Ovarian cancer risk of Chinese women with BRCA1/2 germline pathogenic variants
Ovarian cancer risk of Chinese women with BRCA1/2 germline pathogenic variants
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DOI：
10.1038/s10038-022-01065-6
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发表时间：
2022-07
影响因子：
3.5
通讯作者：
L. Yao;Jie Sun;L. Hu;Jiuan-Nan Chen;Juan Zhang;Ye Xu;Yuntao Xie
中科院分区：
文献类型：
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作者：
L. Yao;Jie Sun;L. Hu;Jiuan-Nan Chen;Juan Zhang;Ye Xu;Yuntao Xie
评估BRCA 1/2生殖系致病性变异（PV）携带者发生卵巢癌的终生风险对BRCA 1/2携带者的临床管理具有重要意义。该队列研究招募了9903例BRCA 1/2状态确定的中国乳腺癌患者。其中，3984名先证者完成了家族史问卷，调查了他们亲属的健康状况，其中包括11,997名女性一级亲属。采用Kin-cohort方法，利用先证者一级女性亲属的卵巢癌病史估计BRCA 1/2生殖系致病性携带者患卵巢癌的风险。在3984例先证者中，126例（3.2%）携带BRCA 1 PV，183例（4.6%）携带BRCA 2 PV。70岁时BRCA 1携带者、BRCA 2携带者和非携带者患卵巢癌的估计累积风险分别为15.3%（95%CI 8.4-18.6%）、5.5%（95%CI 2.0-10.2%）和0.4%（95%CI 0.3-0.7%）。BRCA 1和BRCA 2携带者在40岁之前患卵巢癌的累积风险非常低，并且在45岁之前呈上升趋势。BRCA 1携带者患卵巢癌的累积风险大约是BRCA 2携带者的3倍，BRCA 1和BRCA 2携带者患卵巢癌的风险分别是非BRCA携带者的38倍和14倍。研究结果表明，BRCA 1/2 PV携带者在其一生中患卵巢癌的风险很高，尤其是BRCA 1携带者。这些结果有助于设计降低BRCA 1/2携带者卵巢癌风险的最佳策略。
Estimating the lifetime risk of ovarian cancer in Chinese women withBRCA1/2germline pathogenic variants (PVs) is of great importance for the clinical management ofBRCA1/2carriers. This cohort study recruited 9903 unselected Chinese breast cancer patients whoseBRCA1/2status was determined. Of these, 3984 probands completed family history questionnaires, which investigated the health status of their relatives, including 11,997 female first-degree relatives. The ovarian cancer risk ofBRCA1/2germline pathogenic carriers was estimated using the ovarian cancer history of proband first-degree female relatives via the Kin-cohort method. Of the 3984 probands, 126 (3.2%) carriedBRCA1PVs, and 183 (4.6%) carriedBRCA2PVs. The estimated cumulative risks of ovarian cancer by age 70 were 15.3% (95% CI 8.4–18.6%) forBRCA1carriers, 5.5% (95% CI 2.0–10.2%) forBRCA2carriers, and 0.4% (95% CI 0.3–0.7%) for noncarriers. The cumulative risks of ovarian cancer were very low before the age of 40 for bothBRCA1andBRCA2carriers and were an increase up to age 45. The cumulative ovarian cancer risk ofBRCA1carriers was approximately three times higher than that ofBRCA2carriers, andBRCA1andBRCA2carriers had 38- and 14-fold higher risks than non-BRCAcarriers, respectively. The findings indicate that Chinese women withBRCA1/2PVs have high risks of ovarian cancer in their lifetime, especiallyBRCA1carriers. These results are useful for devising optimal strategies to reduce ovarian cancer risk inBRCA1/2carriers.