Therapeutic and Diagnostic Factors as Related to Cancer Risk

我们在这个项目中的大部分投资组合都集中在外源性激素对癌症风险的影响上。使用SEER数据的描述性分析记录了2002年妇女健康倡议(WHI)试验结果公布后子宫内膜癌发病率的增加。我们假设这反映了持续使用雌激素加孕激素(E+P)MHT的广泛减少(这种治疗与WHI内乳腺癌风险的增加有关)，因为我们和其他人已经证明，这一暴露导致超重和肥胖女性子宫内膜癌风险的降低。相反，在另一项分析中，我们发现长期连续使用E+P(涉及大量接触非对立雌激素)与风险增加相关；这种关联仅限于体重从瘦到正常的女性，可能反映了她们较低的内源性雌激素水平。在另一项专注于卵巢癌的研究中，我们发现连续和连续使用E+P都与卵巢癌风险增加有关。事实上，在一项描述性研究中，我们注意到，在WHI结果公布后，随着MHT使用的显著减少，50岁及50岁以上女性的卵巢癌发病率在年龄段队列模型中加速下降。肝癌发病率的显著性别差异表明，荷尔蒙影响风险，导致人们对使用MHT的影响感兴趣。然而，在肝癌汇集项目(LCPP)中，我们没有发现任何证据表明肝癌风险与使用MHT有关，尽管我们对所使用的特定类型的制剂的信息有限。除了MHT，我们还关注长期使用生育药物。在对我们的大量美国不孕症队列的长期随访中，我们没有发现克罗米芬的使用与卵巢癌或子宫内膜癌的关系。然而，接触12个或更多克罗米芬周期的妇女处于

A large part of our portfolio within this Project has focused on the effects on cancer risk of exogenous hormones. Descriptive analyses using data from SEER documented increases in endometrial cancer incidence after 2002 when results from the Womens Health Initiative (WHI) Trial were published. We hypothesized that this reflected widespread decreases in continuous estrogen plus progestin (E+P) MHT use (the therapy linked with increased breast cancer risk within WHI), given that this is an exposure that we as well as others have documented as leading to reductions in endometrial cancer risk in overweight and obese women. In contrast, in another analysis, we found long-term sequential E+P use (which involves substantial exposure to unopposed estrogens) is associated with increased risk; this association was restricted to thin-to-normal weight women, presumably reflecting their lower endogenous estrogen levels. In an additional investigation focused on ovarian cancer, we found that both sequential and continuous E+P usage was associated with ovarian cancer risk increases. In fact, in a descriptive study, we noted an accelerated decline in ovarian cancer incidence among women 50 years and older in age-period-cohort models following the marked reduction in MHT use that occurred after publication of the WHI results. The notable gender discrepancy in rates of liver cancer has suggested that hormones influence risk, leading to an interest in the effects of MHT use. However, in the Liver Cancer Pooling Project (LCPP), we found no evidence that liver cancer risk was related to MHT use, although we had limited information of the specific types of preparations used.In addition to MHT, we have also been concerned regarding the long-term use of fertility drugs. In an extended followup of our large U.S. infertility cohort, we saw no relationship of clomiphene use to either ovarian or endometrial cancers. However, women exposed to 12 or more clomiphene cycles were at an