PO.PS01.12 · 人群科学

炎症相关暴露与组织学类型特异性卵巢癌风险：卵巢癌协会联盟（OCAC）

Inflammation-related exposures and histotype- specific ovarian cancer risk in the Ovarian Cancer Association Consortium (OCAC)

编号 6261 展板 23 时间 4/21 02:00–05:00 区域 Section 33 主讲 Maxwell Akonde, BS

分会场 Environmental and Occupational Risk Factors, Infection, and Aging

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作者与单位 Authors & Affiliations

Maxwell Akonde¹, Britton Trabert², SHELLEY TWOROGER³, Allan Jensen⁴, Kathryn L. Terry⁵, Joshua Sampson⁶, Hoda Anton-Culver⁷, David Bowtell⁸, Elisa V. Bandera⁹, Angela Brooks-Wilson¹⁰, Andrew Berchuck¹¹, Daniel William Cramer¹², Linda S. Cook¹³, Julie M. Cunningham¹⁴, Jennifer A. Doherty¹⁵, Ellen L. Goode¹⁶, Marc T. Goodman¹⁷, Holly Ruth Harris¹⁸, Susanne K. Kjaer¹⁹, Nhu Le²⁰, Alice Wen-Ron Lee²¹, Francesmary Modugno²², Kirsten B. Moysich²³, Celeste Pearce²⁴, Malcolm C. Pike²⁵, Harvey A. Risch²⁶, Mary A. Rossing²⁷, Joellen M. Schildkrau²⁸, Daniel O. Stram²⁹, Rebecca Sutphen³⁰, David Van Den Berg³¹, Penelope M. Webb³², Anna Wu³³, Argyrios Ziogas³⁴, Nicolas A. Wentzensen³⁵

¹Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD,²University of Utah Huntsman Cancer Institute, Salt Lake City, UT,³Oregon Health and Science University, Knight Cancer Institute, Portland, OR,⁴Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark,⁵Asst. Professor, Dept. of OB/GYN, Brigham and Women's Hospital, Boston, MA,⁶Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rocville, MD,⁷Chair & Professor, Dept. of Epidemiology, Department of Medicine, Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, CA,⁸Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Australia,⁹Rutgers Cancer Institute of New Jersey, New Brunswick, NJ,¹⁰Head, Cancer Genetics, BC Cancer Research Centre, Vancouver, BC, Canada,¹¹Duke University Medical Center, Durham, NC,¹²Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,¹³Epidemiology, School of Public Health, University of Colorado, Aurora, CO,¹⁴Mayo Clinic College of Medicine and Science, Rochester, MN,¹⁵Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT,¹⁶Mayo Clinic, Rochester, MN,¹⁷Cedars-Sinai Medical Center, Los Angeles, CA,¹⁸Fred Hutchinson Cancer Center, Seattle, WA,¹⁹Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark,²⁰Cancer Control Research, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada,²¹California State University, Fullerton, Fullerton, CA,²²Womens Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA,²³Professor, Dept. of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY,²⁴Univ. of Michigan School of Public Health, Ann Arbor, MI,²⁵Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY,²⁶Professor, Dept. of Epidemiology & Public Health, Yale Univ. School of Medicine, New Haven, CT,²⁷Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA,²⁸Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA,²⁹Department of Preventive Medicine, University of Southern California, Los Angeles, CA,³⁰Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL,³¹Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA,³²Queensland Institute of Medical Research, Herston, Australia,³³Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA,³⁴Department of Medicine, Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, CA,³⁵NCI Div. of Cancer Epidemiology & Genetics, Bethesda, MD

