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Abstract 2610: A high performance blood test for multiple cancer early screening 摘要2610:一种用于多种癌症早期筛查的高性能血液检测方法
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.am2021-2610
Linhao Xu, Jun Wang, Weifeng Ma, Xin Liu, Ting Yang, Sihui Li, Qian Hu, Jinsheng Tao, Z. Ye, Zhiwei Chen, Jian-Bing Fan
{"title":"Abstract 2610: A high performance blood test for multiple cancer early screening","authors":"Linhao Xu, Jun Wang, Weifeng Ma, Xin Liu, Ting Yang, Sihui Li, Qian Hu, Jinsheng Tao, Z. Ye, Zhiwei Chen, Jian-Bing Fan","doi":"10.1158/1538-7445.am2021-2610","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-2610","url":null,"abstract":"Introduction: Early detection is critical to improving cancer patient survival and quality of life. Cell-free DNA (cfDNA) methylation profiling is a promising diagnostic approach for early detection of cancer, even before symptoms appear. We previously reported a non-invasive and cost-effective methylation test, Aurora, which is able to detect three major cancer types with high specificity and sensitivity especially at early stages (I/II), including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC). We have improved this test to include two additional major cancer types, gastric cancer (GC) and esophageal cancer (EC). Taking together, these five cancer types represent 56% of new cancer cases and 60% of cancer-related deaths in China. Methods: We developed a novel high-throughput targeted methylation profiling platform, Aurora 2.0 (an improved version of Aurora 1.0, as presented in AACR 2020), to efficiently enrich and capture cancer-specific DNA methylation markers in plasma, prior to analysis via next-generation sequencing on a MiSeqDx system. About 100 cases each for GC and EC patients (mostly at Stage I/II), together with ~200 healthy controls, have been analyzed by using Aurora 2.0 and used for model development and validation. Results and Discussion: cfDNA methylation profiles have been obtained from 409 plasma samples, comprising 206 healthy controls, 98 GC and 105 EC patients. Logistic regression model has been developed with the Area Under Curve (AUC) of 94.0% and 93.5% for GC and EC, respectively. Overall, the performance (AUC) of Aurora 2.0 for LC/BC/CRC/GC/EC are 97.3%, 96.2%, 92%, 94% and 93.5%, respectively. An independent cohort (~2,000 plasma samples, five cancer types including lung, breast, colorectal, gastric and esophageal cancers with healthy controls) study is undergoing to further validate this test prospectively. The superior performance and cost-effectiveness (~$100) of the test could make early cancer screening of multiple major cancers in symptom-free and average-risk populations more achievable. Citation Format: Linhao Xu, Jun Wang, Weifeng Ma, Xin Liu, Ting Yang, Sihui Li, Qian Hu, Jinsheng Tao, Zhujia Ye, Zhiwei Chen, Jian-Bing Fan. A high performance blood test for multiple cancer early screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2610.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82237755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Abstract 2578: Calcium modulates apoptosis and differentiation in human normal colon 3D organoids irrespective of donor sex and biopsy site 摘要:钙可以调节人类正常结肠3D类器官的凋亡和分化,而不受供体性别和活检部位的影响
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2578
C. Dampier, M. Devall, J. Bryant, S. Eaton, J. Huyghe, Andre E Kim, Virginia Díez-Obrero, F. V. Duijnhoven, Duncan C. Thomas, S. Powell, W. Gauderman, U. Peters, G. Casey
{"title":"Abstract 2578: Calcium modulates apoptosis and differentiation in human normal colon 3D organoids irrespective of donor sex and biopsy site","authors":"C. Dampier, M. Devall, J. Bryant, S. Eaton, J. Huyghe, Andre E Kim, Virginia Díez-Obrero, F. V. Duijnhoven, Duncan C. Thomas, S. Powell, W. Gauderman, U. Peters, G. Casey","doi":"10.1158/1538-7445.AM2021-2578","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2578","url":null,"abstract":"Background: Observational studies indicate that calcium, a micronutrient involved in numerous cell-signaling cascades, may protect against colon cancer. Stratified analyses suggest the protective effect of calcium may depend on sex and anatomic subsite, but these hypotheses have been difficult to test experimentally. Here, we employ human-derived normal colon 3D organoids as a model of the healthy colon crypt to interrogate the effect of calcium