Abstract：
BACKGROUND: DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk.
OBJECTIVE: We hypothesized that a subset of women with POI and family members would have increased risk for cancer.
METHODS: Case-control population-based study using records from 1995-2022.
METHODS: Two major Utah academic healthcare systems serving 85% of the state.
METHODS: Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database.
METHODS: Cancer diagnoses were identified using the Utah Cancer Registry.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
OBJECTIVE: We hypothesized that a subset of women with POI and family members would have increased risk for cancer.
METHODS: Case-control population-based study using records from 1995-2022.
METHODS: Two major Utah academic healthcare systems serving 85% of the state.
METHODS: Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database.
METHODS: Cancer diagnoses were identified using the Utah Cancer Registry.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：DNA损伤/修复基因变异与原发性卵巢功能不全（POI）和癌症风险有关。
目的：我们假设一部分患有POI的女性和家庭成员患癌症的风险会增加。
方法：使用1995-2022年记录的病例对照人群研究。
方法：两个主要的犹他州学术医疗保健系统服务于该州85％的地区。
方法：使用ICD编码对患有POI的女性（n=613）进行鉴定，并对准确性进行审查。亲戚使用犹他州人口数据库进行链接。
方法：使用犹他州癌症登记处确定癌症诊断。
方法：有POI和亲属的女性患癌症的相对风险是通过与人口比率比较来估计的。对一部分女性进行全基因组测序。
结果：患有POI的女性乳腺癌增加（OR[95CI]2.20[1.30,3.47];p=0.0023），卵巢癌名义上有显著增加。当被诊断为POI和癌症时，POI的前段分别为36.5±4.3年和59.5±12.7年。分别。鉴定了癌症和POI的原因和候选基因变体。在这些女性的二级亲属中，乳腺癌(1.28[1.08,1.52];p=0.0078)和结肠癌(1.50[1.14,1.94];p=0.0036)的风险增加.前列腺癌首先增加-（1.64[1.18,2.23];p=0.0026），第二-(1.54[1.32，1.79]；p<0.001)，和三级亲属(1.33[1.20，1.48]；p<0.001)。
结论：数据表明POI和生殖癌症的共同遗传风险。需要工具来预测患有POI的女性的癌症风险，并可能就激素替代疗法的风险提供咨询。
目的：我们假设一部分患有POI的女性和家庭成员患癌症的风险会增加。
方法：使用1995-2022年记录的病例对照人群研究。
方法：两个主要的犹他州学术医疗保健系统服务于该州85％的地区。
方法：使用ICD编码对患有POI的女性（n=613）进行鉴定，并对准确性进行审查。亲戚使用犹他州人口数据库进行链接。
方法：使用犹他州癌症登记处确定癌症诊断。
方法：有POI和亲属的女性患癌症的相对风险是通过与人口比率比较来估计的。对一部分女性进行全基因组测序。
结果：患有POI的女性乳腺癌增加（OR[95CI]2.20[1.30,3.47];p=0.0023），卵巢癌名义上有显著增加。当被诊断为POI和癌症时，POI的前段分别为36.5±4.3年和59.5±12.7年。分别。鉴定了癌症和POI的原因和候选基因变体。在这些女性的二级亲属中，乳腺癌(1.28[1.08,1.52];p=0.0078)和结肠癌(1.50[1.14,1.94];p=0.0036)的风险增加.前列腺癌首先增加-（1.64[1.18,2.23];p=0.0026），第二-(1.54[1.32，1.79]；p<0.001)，和三级亲属(1.33[1.20，1.48]；p<0.001)。
结论：数据表明POI和生殖癌症的共同遗传风险。需要工具来预测患有POI的女性的癌症风险，并可能就激素替代疗法的风险提供咨询。
