编译：郑宝艳
来源：桓兴医讯
目的（Purpose）
卵巢癌病因异质性的探究对改善卵巢癌预防、早期诊断水平和治疗方法选择至关重要。在卵巢癌队列研究联盟中，我们围绕组织学亚型，评估了14项相关因素，包括激素、生育和生活方式。
An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).
患者和方法（Patients and Methods）
从21项研究中的130万名女性中，确定5584例浸润性上皮性卵巢癌患者（3378例浆液性、606例子宫内膜样、331例黏液性、269例透明细胞、其他1000例）。按21项研究和出生年份进行分层，对年龄、胎次、口服避孕药使用情况进行调校，采用竞争风险Cox比例风险回归模型分析，我们评价了与按组织学划分的所有浸润性卵巢癌的相关性。通过似然比检验进行异质性评价。
Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.
结果（Results）
按组织学划分，大多数危险因素表现出明显的异质性。较多的活产次数与子宫内膜样卵巢癌（每产次相对危险度[RR]0.78，95%CI，0.74至0.83）和透明细胞卵巢癌（RR，0.68；95%CI，0.61至0.76）相关性最强（对异质性的检验P值[P-het]<0.001）。同样，绝经年龄、子宫内膜异位症和输卵管结扎仅与子宫内膜样卵巢癌、透明细胞卵巢癌相关（P-het≤0.01）。乳腺癌家族史（P-het=0.008）有适度的异质性。吸烟与粘液性卵巢癌的风险增加相关（每20包-年的RR为1.26，95%CI，1.08到1.46）,但吸烟与透明细胞卵巢癌风险降低相关（RR，0.72；95%CI，0.55至0.94）（P-het=0.004）。按照危险因素进行无监督聚类分析，从高级别浆液性卵巢癌和粘液性卵巢癌中，区分出了子宫内膜样卵巢癌、透明细胞卵巢癌和低级别浆液性卵巢癌。
Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.
结论（Conclusion）
卵巢癌亚型与危险因素相关性的异质性表明，对卵巢癌亚型的病因学研究至关重要。大多数已知的危险因素与非浆液性卵巢癌有更强的相关性，表明对浆液性卵巢癌这一致命亚型的风险预测仍面临挑战。
The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
责任编辑：Dr.q
苏公网安备32059002004080号