exposure on gene expression and the effect of donor sex and biopsy anatomic subsite on the response to calcium. Methods: A total of 39 3D colon organoid lines derived from colon biopsies (22 proximal, 17 distal) obtained from unrelated subjects (21 female, 18 male) during screening colonoscopy were grown under low (1.7 mM) calcium conditions, and a matching set of the same lines were grown under high (5.0 mM) calcium conditions. After 72 hours, total RNA was extracted from organoid lines, libraries were prepared with poly-A selection, and bulk RNA-sequencing was used to measure gene expression. DNA was extracted from the same lines and genotyped using the OncoArray 500K beadchip. Missing genotypes were imputed to the TOPMed reference panel using the TOPMed Imputation Server. Polygenic risk scores for colorectal cancer were calculated for each organoid line using Plink and 135 of 141 genome-wide significant SNPs associated with colorectal cancer in recent genome-wide association studies. Relative expression between low and high calcium conditions was tested using generalized linear models as implemented in DESeq2. Functional enrichment of gene ontologies among differentially expressed genes was performed with ToppFun. The effects of donor sex, biopsy subsite, and organoid polygenic risk score on response to calcium were tested using single and multiple linear regression as implemented in the base R lm function. Results: Exposure to calcium induced differential expression of 767 genes with a false discovery rate of 5%. Differentially expressed genes were enriched for biological processes including extracellular structure organization (Bonferroni p=1.6E-3) and positive regulation of apoptosis (Bonferroni p=2.2E-2). Although stratified analyses demonstrated more differentially expressed genes in 3D colon organoids derived from male subjects, no statistically significant effect of sex, subsite, or polygenic risk score on response to calcium was observed. Conclusion: We tested the effect of calcium exposure on gene expression in human-derived normal colon 3D organoids and found that calcium modulated processes related to differentiation and apoptosis, but the response to calcium was not affected by sex, anatomic subsite, or polygenic risk score. Citation Format: Christopher H. Dampier, Matthew Devall, Jennifer Bryant, Stephen D. Eaton, Jeroen R. Huyghe, Andre E. Kim, Virginia Diez-Obrero, Franzel J. van Duijnhoven, Duncan C. Thomas, Steven M. Powell, W James Gauderman, Ulrike Peters, Graham Casey. Calcium modul","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85803613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 2521: Race specific differences in DNA damage repair dysregulation in breast cancer and association with outcome 摘要:乳腺癌DNA损伤修复失调的种族特异性差异及其与预后的关系
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2521
A. Mazumder, A. Jimenez, R. Ellsworth, S. Freedland, S. George, M. Bainbridge, S. Haricharan
{"title":"Abstract 2521: Race specific differences in DNA damage repair dysregulation in breast cancer and association with outcome","authors":"A. Mazumder, A. Jimenez, R. Ellsworth, S. Freedland, S. George, M. Bainbridge, S. Haricharan","doi":"10.1158/1538-7445.AM2021-2521","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2521","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76811698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 2568: Use of kinase inhibitors in Fanconi anemia oral cancercell lines 2568:激酶抑制剂在范可尼贫血口腔癌细胞系中的应用
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2568
W. N. Jungbauer, Mustafa M. Ali, B. Wuertz, F. Ondrey
{"title":"Abstract 2568: Use of kinase inhibitors in Fanconi anemia oral cancercell lines","authors":"W. N. Jungbauer, Mustafa M. Ali, B. Wuertz, F. Ondrey","doi":"10.1158/1538-7445.AM2021-2568","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2568","url":null,"abstract":"Successful Fanconi anemia (FA) treatment allows greater longevity for these patients. However, there is a greatly increased risk of squamous malignancies of the head and neck which are quite deadly in these young patients. There is an unmet need for non DNA damaging therapies for this malignancy which could augment surgery. Our approach has been to examine potential treatments based on known pathophysiology of the disease which would be acceptable for this population so we examined the effects of metformin and pioglitazone, as well as two