Saporito Donika, Brock Pamela, Hampel Heather, Sipos Jennifer, Fernandez Soledad, Liyanarachchi Sandya, de la Chapelle Albert, Nagy Rebecca
Department of Clinical Cancer Genetics, MD Anderson Cancer Center, 1155 Pressler Street CPB5.3535, Houston, TX, 77030, USA.
Division of Human Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Fam Cancer. 2018 Jul;17(3):431-434. doi: 10.1007/s10689-017-0048-0.
Familial non-medullary thyroid cancer (FNMTC) is clinically defined as two or more first-degree relatives with NMTC and appears to follow an autosomal dominant inheritance pattern. Approximately 5-7% of NMTC is hereditary and affects multiple generations with a young age of onset. The primary aim of this study was to determine the age-specific penetrance of NMTC in individuals from a large family with FNMTC with a previously identified private mutation at 4q32, with a secondary aim to determine the penetrance for benign thyroid disease in this family. We present a large family with NMTC in which we had previously described a culpable mutation. Participants provided their personal medical history and family history. The germline 4q32 A > C mutation was detected in 34 of 68 tested individuals. Age-specific penetrance of thyroid cancer and benign thyroid disease was determined using the inverted Kaplan-Meier method of segregation analysis. Individuals who tested positive for the 4q32 mutation have a 68.9% (95% CI 46.5-88.7) risk of developing thyroid cancer by age 70 and a 65.3% (95% CI 46.0-83.8) risk of developing benign thyroid disease by age 70. The 4q32 A > C mutation significantly increases the risk to develop thyroid cancer but not benign thyroid disease in members of this family. The female:male sex ratio of 1.33 that we observed in affected mutation carriers differs greatly from the ratio of approximately 3:1 observed in PTC, supporting a central role of the mutation. Early thyroid surveillance with annual ultrasound is recommended to individuals testing positive for this private familial mutation.
家族性非髓样甲状腺癌（FNMTC）在临床上定义为两个或更多患有非髓样甲状腺癌的一级亲属，并且似乎遵循常染色体显性遗传模式。大约5%-7%的非髓样甲状腺癌是遗传性的，会影响多代人，且发病年龄较轻。本研究的主要目的是确定来自一个患有FNMTC的大家庭且先前已鉴定出4q32处存在特定私人突变的个体中，非髓样甲状腺癌的年龄特异性外显率，次要目的是确定该家族中良性甲状腺疾病的外显率。我们展示了一个患有非髓样甲状腺癌的大家庭，我们之前已描述过其中的致病突变。参与者提供了他们的个人病史和家族史。在68名接受检测的个体中，有34人检测到种系4q32 A>C突变。使用反向Kaplan-Meier分离分析方法确定甲状腺癌和良性甲状腺疾病的年龄特异性外显率。检测到4q32突变呈阳性的个体在70岁时患甲状腺癌的风险为68.9%（95%可信区间46.5-88.7），在70岁时患良性甲状腺疾病的风险为65.3%（95%可信区间46.0-83.8）。4q32 A>C突变显著增加了该家族成员患甲状腺癌的风险，但未增加患良性甲状腺疾病的风险。我们在受影响的突变携带者中观察到的女性与男性比例为1.33，与在乳头状甲状腺癌中观察到的约3:1的比例有很大差异，这支持了该突变的核心作用。建议对检测到这种私人家族性突变呈阳性的个体每年进行超声检查以进行早期甲状腺监测。
