PDF(Pubmed)
Abstract：
BACKGROUND: Little is known about risks associated with germline SUFU pathogenic variants (PVs) known as a cancer predisposition syndrome.
METHODS: To study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germline SUFU PV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives with SUFU PV (89 patients) using the Nelson-Aalen estimator.
RESULTS: Overall, 117/172 (68%) SUFU PV carriers developed at least one tumour: medulloblastoma (MB) (86 patients), basal cell carcinoma (BCC) (25 patients), meningioma (20 patients) and gonadal tumours (11 patients). Thirty-three of them (28%) had multiple tumours. Median age at diagnosis of MB, gonadal tumour, first BCC and first meningioma were 1.5, 14, 40 and 44 years, respectively. Follow-up data were available for 160 patients (137 remained alive and 23 died). The cumulative incidence of tumours in relatives was 14.4% (95% CI 6.8 to 21.4), 18.2% (95% CI 9.7 to 25.9) and 44.1% (95% CI 29.7 to 55.5) at the age of 5, 20 and 50 years, respectively. The cumulative risk of an MB, gonadal tumour, BCC and meningioma at age 50 years was: 13.3% (95% CI 6 to 20.1), 4.6% (95% CI 0 to 9.7), 28.5% (95% CI 13.4 to 40.9) and 5.2% (95% CI 0 to 12), respectively. Sixty-four different PVs were reported across the entire SUFU gene and inherited in 73% of cases in which inheritance could be evaluated.
CONCLUSIONS: Germline SUFU PV carriers have a life-long increased risk of tumours with a spectrum dominated by MB before the age of 5, gonadal tumours during adolescence and BCC and meningioma in adulthood, justifying fine-tuned surveillance programmes.
METHODS: To study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germline SUFU PV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives with SUFU PV (89 patients) using the Nelson-Aalen estimator.
RESULTS: Overall, 117/172 (68%) SUFU PV carriers developed at least one tumour: medulloblastoma (MB) (86 patients), basal cell carcinoma (BCC) (25 patients), meningioma (20 patients) and gonadal tumours (11 patients). Thirty-three of them (28%) had multiple tumours. Median age at diagnosis of MB, gonadal tumour, first BCC and first meningioma were 1.5, 14, 40 and 44 years, respectively. Follow-up data were available for 160 patients (137 remained alive and 23 died). The cumulative incidence of tumours in relatives was 14.4% (95% CI 6.8 to 21.4), 18.2% (95% CI 9.7 to 25.9) and 44.1% (95% CI 29.7 to 55.5) at the age of 5, 20 and 50 years, respectively. The cumulative risk of an MB, gonadal tumour, BCC and meningioma at age 50 years was: 13.3% (95% CI 6 to 20.1), 4.6% (95% CI 0 to 9.7), 28.5% (95% CI 13.4 to 40.9) and 5.2% (95% CI 0 to 12), respectively. Sixty-four different PVs were reported across the entire SUFU gene and inherited in 73% of cases in which inheritance could be evaluated.
CONCLUSIONS: Germline SUFU PV carriers have a life-long increased risk of tumours with a spectrum dominated by MB before the age of 5, gonadal tumours during adolescence and BCC and meningioma in adulthood, justifying fine-tuned surveillance programmes.
摘要：
背景：关于与种系SUFU致病变异体（PV）相关的风险，已知为癌症易感综合征。
方法：为了研究肿瘤风险，我们分析了45例未发表的种系SUFUPV患者和127例以前发表的患者的大队列数据.为了减少由于索引患者选择而导致的确定偏差，使用Nelson-Aalen估计量对患有SUFUPV的亲属(89例患者)的肿瘤风险进行了评估.
结果：总体而言，117/172（68％）SUFUPV携带者至少发展了一种肿瘤：髓母细胞瘤（MB）（86例），基底细胞癌（BCC）（25例），脑膜瘤（20例）和性腺肿瘤（11例）。其中33例（28％）患有多个肿瘤。诊断MB时的中位年龄，性腺肿瘤，第一次BCC和第一次脑膜瘤分别为1.5年、14年、40年和44年，分别。可获得160例患者的随访数据（137例存活，23例死亡）。亲属中肿瘤的累积发病率为14.4%（95%CI6.8至21.4），在5、20和50岁时，分别为18.2%（95%CI9.7至25.9）和44.1%（95%CI29.7至55.5），分别。MB的累积风险，性腺肿瘤，50岁时的BCC和脑膜瘤为：13.3％（95％CI6至20.1），4.6%（95%CI0至9.7），28.5%(95%CI13.4至40.9)和5.2%(95%CI0至12)，分别。在整个SUFU基因中报告了64种不同的PV，并在73％的可以评估遗传的病例中遗传。
结论：生殖系SUFUPV携带者在5岁之前有一个以MB为主的肿瘤、青春期的性腺肿瘤和成年期的BCC和脑膜瘤的终生风险增加，为微调监测方案辩护。
方法：为了研究肿瘤风险，我们分析了45例未发表的种系SUFUPV患者和127例以前发表的患者的大队列数据.为了减少由于索引患者选择而导致的确定偏差，使用Nelson-Aalen估计量对患有SUFUPV的亲属(89例患者)的肿瘤风险进行了评估.
结果：总体而言，117/172（68％）SUFUPV携带者至少发展了一种肿瘤：髓母细胞瘤（MB）（86例），基底细胞癌（BCC）（25例），脑膜瘤（20例）和性腺肿瘤（11例）。其中33例（28％）患有多个肿瘤。诊断MB时的中位年龄，性腺肿瘤，第一次BCC和第一次脑膜瘤分别为1.5年、14年、40年和44年，分别。可获得160例患者的随访数据（137例存活，23例死亡）。亲属中肿瘤的累积发病率为14.4%（95%CI6.8至21.4），在5、20和50岁时，分别为18.2%（95%CI9.7至25.9）和44.1%（95%CI29.7至55.5），分别。MB的累积风险，性腺肿瘤，50岁时的BCC和脑膜瘤为：13.3％（95％CI6至20.1），4.6%（95%CI0至9.7），28.5%(95%CI13.4至40.9)和5.2%(95%CI0至12)，分别。在整个SUFU基因中报告了64种不同的PV，并在73％的可以评估遗传的病例中遗传。
结论：生殖系SUFUPV携带者在5岁之前有一个以MB为主的肿瘤、青春期的性腺肿瘤和成年期的BCC和脑膜瘤的终生风险增加，为微调监测方案辩护。