cell cycle kinase inhibitors, in FA and leukoplakia cell lines. We examined dose-dependent and combination effects on cell proliferation, as judged by MTT assay. We examined metformin, pioglitazone, the polo-like kinase 1 inhibitor, GSK461364, and Wee1 kinase inhibitor, AZD1775.In single agent studies, we observed dose-dependent decreases in cell proliferation with all 4 single agents. We observed decreased cell proliferation in all cell lines at 72 hours at clinically achievable serum levels of 85% to 55% of control levels (P Citation Format: Walter N. Jungbauer, Mustafa M. Ali, Beverly R. Wuertz, Frank G. Ondrey. Use of kinase inhibitors in Fanconi anemia oral cancercell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2568.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"232 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77007414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Abstract 2548: Preclinical development of EARLI-001, a genetic platform producing cancer-activated synthetic biomarkers for the early detection of malignancies 摘要2548:early -001的临床前开发,early -001是一个产生癌症激活的合成生物标志物的遗传平台,用于早期检测恶性肿瘤
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2548
Badriprasad Ananthanarayanan, Regina Nieu, Evan Bishop, Shireen S. Rudina, A. Harwig, Bijee George, D. Suhy
{"title":"Abstract 2548: Preclinical development of EARLI-001, a genetic platform producing cancer-activated synthetic biomarkers for the early detection of malignancies","authors":"Badriprasad Ananthanarayanan, Regina Nieu, Evan Bishop, Shireen S. Rudina, A. Harwig, Bijee George, D. Suhy","doi":"10.1158/1538-7445.AM2021-2548","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2548","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77390556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Abstract 2531: Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort 摘要2531:bscc - medicare队列中老年妇女乳房x光筛查的功能相关指标和结果
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2531
Dongyu Zhang, L. Abraham, J. Demb, D. Miglioretti, S. Advani, B. Sprague, L. Henderson, Tracy Onega, K. Wernli, L. Walter, K. Kerlikowske, J. Schousboe, E. O'Meara, D. Braithwaite
{"title":"Abstract 2531: Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort","authors":"Dongyu Zhang, L. Abraham, J. Demb, D. Miglioretti, S. Advani, B. Sprague, L. Henderson, Tracy Onega, K. Wernli, L. Walter, K. Kerlikowske, J. Schousboe, E. O'Meara, D. Braithwaite","doi":"10.1158/1538-7445.AM2021-2531","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2531","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76871049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 2603: What's more in serrated lesions: interobserver agreement and molecular features 摘要2603:在锯齿状病变中更重要的是:观察者之间的一致和分子特征
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2603
F. Ambrosi, C. Ricci, Federico Chiarucci, Stefano Chilotti, Doriana Donatella Di Nanni, A. G. Corradini, Maria Antonietta Cumiento, D. Biase, M. Fiorentino
{"title":"Abstract 2603: What's more in serrated lesions: interobserver agreement and molecular features","authors":"F. Ambrosi, C. Ricci, Federico Chiarucci, Stefano Chilotti, Doriana Donatella Di Nanni, A. G. Corradini, Maria Antonietta Cumiento, D. Biase, M. Fiorentino","doi":"10.1158/1538-7445.AM2021-2603","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2603","url":null,"abstract":"Introduction: Serrated lesions are a heterogeneous group of lesions routinely evaluated with different morphologic subtypes, and colorectal carcinogenesis has been related to the understanding of the serrated pathway in these lesions. In this setting, BRAF V600E mutation has been demonstrated as a marker for the serrated carcinogenic evolution, while the mismatch repair protein (MMR) was recognized in a small subset of hyperplastic polyps. Design: This study aimed to evaluate the interobserver agreement among 6 pathologists in the morphological diagnosis of the serrated lesion according to WHO Classification; furthermore, the additional MMR (MLH1, PMS2, MSH2, MSH6) and BRAF V600E (VE1) mutation status were studied by immunohistochemistry and NGS analysis. Results: We evaluated 52 serrated lesions of the colon retrieved from our pathology archives in 2019. The cohort included 48 patients: 21 males and 27 females, with a mean age of 67 years (range 50-89), of which 77.1% were identified according to regional screening protocol. All hematoxylin and eosin slides