PDF(Pubmed)
Abstract：
UNASSIGNED: Although hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations.
UNASSIGNED: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the \"Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults\" of the University-Hospital Policlinico \"P. Giaccone\" of Palermo (Italy).
UNASSIGNED: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing.
UNASSIGNED: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.
UNASSIGNED: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the \"Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults\" of the University-Hospital Policlinico \"P. Giaccone\" of Palermo (Italy).
UNASSIGNED: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing.
UNASSIGNED: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.
摘要：
■虽然遗传性男性肿瘤相当罕见,携带种系BRCA1/2致病变异（PVs）的个体可能有发展与遗传性乳腺癌和卵巢癌（HBOC）综合征相关的肿瘤的风险，包括男性乳房（MBC），前列腺癌（PCa）和胰腺癌（PC），还有黑色素瘤.女性和男性表现出相当的癌症易感性遗传结构，但是有一些特定的性别特征。由于对男性人群的癌症遗传易感性知之甚少，我们的研究旨在调查男性HBOC综合征相关肿瘤患者BRCA1/2PVs的发生率，为了了解性别差异是否可以反映种系改变的患病率和范围。
我们回顾性地收集并分析了352名HBOC相关男性癌症患者的临床信息，这些患者通过下一代测序分析进行了种系BRCA1/2PV基因测试，已注册,从2018年2月到2024年1月，在“区域预防中心”，成人“大学医院Policlinico”P的罕见和遗传性家族性肿瘤的诊断和治疗巴勒莫（意大利）的Giaccone\“。
■我们的调查显示，7.4%的患者是种系BRCAPV的携带者，几乎完全流行的BRCA2改变。特别是,65.4%的BRCA阳性患者发生MBC,19.2%拥有PC，11.6%开发了PCa，只有3.8%有黑色素瘤。具体来说,MBC个体在17％的病例中表现出BRCA相关的遗传易感性，而PCa或PC患者的BRCA2PVs频率较低，考虑到目前国家进入种系基因检测的标准。
■我们的研究表明男性中生殖系BRCA2PV的患病率具有高度异质性，这可能反映出潜在的性别特异性遗传异质性。因此,BRCA相关的男性肿瘤可能是由于BRCA2PV与通常在女性中检测到的不同。如果它被证明，在未来,男性癌症在基因上与女性癌症不同，这可以改善个性化的风险评估，并指导男女患者的治疗选择，为了在癌症治疗中获得性别平等。
我们回顾性地收集并分析了352名HBOC相关男性癌症患者的临床信息，这些患者通过下一代测序分析进行了种系BRCA1/2PV基因测试，已注册,从2018年2月到2024年1月，在“区域预防中心”，成人“大学医院Policlinico”P的罕见和遗传性家族性肿瘤的诊断和治疗巴勒莫（意大利）的Giaccone\“。
■我们的调查显示，7.4%的患者是种系BRCAPV的携带者，几乎完全流行的BRCA2改变。特别是,65.4%的BRCA阳性患者发生MBC,19.2%拥有PC，11.6%开发了PCa，只有3.8%有黑色素瘤。具体来说,MBC个体在17％的病例中表现出BRCA相关的遗传易感性，而PCa或PC患者的BRCA2PVs频率较低，考虑到目前国家进入种系基因检测的标准。
■我们的研究表明男性中生殖系BRCA2PV的患病率具有高度异质性，这可能反映出潜在的性别特异性遗传异质性。因此,BRCA相关的男性肿瘤可能是由于BRCA2PV与通常在女性中检测到的不同。如果它被证明，在未来,男性癌症在基因上与女性癌症不同，这可以改善个性化的风险评估，并指导男女患者的治疗选择，为了在癌症治疗中获得性别平等。