摘要 Abstract

中文摘要

背景：慢性炎症被认为参与卵巢癌发生，但不同的炎症相关暴露如何单独或共同影响组织学类型特异性关联仍不明确。材料与方法：我们汇总了卵巢癌协会联盟中16项病例对照研究的数据，以评估八种炎症相关因素（抗炎：阿司匹林使用、输卵管结扎（TL）；促炎：子宫内膜异位症、肥胖、终生排卵周期数（LOC）、吸烟、盆腔炎性疾病（PID）、多囊卵巢综合征（PCOS））与上皮性卵巢癌（OvC）按组织学亚型的关联。我们考察了各风险因素的个体关联及其在各组织学类型间的聚类，并计算了各因素的人群归因风险（PAR）。我们评估了暴露组合的加性和乘性交互作用。结果：与OvC风险的关联因组织学类型而异（例如，高级别浆液性：阿司匹林：OR=0.90；95%CI 0.82, 0.99；TL：OR=0.80；95%CI 0.73, 0.88；总体浆液性：子宫内膜异位症：OR=1.17；95%CI 1.03, 1.31；高LOC：OR=1.42；95%CI 1.28, 1.58；肥胖（低级别浆液性）：OR=1.50；95%CI 1.14, 1.98）。聚类分析显示子宫内膜样和透明细胞的风险特征高度相关（r=0.91）。高级别浆液性和黏液性特征与子宫内膜样和透明细胞肿瘤中度相关（r=0.60）。低级别浆液性（r=0.36）肿瘤的特征与其他组织学类型不同。PAR估计提示，改变阿司匹林使用、TL和LOC可显著降低子宫内膜样、透明细胞和黏液性肿瘤的负担。在总体OvC中测试的28种暴露组合以及按组织学类型的189种组合中，我们观察到12种交互作用。不规律使用阿司匹林与肥胖和高LOC呈现正向加性交互作用，尤其在子宫内膜样肿瘤中（肥胖交互作用所致相对超额风险（RERI）=0.74，95%CI 0.31, 1.18；P int =0.001；LOC RERI=0.80，95%CI 0.03, 1.56；P int =0.04）。不规律使用阿司匹林在透明细胞肿瘤中也与子宫内膜异位症呈现正向加性交互作用（RERI=1.77，95%CI 0.03, 3.52；P int =0.05）。缺乏TL在子宫内膜样（RERI=0.86，95%CI 0.17, 1.53；P int =0.01）和黏液性（RERI=1.10，95%CI 0.23, 1.97；P int =0.01）肿瘤中与肥胖呈现正向交互作用，而在子宫内膜样肿瘤中观察到吸烟与子宫内膜异位症的负向加性交互作用（RERI=-1.12，95%CI -2.19, -0.05；P int =0.04）。在黏液性肿瘤中观察到肥胖与子宫内膜异位症之间的乘性交互作用（P int =0.01）。结论：这些发现提示卵巢肿瘤发生受到很大程度上独立作用的促炎和抗炎通路的强烈塑造。进一步考察这些通路可能阐明组织学类型异质性的起源并指导预防策略。

查看英文原文 English abstract

Background: Chronic inflammation is implicated in ovarian carcinogenesis, but how different inflammation-related exposures individually or jointly affect histotype-specific associations remains unclear. Materials and Methods: We pooled data from 16 case-control studies in the Ovarian Cancer Association Consortium to evaluate associations of eight inflammation-related factors (anti-inflammatory: aspirin use, tubal ligation (TL); pro-inflammatory: endometriosis, obesity, lifetime ovulatory cycles (LOC), smoking, pelvic inflammatory disease (PID), polycystic ovary syndrome (PCOS)) with epithelial ovarian cancer (OvC) by histologic subtype. We examined individual associations and clustering of risk factors across histotypes and computed population attributable risk (PAR) for each factor. We assessed additive and multiplicative interactions for exposure combinations. Results: Associations with OvC risk differed by histotype (e.g., high-grade serous: aspirin: OR=0.90; 95%CI 0.82, 0.99; TL: OR=0.80; 95%CI 0.73, 0.88; overall serous: endometriosis: OR=1.17; 95%CI 1.03, 1.31; high LOC: OR=1.42; 95%CI 1.28, 1.58; obesity (low-grade serous): OR=1.50; 95%CI 1.14, 1.98). Clustering analyses showed highly correlated risk profiles in endometrioid and clear cell (r=0.91). High-grade serous and mucinous profiles were moderately correlated with endometrioid and clear cell (r=0.60) tumors. The profile for low-grade serous (r=0.36) tumors was distinct from other histotypes. PAR estimates suggested modifying aspirin use, TL, and LOCs could substantially reduce burdens of endometrioid, clear cell and mucinous tumors. Out of 28 exposure combinations tested in overall OvC and 189 by histotype, we observed 12 interactions. Not using aspirin regularly showed positive additive interactions with obesity and high LOCs, particularly in endometrioid tumors (obesity relative excess risk due to interaction (RERI)=0.74, 95%CI 0.31, 1.18; P int =0.001 for; LOCs RERI=0.80, 95%CI 0.03, 1.56; P int =0.04). Not using aspirin regularly also showed a positive additive interaction with endometriosis in clear cell tumors (RERI=1.77, 95%CI 0.03, 3.52; P int =0.05). Lack of TL showed positive interactions with obesity in endometrioid (RERI=0.86, 95%CI 0.17, 1.53; P int =0.01) and mucinous (RERI=1.10, 95%CI 0.23, 1.97; P int =0.01) tumors, while negative additive interactions were observed for smoking and endometriosis in endometrioid tumors (RERI=-1.12, 95%CI -2.19, -0.05; P int =0.04). A multiplicative interaction was observed between obesity and endometriosis in mucinous tumors (P int =0.01). Conclusion: The findings suggest ovarian tumorigenesis is strongly shaped by pro- and anti-inflammatory pathways that act largely independently. Further examining these pathways may clarify the origins of histotype heterogeneity and guide prevention strategies.

利益披露 Disclosure

M. Akonde, None.. S. Tworoger, None.. A. Jensen, None.. J. Sampson, None.. H. Anton-Culver, None.. D. Bowtell, None.. D. W. Cramer, None.. L. S. Cook, None.. J. A. Doherty, None.. S. K. Kjaer, None.. N. Le, None.. F. Modugno, None.. M. A. Rossing, None.. J. M. Schildkrau, None.. R. Sutphen, None.. D. Van Den Berg, None.. A. Wu, None.. A. Ziogas, None.

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