were independently reviewed by each pathologist, who classified all samples according to the WHO Classification of Digestive System Tumor (Fleiss Kappa: 0.75). The immunohistochemical expression of MMR and BRAF was evaluated in 42 samples. Loss of MLH1 and PMS2 was recorded in one serrated sessile lesion (LSS) with dysplasia, but NGS analysis resulted negative. In contrast, BRAF V600E IHC resulted positive in 22 samples (52.4%), specifically in 5 hyperplastic polyps (71.4%), 10 LSS (66.6%), 5 LSS with dysplasia (45.5%) and 2 adenomatous polyps (100%), 1 TSA negative. All BRAF V600E IHC positive cases were confirmed by NGS analysis. Conclusion: To conclude, the interobserver agreement for morphological classification of serrated lesions resulted substantial; however, behind the morphological appearance, BRAF V600E resulted in predominant mutation in LSS and hyperplastic polyps, these observations confirmed the possibility to improve the classification with IHC BRAF V600E; especially for hyperplastic polyps, it may be crucial to identify precancerous lesions and different clinical management. Citation Format: Francesca Ambrosi, Costantino Ricci, Federico Chiarucci, Stefano Chilotti, Doriana Donatella Di Nanni, Angelo Gianluca Corradini, Maria Antonietta Cumiento, Dario De Biase, Michelangelo Fiorentino. What9s more in serrated lesions: interobserver agreement and molecular features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2603.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81015548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 2611: Transcription factor-nucleosome dynamics inferred from plasma cfDNA delineates tumor and tumor-microenvironment phenotype 摘要2611:从血浆cfDNA推断的转录因子-核小体动力学描述了肿瘤和肿瘤微环境表型
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2611
Satyanarayan Rao, A. Han, Alexis Zukowski, E. Kopin, P. Kabos, S. Ramachandran
{"title":"Abstract 2611: Transcription factor-nucleosome dynamics inferred from plasma cfDNA delineates tumor and tumor-microenvironment phenotype","authors":"Satyanarayan Rao, A. Han, Alexis Zukowski, E. Kopin, P. Kabos, S. Ramachandran","doi":"10.1158/1538-7445.AM2021-2611","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2611","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83030996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 2586: Association between healthy eating index score and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) 2586:前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验(PLCO)中健康饮食指数评分与胰腺癌风险的关系
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2586
Margaret Hoyt, Jianjun Zhang
{"title":"Abstract 2586: Association between healthy eating index score and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO)","authors":"Margaret Hoyt, Jianjun Zhang","doi":"10.1158/1538-7445.AM2021-2586","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2586","url":null,"abstract":"Pancreatic cancer is one of the deadliest malignancies in the US. Most cases are diagnosed in the late, non-resectable stages largely due to lack of effective screening tests. There is an urgent need to identify modifiable risk factors for primary prevention of this malignancy. To date, only a few risk factors (family history, smoking, and type-2 diabetes) have been identified for pancreatic cancer. Although several lines of evidence suggest that nutrition plays a role in pancreatic cancer, few nutrients have been consistently associated with its risk in epidemiologic studies. Therefore, the present study sought to investigate the association between the 2015 Healthy Eating Index (HEI-2015) score and pancreatic cancer risk among participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The HEI-2015 is a measure of overall diet quality used to assess how well a diet conforms to key recommendations of the 2015-2020 Dietary Guidelines for Americans. The HEI score is made up of 13 food components, with higher scores (ranged 0-100 points) indicating better dietary quality. In the present study, the HEI-2015 scores were calculated from participant responses to two food frequency questionnaires, dietary questionnaire (DQX) and dietary history questionnaire (DHQ) administered at baseline and the three-year anniversary of enrollment, respectively. During a median follow-up of 12.2 years, 279 cases of pancreatic cancer were identified among 58,477 participants who completed the DQX, while 101,721 participants who