Onnekink A M, Klatte D C F, van Hooft J E, van den Berg S H, van der Zwaan S M S, van Doorn R, Hinnen S C H, Potjer T P, Bleiker E M A, van Leerdam M E
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA.
Fam Cancer. 2024 Aug;23(3):255-265. doi: 10.1007/s10689-024-00401-3. Epub 2024 Jun 1.
Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (at-risk carriers) using of a one-time questionnaire.A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46-63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22-32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children's cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options.
携带种系CDKN2A致病变异（PV）的个体一生中患黑色素瘤和胰腺癌的风险会大幅增加。这项横断面研究通过一次性问卷调查，评估了确诊的CDKN2A PV携带者以及有50% PV风险的个体（高危携带者）对基因检测、计划生育和植入前基因检测（PGT）的态度。总共筛选了537人是否符合条件，其中366名确诊携带者中有208人（57%）（56%为女性，中位年龄54岁[四分位间距46 - 63岁]），171名高危携带者中有39人（23%）（59%为女性，中位年龄26岁[四分位间距22 - 32岁]）参与了研究。基因检测的主要动机是控制自身和子女的癌症风险，以及加强癌症监测措施。相比之下，担心无法获得抵押贷款和人寿保险常被引述为推迟基因检测的原因。计划生育决策在确诊携带者和高危携带者中基本未受影响；然而，大多数确诊携带者在组建家庭时仍未意识到其家族或个人的癌症风险。超过60%的参与者不熟悉PGT，只有少数人（19%的确诊携带者和10%的高危携带者）愿意考虑将PGT作为一种生殖选择。本研究发现，受CDKN2A PV影响的个体对基因检测、计划生育和PGT的态度存在差异。了解这些不同态度有助于临床医生应对围绕这些问题的复杂性，特别是对于面临基因检测时机、计划生育以及辅助生殖选择潜在用途等艰难决策的年轻个体。
