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血清有机氯杀虫剂浓度与原发性肝癌的关系:两项前瞻性队列嵌套病例对照研究。

Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

机构信息

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.

出版信息

Int J Cancer. 2019 Nov 1;145(9):2360-2371. doi: 10.1002/ijc.32175. Epub 2019 Feb 14.

Abstract

Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.

摘要

尽管实验证据表明某些有机氯杀虫剂是肝癌致癌物,但大多数此类化学物质的流行病学证据非常有限。我们使用前瞻性收集的血清,在两个队列中估计了有机氯杀虫剂浓度与癌症登记处确定的原发性肝癌之间的关联,一个队列来自美国,另一个来自挪威。在嵌套病例对照研究中,我们使用了来自 Kaiser Permanente 北加利福尼亚多相健康检查(MHC)队列的 136 例病例和 408 例匹配对照以及来自基于人群的挪威 Janus 队列的 84 例病例和 252 例匹配对照的 20 世纪 60 年代至 80 年代收集的血清。我们测量了血清中的九种有机氯杀虫剂/代谢物和乙型肝炎和丙型肝炎标志物的浓度。使用条件逻辑回归,为每个队列计算了脂质校正的有机氯三价的调整比值比(OR)和 95%置信区间(CI)。在 MHC 参与者中,血清来自 20 世纪 60 年代,顺式非那氯(分析物第二和第三三分位数的 OR 分别为 1.63 和 1.95;趋势 p 值= 0.08)存在提示性暴露-反应趋势,而氧氯丹的最高三分位数的风险略有升高(OR = 1.87)。在来自 20 世纪 70 年代的 Janus 参与者中,我们观察到 p,p'-DDT 似乎呈趋势(第二和第三三分位数 OR 分别为 1.70 和 2.14;趋势 p 值= 0.15)。我们发现两个队列之间的关联模式几乎没有一致性。我们发现有限的证据表明,接触 p,p'-DDT 和氯丹相关的氧氯丹和顺式非那氯可能与原发性肝癌风险增加有关。然而,这些关联的适度强度及其在队列之间缺乏一致性,需要谨慎解释。

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