Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Milan, Italy; Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Hospital, San Raffaele Scientific Institute IRCCS, Milan, Italy.
Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Milan, Italy.
Pancreatology. 2020 Sep;20(6):1149-1154. doi: 10.1016/j.pan.2020.07.398. Epub 2020 Jul 31.
/Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women.
We conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher's exact tests where appropriate for categorical variables and Student's t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders.
253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91-0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30-0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15-0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38-0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC.
These data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.
/目的：与女性相比，男性中胰腺导管腺癌（PDAC）的发病率更高，尽管已知的危险因素差异并不能完全解释这种差异。临床前研究表明，生殖和激素因素会影响胰腺癌变，但关于该主题的少数已发表数据存在不一致。本研究旨在探讨生殖和激素因素对女性 PDAC 发生的作用。
我们进行了一项单中心病例对照研究；PDAC 病例按年龄与对照组以 1:2 的比例匹配。通过问卷调查妇科和病史来筛选危险因素。使用卡方检验和 Fisher 精确检验适用于分类变量，使用学生 t 检验适用于连续变量来进行比较。使用逻辑回归计算优势比（OR）及其 95%置信区间（CI）。多变量逻辑回归模型根据潜在混杂因素进行调整。
共纳入 253 例 PDAC 和 506 例匹配对照。多变量逻辑回归分析调整混杂因素后，绝经年龄较大（每增加 1 年，OR：0.95；95%CI：0.91-0.98；p=0.007）、使用口服避孕药（OR：0.52；95%CI：0.30-0.89；p=0.018）、使用激素替代疗法（OR：0.31；95%CI：0.15-0.64；p=0.001）和生育两个孩子（OR：0.57；95%CI：0.38-0.84；p=0.005）是 PDAC 发病的显著、独立保护因素。
这些数据证实了一些关于绝经年龄和生育次数的先前发现，同时，据我们所知，这是第一项表明 HRT 和 OC 使用具有保护作用的研究。这些结果共同支持了暴露于雌激素对 PDAC 具有保护作用的假说。
