PO.PS01.08 · 人群科学

对常见癌症易感基因的靶向测序揭示非洲前列腺癌患者中的种系变异

Targeted sequencing of common cancer susceptibility genes reveals germline variants in African prostate cancer patients

编号 6289 展板 19 时间 4/21 02:00–05:00 区域 Section 34 主讲 Solomon Rotimi, PhD

分会场 Genetic Epidemiology 2: Pathway Analysis, Sequencing, Functional Genetics / Family and Hereditary Studies

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作者与单位 Authors & Affiliations

Abimbola F. Onyia¹, Freeman Okwuchi¹, Opeyemi C. De Campos¹, Sylvester Divine¹, Olutola Olasehinde¹, Ayinde Yahaya², Ayo Salako³, Aminu Zakari⁴, Iya Bassey⁵, Nicholas Titiloye⁶, Bernard Petershie⁶, Isidore GANDAHO⁷, Luc Brun⁷, Tore Sanni⁷, Safiatou Coulibaly⁸, Noel Coulibaly⁹, Michael Fakayode⁸, Coulibaly Issoufou¹⁰, Valérie Gbonon⁸, Kouame Benjamin¹⁰, Yao Evrard⁹, Peter Coleman¹¹, Ayun Cassell¹¹, Victor Ajumbo¹², Lilac Wattanga¹³, Benson Ochieng Nyambega¹², Folakemi T. Odedina¹⁴, Solomon Rotimi¹

¹Covenant University, Ota, Ogun State, Nigeria,²iCCaRE for Black Men Consortium, Ogun, Nigeria,³Obafemi Awolowo Teaching Hospital Complex, Ile Ife, Osun State, Nigeria,⁴Aminu Kano Teaching Hospital, Kano, Nigeria,⁵University of Calabar Teaching Hospital, Calabar, Nigeria,⁶Kwame Nkrumah University of Science and Technology, Kumasi, Ghana,⁷Parakou Teaching Hospital, Parakou, Benin,⁸Pasteur Institute of Cote d'Ivoire, Abidjan, Côte D'Ivoire,⁹Teaching Hospital of Treichville, Abidjan, Côte D'Ivoire,¹⁰Teaching Hospital of Cocody, Abidjan, Côte D'Ivoire,¹¹John F. Kennedy Memorial Hospital, Monrovia, Liberia,¹²Maseno University, Maseno, Kenya,¹³Jaramogi Oginga Odinga Teaching & Referral Hospital, Kisumu, Kenya,¹⁴Mayo Clinic Florida, Jacksonville, FL

摘要 Abstract

中文摘要

背景：前列腺癌（PCa）是全球癌症相关死亡的首要原因，并不成比例地影响非洲裔男性。非洲男性往往在更年轻的年龄发病且疾病更具侵袭性，约一半的 PCa 风险归因于遗传因素。非洲是世界上基因最多样化的地区，即使在非洲大陆内部，各人群在等位基因频率和致病性变异模式上也表现出重要差异。尽管存在这种多样性，非洲男性在基因组研究中仍然代表性不足，造成了限制精准医学努力的重大知识空白。方法：共从贝宁、科特迪瓦、加纳、肯尼亚和尼日利亚的教学医院招募了 182 名前列腺癌患者。使用 Aviseq ONCO50 组套和 Illumina MiSeq 平台对 50 个癌症易感基因进行测序。使用内部 Snakemake 工作流程进行变异识别，随后进行额外的生物信息学步骤，以区分真正的 PMS2 变异与 PMS2CL 相关的假象。致病性评估依赖于 ClinVar 和 LOVD 数据库的注释。结果：在研究组中 31.3% 的患者检测到致病性和可能致病性变异，涉及 26 个基因。五个最常发生改变的基因为 RAD50、PTCH1、MSH6、MUTYH 和 NF1。尼日利亚患者占所有致病性变异的 52.6%，其中在 MSH6、MUTYH、NF1 和 PTCH1 中观察到复发性改变。相比之下，致病性 BRCA1 和 BRCA2 变异主要在来自肯尼亚、贝宁和科特迪瓦的患者中观察到。本研究鉴定的若干移码、无义和剪接位点变异此前尚未在非洲人群中报道。结论：本研究提供了对非洲 PCa 患者遗传性癌症易感基因变异的最详细评估之一。研究结果揭示了致病性变异谱中存在显著的区域差异，并突显了可能导致非洲裔男性 PCa 负担不均的人群特异性基因组特征。这些数据强调了在非洲内部扩大基因组研究工作以加强精准肿瘤学并减少全球 PCa 差异的重要性。

查看英文原文 English abstract

Background : Prostate cancer (PCa) is the leading cause of cancer-related deaths globally and disproportionately affects men of African ancestry. African men often present at younger ages and with more aggressive disease, and approximately half of the PCa risk has been attributed to genetic factors. Africa is the most genetically diverse region of the world, and even within the continent, populations show important differences in allele frequencies and patterns of pathogenic variation. Despite this diversity, African men remain underrepresented in genomic studies, creating significant gaps in knowledge that limit precision medicine efforts. Methods: A total of 182 prostate cancer patients were recruited from teaching hospitals in Benin, Côte d'Ivoire, Ghana, Kenya and Nigeria. 50 cancer susceptibility genes using the Aviseq ONCO50 panel and the Illumina MiSeq platform. Variant calling was performed using an in-house Snakemake workflow, followed by additional bioinformatic steps to distinguish true PMS2 variants from PMS2CL-related artifacts. Pathogenicity assessment relied on annotations from ClinVar and LOVD databases. Results: Pathogenic and likely pathogenic variants were detected in 31.3% of the study group identified in 26 genes. The five most frequently altered genes were RAD50, PTCH1, MSH6, MUTYH, and NF1. Nigerian patients accounted for 52.6 percent of all pathogenic variants, with recurrent alterations observed in MSH6, MUTYH, NF1, and PTCH1. In contrast, pathogenic BRCA1 and BRCA2 variants were observed primarily in patients from Kenya, Benin, and Côte d'Ivoire. Several frameshift, nonsense, and splice-site variants identified in this study have not been previously reported in African populations.[SR1] Conclusion: This study provides one of the most detailed assessments of inherited cancer susceptibility gene variants in African PCa patients. The findings reveal substantial regional variation in the spectrum of pathogenic variants and highlight population-specific genomic signatures that may contribute to the unequal burden of PCa in men of African ancestry. These data emphasize the importance of expanding genomic research efforts within Africa to strengthen precision oncology and reduce global PCa disparities.

利益披露 Disclosure

A. F. Onyia, None.. F. Okwuchi, None.. O. C. De Campos, None.. S. Divine, None.. O. Olasehinde, None.. A. Yahaya, None.. A. Salako, None.. A. Zakari, None.. I. Bassey, None.. N. Titiloye, None.. B. Petershie, None.. I. Gandaho, None.. L. Brun, None.. T. Sanni, None.. S. Coulibaly, None.. N. Coulibaly, None.. M. Fakayode, None.. C. Issoufou, None.. V. Gbonon, None.. K. Benjamin, None.. Y. Evrard, None.. P. Coleman, None.. A. Cassell, None.. V. Ajumbo, None.. L. Wattanga, None.. B. O. Nyambega, None.. S. Rotimi, None.

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