Rayan Nikkilä, Antti Mäkitie, Heikki Joensuu, Saara Markkanen, Klaus Elenius, Outi Monni, Aarno Palotie, Elmo Saarentaus, Tuula Salo, Argyro Bizaki-Vallaskangas
{"title":"与口腔舌鳞状细胞癌相关的新型遗传风险变异。","authors":"Rayan Nikkilä, Antti Mäkitie, Heikki Joensuu, Saara Markkanen, Klaus Elenius, Outi Monni, Aarno Palotie, Elmo Saarentaus, Tuula Salo, Argyro Bizaki-Vallaskangas","doi":"10.1007/s12105-025-01784-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC.</p><p><strong>Methods: </strong>A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers.</p><p><strong>Results: </strong>GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10-8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10<sup>-7</sup>), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10<sup>-11</sup>). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10<sup>-5</sup>).</p><p><strong>Conclusion: </strong>The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"45"},"PeriodicalIF":3.2000,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031715/pdf/","citationCount":"0","resultStr":"{\"title\":\"Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma.\",\"authors\":\"Rayan Nikkilä, Antti Mäkitie, Heikki Joensuu, Saara Markkanen, Klaus Elenius, Outi Monni, Aarno Palotie, Elmo Saarentaus, Tuula Salo, Argyro Bizaki-Vallaskangas\",\"doi\":\"10.1007/s12105-025-01784-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC.</p><p><strong>Methods: </strong>A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers.</p><p><strong>Results: </strong>GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10-8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10<sup>-7</sup>), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10<sup>-11</sup>). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10<sup>-5</sup>).</p><p><strong>Conclusion: </strong>The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC.</p>\",\"PeriodicalId\":47972,\"journal\":{\"name\":\"Head & Neck Pathology\",\"volume\":\"19 1\",\"pages\":\"45\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031715/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Head & Neck Pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s12105-025-01784-0\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Head & Neck Pathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s12105-025-01784-0","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：针对口腔舌鳞癌（OTSCC）的全基因组关联研究（GWAS）数据有限。本研究旨在探讨OTSCC的遗传关联。方法：采用FinnGen Data Freeze-12数据集对376例OTSCC进行GWAS分析。病例队列包括205名男性和171名女性。涉及舌底或舌扁桃体的恶性肿瘤被排除在病例队列之外。无恶性肿瘤病史的个体作为对照（n = 407,067）。一项全现象关联研究（PheWAS）对主要变异进行了评估，以评估它们与其他癌症的共同关联。结果：GWAS分析确定了三个与OTSCC （p -7）和脂溢性角化病相关的全基因组显著位点（OR = 1.11, p = 1.51 × 10-11）。与黑色素瘤存在共向效应（OR = 0.93, p = 6.24 × 10-5）。结论：GWAS检测到两种新的与OTSCC的遗传关联。需要进一步的研究来确定这些位点上的基因与OTSCC的分子发病机制有关。
Purpose: Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC.
Methods: A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers.
Results: GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10-8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10-7), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10-11). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10-5).
Conclusion: The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC.
期刊介绍：
Head & Neck Pathology presents scholarly papers, reviews and symposia that cover the spectrum of human surgical pathology within the anatomic zones of the oral cavity, sinonasal tract, larynx, hypopharynx, salivary gland, ear and temporal bone, and neck.
The journal publishes rapid developments in new diagnostic criteria, intraoperative consultation, immunohistochemical studies, molecular techniques, genetic analyses, diagnostic aids, experimental pathology, cytology, radiographic imaging, and application of uniform terminology to allow practitioners to continue to maintain and expand their knowledge in the subspecialty of head and neck pathology. Coverage of practical application to daily clinical practice is supported with proceedings and symposia from international societies and academies devoted to this field.
Single-blind peer review
The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
