Mapping the Prevalence of Lynch Syndrome in the Ceará-Northeast of Brazil.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Maria Claudia Dos Santos Luciano, Paulo Goberlanio de Barros Silva, Rosane Oliveira de Sant'Ana, Clarissa Gondim Picanço de Albuquerque, Francisca Fernanda Barbosa Oliveira, Flavio da Silveira Bitencourt, Isabelle Joyce de Lima Silva Fernandes, José Fernando Bastos Moura, Maria Júlia Barbosa Bezerra
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引用次数: 0

Abstract

Lynch syndrome (LS) is an autosomal dominant hereditary disorder that increases the risk of various cancers, especially colorectal (CRC) and endometrial cancer (EC). It results from pathogenic variants in mismatch repair (MMR) genes-primarily MLH1, MSH2, MSH6, and PMS2. Population-specific variant frequencies emphasize the need for localized genetic studies. Methods This study investigated LS prevalence in Ceará, Northeast Brazil, analyzing 150 patients: 130 with CRC, 13 with endometrial cancer, and 7 with other tumors but a family history of LS-associated cancers. Researchers used next-generation sequencing (NGS) to examine 131 genes linked to hereditary cancer syndromes. Variants were classified as Lynch-syndrome associated (MMR genes) or non-Lynch-associated (non-MMR genes). Detection rates varied from 1.18 to 5.07 per 100,000 people; pathogenic variant prevalence ranged from 0 to 1.96 per 100,000 across microregions. Overall, the prevalence of MMR variants was 0.56 per 100,000, and 0.34 for non-MMR variants. MSH2 showed the highest number of pathogenic or likely pathogenic variants, followed by MSH6, PMS2, and MLH1. The study found a particular geographic distribution of LS-related variants. One novel MSH6 variant and two unreported non-Lynch variants (APC and SMAD4) were identified. Conclusions These findings highlight three novel variants in MSH6, APC, and SMAD4, and indicate that Ceará has a higher diversity and a unique spectrum of variants. This reinforces the importance of regional genetic screening and suggests the need to expand testing access, especially in high-risk areas, to improve the early detection and prevention of hereditary cancers in Northeast Brazil.

绘制巴西Ceará-Northeast Lynch综合征患病率图。
Lynch综合征(LS)是一种常染色体显性遗传性疾病,可增加各种癌症的风险,特别是结直肠癌(CRC)和子宫内膜癌(EC)。它是由错配修复(MMR)基因的致病变异引起的,主要是MLH1、MSH2、MSH6和PMS2。群体特异性变异频率强调了本地化遗传研究的必要性。方法本研究调查了巴西东北部ceear地区的LS患病率,分析了150例患者,其中130例为结直肠癌,13例为子宫内膜癌,7例为其他肿瘤但有LS相关癌症家族史。研究人员使用下一代测序(NGS)检查了131个与遗传性癌症综合征相关的基因。变异被分类为Lynch-syndrome相关(MMR基因)或非Lynch-syndrome相关(non-MMR基因)。检出率从每10万人1.18到5.07不等;各微区致病变异的流行率从0到1.96 / 10万不等。总体而言,MMR变异的患病率为0.56 / 10万,非MMR变异的患病率为0.34 / 10万。MSH2的致病性或可能致病性变异最多,其次是MSH6、PMS2和MLH1。该研究发现了ls相关变异的特定地理分布。鉴定出一种新的MSH6变异和两种未报道的非lynch变异(APC和SMAD4)。这些发现突出了MSH6、APC和SMAD4的三个新变体,并表明ceear具有更高的多样性和独特的变体谱。这加强了区域遗传筛查的重要性,并表明需要扩大检测机会,特别是在高风险地区,以改善巴西东北部遗传性癌症的早期发现和预防。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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