因素的作用提供额外支持。
