Erasmus MC Cancer Centre, Rotterdam, The Netherlands.
Netherlands Cancer Institute, Amsterdam, The Netherlands.
BMJ Open. 2024 Oct 9;14(10):e086688. doi: 10.1136/bmjopen-2024-086688.
c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis of breast cancer and other tumours in c.1100delC carriers is lacking. The nationwide HEreditary Breast and Ovarian cancer study the Netherlands (Hebon) cohort aims to answer study questions in families with an increased risk of breast cancer and ovarian cancer. While initially focusing on -variant families, Hebon gradually expanded to include pathogenic variants in other genes associated with breast and/or ovarian cancer over time. This provides an excellent setting to establish a cohort to ultimately study the impact of c.1100delC on cancer risk prediction and surveillance, breast cancer treatment and prognosis.
We invited all heterozygous and homozygous c.1100delC indexes and tested female relatives. 1802 women were included, of whom 1374 were heterozygotes and 938 were breast cancer cases. Pedigrees were collected from all clinical genetic departments. Furthermore, participants completed a detailed questionnaire on hormonal and lifestyle factors, family history, cancer diagnosis and treatment.
Mean age at study inclusion was 53 years. Linkage with the Netherlands Cancer Registry showed a younger age at diagnosis in homozygotes (mean age 41.7 years) and heterozygotes (47.9 years) than non-carriers (51.2 years). Furthermore, carriers were more often diagnosed with grade 2, oestrogen receptor-positive breast cancer and more often developed contralateral breast cancer than non-carriers. Most women consumed alcohol regularly and about half never smoked.
Further data linkages with the Netherlands Cancer Registry will allow prospective follow-up and breast cancer risk assessment in unaffected women at the time of genetic testing, risk of contralateral breast cancer and survival in patients with breast cancer. Also, linkage with the nationwide network and registry of histopathology and cytopathology in The Netherlands (PALGA) allows us to retrieve tumour samples to study tumourigenesis.
c.1100delC 与女性乳腺癌风险增加相关。虽然该变体在荷兰很常见（普通人群中的 1%），但缺乏对携带该变体的乳腺癌和其他肿瘤的病因学和预后的了解。荷兰全国遗传性乳腺癌和卵巢癌研究（Hebon）队列旨在回答具有乳腺癌和卵巢癌风险增加的家族中的研究问题。虽然最初专注于 -variant 家族，但随着时间的推移，Hebon 逐渐扩大到包括与乳腺癌和/或卵巢癌相关的其他基因的致病性变体。这为建立一个队列来最终研究 c.1100delC 对癌症风险预测和监测、乳腺癌治疗和预后的影响提供了极好的环境。
我们邀请了所有杂合子和纯合子 c.1100delC 索引携带者，并对女性亲属进行了检测。共纳入 1802 名女性，其中 1374 名为杂合子，938 名为乳腺癌患者。所有临床遗传科都收集了家系。此外，参与者还完成了关于激素和生活方式因素、家族史、癌症诊断和治疗的详细问卷。
研究纳入时的平均年龄为 53 岁。与荷兰癌症登记处的联系显示，纯合子（平均年龄 41.7 岁）和杂合子（47.9 岁）的诊断年龄比非携带者（51.2 岁）年轻。此外，携带者更常被诊断为 2 级、雌激素受体阳性乳腺癌，并且比非携带者更常发生对侧乳腺癌。大多数女性经常饮酒，约一半从不吸烟。
与荷兰癌症登记处的进一步数据联系将允许对遗传检测时未受影响的女性进行前瞻性随访和乳腺癌风险评估、对侧乳腺癌风险和乳腺癌患者的生存。此外，与荷兰全国组织病理学和细胞病理学网络和登记处（PALGA）的联系使我们能够检索肿瘤样本以研究肿瘤发生。
