Type 1 and Type 2 Endometrial Cancer: Have They Different Risk Factors? A Pooled

简介（申请人提供）：子宫内膜癌是西方最常见的妇科恶性肿瘤。根据发病机制和临床结果的不同，子宫内膜癌被分为两种类型。1型肿瘤占子宫内膜癌的约90%，被归类为子宫内膜样腺癌。其余的2型子宫内膜癌主要是浆液性、透明细胞癌和鳞状细胞癌。被诊断为2型癌症的女性比被诊断为1型癌症的女性病情更严重，生存时间更短。据报道，不同的体细胞突变与子宫内膜癌的发展有关，这表明这两种肿瘤组可能具有不同的病因。目前，人们对2型癌症的危险因素几乎一无所知。由于2型癌症仅占子宫内膜癌的10%左右，因此联合研究是获得足够大的样本量来研究其风险因素的唯一方法。在这项研究中，我们对美国国家癌症研究所子宫内膜癌流行病学协会（E2C2）的24项流行病学研究（10项队列研究和14项病例对照研究）进行了汇总分析，以评估1型和2型子宫内膜癌危险因素的异同。具体来说，我们将研究月经特征、生殖因素、肥胖、外源性激素使用、吸烟、饮酒、医疗状况、子宫内膜癌和乳腺癌家族史与浸润性组织学证实的1型（n=13,000例）和2型（n=1,100例）子宫内膜癌之间的关系。汇集分析的大样本量有能力为子宫内膜癌危险因素的文献增加独特的信息。特别是，本研究有能力填补目前关于临床上侵袭性和致死性2型子宫内膜癌危险因素的知识空白。

DESCRIPTION (provided by applicant): Endometrial cancer is the most common gynecological malignancy in the Western world. Based on differences in pathogenesis and clinical outcomes, endometrial cancer has been divided into two types. Type 1 tumors account for ~90% of endometrial cancers and are classified as endometrioid adenocarcinoma. The remaining Type 2 endometrial cancers are predominantly serous, clear cell, and squamous cell carcinomas. Women diagnosed with type 2 cancers have aggressive disease and poorer survival than those diagnosed with type 1 cancers. Differing somatic mutations implicated in endometrial cancer development have been reported suggesting that the two tumor groups may have distinct etiologies. At present, almost nothing is known about risk factors for Type 2 cancers. Since Type 2 cancers represent only about 10% of endometrial cancers, combining studies is the only way to attain large enough sample sizes to study their risk factors. In this study, we propose a pooled analysis of 24 epidemiologic studies (10 cohort and 14 case-control studies) within the National Cancer Institute's Epidemiology of Endometrial Cancer Consortium (E2C2) to assess the similarities and differences in risk factors for Types 1 and 2 endometrial cancers. Specifically we will examine the associations of menstrual characteristics, reproductive factors, obesity, exogenous hormone use, smoking, alcohol drinking, medical conditions, and family history of endometrial and breast cancer with invasive histologically confirmed Type 1 (n=13,000 cases) and Type 2 (n=1,100) endometrial cancers. The large sample size of the pooled analysis has the power to add unique information to the literature on endometrial cancer risk factors. In particular, this study has the ability to fill the current void in the knowledge about risk factors for the clinically aggressive and lethal Type 2 endometrial cancers.