Moss Haley A, Samimi Goli, Havrilesky Laura J, Sherman Mark E, Myers Evan R
Duke University Medical Center, Durham, NC, USA.
Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
Genet Epidemiol. 2018 Feb;42(1):117-122. doi: 10.1002/gepi.22095. Epub 2017 Nov 30.
U.S. guidelines recommend BRCA1/2 mutation testing for women diagnosed with high-grade ovarian cancer (HGOC) to increase recognition of carriers, but most remain unidentified and at risk. Accordingly, an approach termed "Traceback" has been proposed in which probands are retrospectively identified by testing archived pathology specimens, and family members are traced to provide genetic counseling and testing. We used population-based data to estimate the number of family members who might be contacted through such a program. We used incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the number of women diagnosed with HGOC from 2005 to 2016, and census data to estimate the number of spouses, offspring, and siblings (both sexes). Using overall survival for HGOC from SEER and all-cause mortality rates from the Centers for Diseases Control and Prevention, we estimated the number of patients, spouses, offspring, and siblings of HGOC cases living in 2017. Due to the high mortality rate of HGOC, consent from living probands may be possible in only 42% of the cases; consent to test pathology specimens would need to be sought from next of kin for the remainder. In 2017, an estimated 406,919 living next of kin (spouses, siblings, offspring) would be available for potential consent. Testing archived ovarian cancer pathology specimens may enable the identification of BRCA1/2 mutation carriers, but consent from next of kin would be required in in 58% of cases. Although Traceback offers the possibility of identifying unaffected BRCA1/2 mutation carriers, pilot feasibility studies that include assessment of methods to secure consent are needed.
美国指南建议对被诊断为高级别卵巢癌（HGOC）的女性进行BRCA1/2基因突变检测，以提高对携带者的识别率，但大多数携带者仍未被识别且处于风险中。因此，有人提出了一种名为“回溯”的方法，即通过检测存档的病理标本回顾性地识别先证者，并追踪家庭成员以提供遗传咨询和检测。我们使用基于人群的数据来估计通过这样一个项目可能联系到的家庭成员数量。我们使用监测、流行病学和最终结果（SEER）项目的发病率数据来估计2005年至2016年被诊断为HGOC的女性数量，并使用人口普查数据来估计配偶、子女和兄弟姐妹（男女皆有）的数量。利用SEER中HGOC的总生存率和疾病控制与预防中心的全因死亡率，我们估计了2017年HGOC病例的患者、配偶、子女和兄弟姐妹的数量。由于HGOC的高死亡率，只有42%的病例可能获得在世先证者的同意；其余病例需要向近亲寻求同意以检测病理标本。2017年，估计有406,919名在世的近亲（配偶、兄弟姐妹、子女）可能会同意接受检测。检测存档的卵巢癌病理标本可能有助于识别BRCA1/2基因突变携带者，但58%的病例需要获得近亲的同意。尽管回溯法提供了识别未受影响的BRCA1/2基因突变携带者的可能性，但仍需要进行试点可行性研究，包括评估获取同意的方法。
