Hormonal and reproductive risk factors for epithelial ovarian cancer by tumor aggressiveness.
Hormonal and reproductive risk factors for epithelial ovarian cancer by tumor aggressiveness.
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DOI：
10.1158/1055-9965.epi-12-1183-t
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
Tworoger SS
中科院分区：
文献类型：
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作者：
Poole EM;Merritt MA;Jordan SJ;Yang HP;Hankinson SE;Park Y;Rosner B;Webb PM;Cramer DW;Wentzensen N;Terry KL;Tworoger SS
大约一半的上皮性卵巢癌在三年内是致命的;然而，大约35%的妇女存活至少十年。在护士健康研究、新英格兰病例对照研究、澳大利亚卵巢癌研究和NIH-AARP饮食与健康研究中，我们通过肿瘤侵袭性（根据诊断至死亡的时间定义）调查了与卵巢癌危险因素相关性的潜在差异。我们使用考克斯比例风险竞争风险分析（NHS，AARP）或多分类逻辑回归（NECC，AOCS）计算已知或疑似卵巢癌危险因素与快速致死（诊断后3年内死亡）和侵袭性较低的肿瘤（所有其他）相关的相对风险（RR）和95%置信区间（CI）。使用随机效应荟萃分析将结果合并。与侵袭性较低的疾病相比，年龄的增加与快速致命的风险更大相关（OR，5年增加：1.39; 95%CI：1.29-1.49 vs. OR：1.09; 95%CI：1.03-1.16; p-diff<0.0001）。与侵袭性较低的疾病（OR：0.81; 95% CI：0.74-0.89; p-diff=0.002）相比，OC使用与快速致死性疾病风险的更大降低相关（OR，5年增加：0.69; 95% CI：0.58-0.82）。相反，增加产次仅与侵袭性较低的疾病相关（OR，每个孩子：0.87; 95%CI：0.81-0.93）。在对4，342例病例的分析中，快速致死性卵巢肿瘤与侵袭性较低的卵巢肿瘤的风险因素存在明显差异。肿瘤侵袭性的风险因素相关性的差异表明肿瘤发展的发展途径，并可能对制定最具侵袭性的癌症的一级预防策略很重要。
Approximately half of epithelial ovarian cancers are fatal within three years; however about 35% of women survive at least ten years. In the Nurses’ Health Study, New England Case-Control Study, Australian Ovarian Cancer Study, and NIH-AARP Diet and Health Study, we investigated potential differences in the associations with ovarian cancer risk factors by tumor aggressiveness, defined based on time from diagnosis until death. We calculated relative risks (RR) and 95% confidence intervals (CI) for associations of known or suspected ovarian cancer risk factors with rapidly fatal (death within three years of diagnosis) and less aggressive tumors (all others) using Cox proportional hazards competing risks analysis (NHS, AARP) or polytomous logistic regression (NECC, AOCS). Results were combined using random effects meta-analysis. Increasing age was associated with greater risk of rapidly fatal versus less aggressive disease (OR, 5-yr increase: 1.39; 95% CI: 1.29–1.49 vs. OR: 1.09; 95% CI: 1.03–1.16, respectively; p-diff<0.0001). OC use was associated with a greater decreased risk of rapidly fatal (OR, 5-yr increase: 0.69; 95% CI: 0.58–0.82) versus less aggressive disease (OR: 0.81; 95% CI: 0.74–0.89; p-diff=0.002). Conversely, increasing parity was associated only with less aggressive disease (OR, per child: 0.87; 95% CI: 0.81–0.93). In this analysis of 4,342 cases, there were clear differences in risk factors for rapidly fatal vs. less aggressive ovarian tumors. Differences in risk factor associations by tumor aggressiveness suggests the developmental pathways through which the tumors develop and may be important for developing primary prevention strategies for the most aggressive cancers.