Engel Lawrence S, Laden Francine, Andersen Aage, Strickland Paul T, Blair Aaron, Needham Larry L, Barr Dana B, Wolff Mary S, Helzlsouer Kathy, Hunter David J, Lan Qing, Cantor Kenneth P, Comstock George W, Brock John W, Bush David, Hoover Robert N, Rothman Nathaniel
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer Res. 2007 Jun 1;67(11):5545-52. doi: 10.1158/0008-5472.CAN-06-3906.
The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.
在过去几十年中，与HIV感染无关的非霍奇金淋巴瘤（NHL）发病率稳步上升，其原因仍很大程度上不明。有限的证据表明，血液或脂肪组织中多氯联苯（PCB）浓度升高与NHL风险增加有关。尽管PCB同系物的生物活性各不相同，但此前尚未使用前瞻性收集的生物标本研究个体同系物与NHL风险之间的关系。我们在三个前瞻性队列中研究了同系物特异性关联。在这些队列的NHL病例和对照中测量了选定PCB同系物的诊断前血清或血浆浓度：挪威的贾纳斯队列（190例病例和190例对照）以及美国的CLUE I队列（74例病例和147例对照）和护士健康研究队列（30例病例和78例对照）。所有血液样本均在20世纪70年代或80年代采集。我们使用逻辑回归计算NHL风险与脂质校正血浆或血清浓度之间关系的比值比（OR）和95%置信区间（95%CI）。几种浓度较高且相互之间中度至高度相关的同系物（即118、138和153）在所有三个队列中均显示出与NHL风险的暴露-反应趋势。这些关联主要在两个有足够病例允许按时间分层的队列中，在更接近血液采集日期诊断的受试者中观察到。在随访中位数年份（贾纳斯队列为16年，CLUE I队列为12年）内诊断的病例中，相对于最低四分位数，同系物118浓度每增加四分位数的OR和95%CI如下：贾纳斯队列中为2.4（0.9 - 6.5）、4.9（1.6 - 15.3）和5.3（1.5 - 18.8；P趋势<0.005），CLUE I队列中为8.1（1.0 - 68.9）、6.6（0.7 - 59.0）和13.0（1.6 - 106.8；P趋势<0.05）。同系物138和153以及总PCB也观察到类似模式。其他几种同系物也观察到有限的暴露-反应趋势证据。主要的1,1,1-三氯-2,2-双（对氯苯基）乙烷代谢物p,p'-DDE在大多数分析中与NHL无显著关联，但对PCB关联有轻微至中度的混杂作用。这三个队列的结果表明，血液中某些PCB的浓度与NHL风险增加有关。
