DNA 损伤/修复基因变异与原发性卵巢功能不全 (POI) 和癌症风险相关。我们假设患有 POI 的女性和家庭成员的子集患癌症的风险会增加。使用 1995 年记录进行的基于人群的病例对照研究-2022 年。犹他州的两个主要学术医疗保健系统为该州 85% 的地区提供服务。使用 ICD 代码识别患有 POI 的女性 (n=613)，并审查其准确性。使用犹他州人口数据库将亲属联系起来。使用犹他州癌症登记处确定癌症诊断。通过与人口比率进行比较来估计 POI 女性和亲属患癌症的相对风险。对一部分女性进行了全基因组测序。患有 POI 的女性乳腺癌发病率增加（OR [95%CI] 2.20 [1.30, 3.47]；p=0.0023），并且卵巢癌名义上显着增加。 POI 先证者被诊断患有 POI 和癌症时分别为 36.5±4.3 岁和 59.5±12.7 岁。确定了癌症和 POI 的致病基因和候选基因变异。在这些女性的二级亲属中，患乳腺癌 (1.28 [1.08, 1.52]; p=0.0078) 和结肠癌 (1.50 [1.14, 1.94]) 的风险增加；p=0.0036)。一级亲属 (1.64 [1.18, 2.23]; p=0.0026)、二级亲属 (1.54 [1.32, 1.79]; p<0.001) 和三级亲属 (1.33 [1.20, 1.48]; p< 0.001)。数据表明 POI 和生殖系统癌症的常见遗传风险。需要工具来预测 POI 女性的癌症风险，并可能就激素替代疗法的风险提供咨询。© 作者 2024。由牛津大学出版社代表内分泌学会出版。

DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk.We hypothesized that a subset of women with POI and family members would have increased risk for cancer.Case-control population-based study using records from 1995-2022.Two major Utah academic healthcare systems serving 85% of the state.Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database.Cancer diagnoses were identified using the Utah Cancer Registry.The relative risk of cancer in women with POI and relatives was estimated by comparison to population rates. Whole genome sequencing was performed on a subset of women.Breast cancer was increased in women with POI (OR [95%CI] 2.20 [1.30, 3.47]; p=0.0023) and there was a nominally significant increase in ovarian cancer. Probands with POI were 36.5±4.3 years and 59.5±12.7 years when diagnosed with POI and cancer, respectively. Causal and candidate gene variants for cancer and POI were identified.Among second-degree relatives of these women, there was an increased risk of breast (1.28 [1.08, 1.52]; p=0.0078) and colon cancer (1.50 [1.14, 1.94]; p=0.0036). Prostate cancer was increased in first- (1.64 [1.18, 2.23]; p=0.0026), second- (1.54 [1.32, 1.79]; p<0.001), and third-degree relatives (1.33 [1.20, 1.48]; p<0.001).Data suggest common genetic risk for POI and reproductive cancers. Tools are needed to predict cancer risk in women with POI and potentially to counsel about risks of hormone replacement therapy.© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.