Manuel Gentiluomo PhD, Chiara Corradi PhD, Laura Apadula MS, Annalisa Comandatore MD, Gaetano Lauri MD, Gemma Rossi MD, Giulia Peduzzi PhD, Stefano Crippa MD, PhD, Cosmeri Rizzato PhD, Massimo Falconi MD, PhD, Paolo Giorgio Arcidiacono MD PhD, Luca Morelli MD, PhD, Gabriele Capurso MD, PhD, Daniele Campa PhD
{"title":"一项全基因组关联研究确定了8个与导管内乳头状黏液性肿瘤向恶性进展相关的基因座。","authors":"Manuel Gentiluomo PhD, Chiara Corradi PhD, Laura Apadula MS, Annalisa Comandatore MD, Gaetano Lauri MD, Gemma Rossi MD, Giulia Peduzzi PhD, Stefano Crippa MD, PhD, Cosmeri Rizzato PhD, Massimo Falconi MD, PhD, Paolo Giorgio Arcidiacono MD PhD, Luca Morelli MD, PhD, Gabriele Capurso MD, PhD, Daniele Campa PhD","doi":"10.1002/cncr.35678","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome-wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed. A PHS was calculated using the genotypes of common variants associated with IPMN progression identified.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Eight loci with significant associations (<i>p</i> < 5 × 10<sup>−8</sup>) were identified, and the most significant was 7q21.11-rs117620617 (hazard ratio, 16.35; 95% confidence interval, 6.93–38.60; <i>p</i> = 1.80 × 10<sup>−10</sup>). All variants were associated with inflammatory processes, suggesting that alleles that predispose to an inflammatory prone phenotype may promote progression. The PHS indicated a statistically significant association (hazard ratio, 18.05; 95% confidence interval, 7.96–45.80; <i>p</i> = 6.18 × 10<sup>−11</sup>) with IPMN progression among individuals who had the highest number of effect alleles (fourth quartile) compared with those who had the lowest number (first quartile).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The current results study advance the understanding of individual predisposition to IPMN progression and underscore the potential use of genetics in the stratification of patients who have IPMN.</p>\n </section>\n </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 1","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694541/pdf/","citationCount":"0","resultStr":"{\"title\":\"A genome-wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy\",\"authors\":\"Manuel Gentiluomo PhD, Chiara Corradi PhD, Laura Apadula MS, Annalisa Comandatore MD, Gaetano Lauri MD, Gemma Rossi MD, Giulia Peduzzi PhD, Stefano Crippa MD, PhD, Cosmeri Rizzato PhD, Massimo Falconi MD, PhD, Paolo Giorgio Arcidiacono MD PhD, Luca Morelli MD, PhD, Gabriele Capurso MD, PhD, Daniele Campa PhD\",\"doi\":\"10.1002/cncr.35678\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome-wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed. A PHS was calculated using the genotypes of common variants associated with IPMN progression identified.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Eight loci with significant associations (<i>p</i> < 5 × 10<sup>−8</sup>) were identified, and the most significant was 7q21.11-rs117620617 (hazard ratio, 16.35; 95% confidence interval, 6.93–38.60; <i>p</i> = 1.80 × 10<sup>−10</sup>). All variants were associated with inflammatory processes, suggesting that alleles that predispose to an inflammatory prone phenotype may promote progression. The PHS indicated a statistically significant association (hazard ratio, 18.05; 95% confidence interval, 7.96–45.80; <i>p</i> = 6.18 × 10<sup>−11</sup>) with IPMN progression among individuals who had the highest number of effect alleles (fourth quartile) compared with those who had the lowest number (first quartile).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>The current results study advance the understanding of individual predisposition to IPMN progression and underscore the potential use of genetics in the stratification of patients who have IPMN.</p>\\n </section>\\n </div>\",\"PeriodicalId\":138,\"journal\":{\"name\":\"Cancer\",\"volume\":\"131 1\",\"pages\":\"\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-12-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694541/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cncr.35678\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cncr.35678","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
A genome-wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy
Background
Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome-wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN.
Methods
The study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed. A PHS was calculated using the genotypes of common variants associated with IPMN progression identified.
Results
Eight loci with significant associations (p < 5 × 10−8) were identified, and the most significant was 7q21.11-rs117620617 (hazard ratio, 16.35; 95% confidence interval, 6.93–38.60; p = 1.80 × 10−10). All variants were associated with inflammatory processes, suggesting that alleles that predispose to an inflammatory prone phenotype may promote progression. The PHS indicated a statistically significant association (hazard ratio, 18.05; 95% confidence interval, 7.96–45.80; p = 6.18 × 10−11) with IPMN progression among individuals who had the highest number of effect alleles (fourth quartile) compared with those who had the lowest number (first quartile).
Conclusions
The current results study advance the understanding of individual predisposition to IPMN progression and underscore the potential use of genetics in the stratification of patients who have IPMN.
期刊介绍：
The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society.
CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research
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