responded to the DHQ gave rise to 380 cases of pancreatic cancer over a median follow-up of 8.9 years. Hazard ratios (HR) and 95% confidence internals (CI) were estimated using Cox proportional hazards regression for total HEI score and individual score components, classified into adequacy components (total fruit, whole fruits, total vegetables, greens and beans, whole grains, dairy, total protein foods, seafood and plant proteins, and fatty acids) and moderation components (refined grains, sodium, added sugars, and saturated fats). After adjustment for confounders, no significant association between total HEI score and pancreatic cancer was identified [HR (95% CI) for quartile (Q) 4 vs. Q1: 0.86 (0.60, 1.09) for DQX and 1.03 (0.77, 1.39) for DHQ]. The individual component scores for total vegetables and added sugar in the DHQ analysis and whole grain score in the DQX analysis were inversely associated with pancreatic cancer risk [HR (95% CI) for one-point score increase: 0.89 (0.81, 0.98), 0.95 (0.91, 0.99), and 0.94 (0.89, 0.99), respectively]. In summary, our study did not find a significant association between overall diet quality and pancreatic cancer risk but revealed significant associations with total vegetables, added sugar, and whole grains in the PLCO trial. Citation Format: Margaret L. Hoyt, Jianjun Zhang. Association between healthy eating index score and risk of pancreatic cancer in the prostate, lung,","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88796070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract LB013: Clinical validation of a targeted methylation-based multi-cancer early detection test LB013:靶向甲基化多癌早期检测试验的临床验证
Prevention Research Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-LB013
E. Klein, D. Richards, A. Cohn, M. Tummala, R. Lapham, D. Cosgrove, G. Chung, J. Clement, Jingjing Gao, N. Hunkapiller, A. Jamshidi, K. Kurtzman, M. Seiden, C. Swanton, Minetta C. Liu
{"title":"Abstract LB013: Clinical validation of a targeted methylation-based multi-cancer early detection test","authors":"E. Klein, D. Richards, A. Cohn, M. Tummala, R. Lapham, D. Cosgrove, G. Chung, J. Clement, Jingjing Gao, N. Hunkapiller, A. Jamshidi, K. Kurtzman, M. Seiden, C. Swanton, Minetta C. Liu","doi":"10.1158/1538-7445.AM2021-LB013","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB013","url":null,"abstract":"Introduction: A multi-cancer early detection (MCED) test as a complement to existing screening tests could increase the number of cancer cases detected in a population, potentially improving patient outcomes and survival as well as decreasing harmful and aggressive treatments. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was designed to develop and validate a blood-based MCED test analyzing plasma cell-free DNA (cfDNA) to detect cancer signals across multiple cancer types and simultaneously predict their signal origin. Here, the results of the third and final pre-specified CCGA validation sub-study for a refined MCED test in a large cohort in preparation for clinical use are reported. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall population N=15,254). In this sub-study (n=5309), key primary objectives were to evaluate test performance for cancer signal detection (specificity, overall sensitivity, sensitivity by clinical stage) and signal origin prediction (accuracy). cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning algorithm. The classifier was trained to target a specificity of 99.4% and locked before analysis of the independent validation set. Overall, 4077 participants comprised the independent validation set with confirmed status (cancer: n=2823; non-cancer: n=1254 with non-cancer status confirmed at year-one follow-up). MCED test results are reported for this confirmed status set. Results: Mean (SD) age in the cancer and non-cancer groups was 62.6 (11.76) and 56.2 (12.63) years, respectively. Specificity for cancer signal detection was 99.5% (1248/1254; 95% confidence interval: 99.0-99.8%). Overall sensitivity for cancer signal detection was 51.5% (1453/2823; 49.6-53.3%); sensitivity increased with stage (Stage I: 16.8% [14.5-19.5%], Stage II: 40.4% [36.8-44.1%], Stage III: 77.0% [73.4-80.3%], Stage IV: 90.1% [87.5-92.2%]). Stage I-III sensitivity was 67.6% (593/877; 64.4-70.6%) in a pre-specified set of 12 high-signal cancers accounting for ~63% of annual US cancer deaths [1] and was 40.7% (863/2118; 38.7-42.9%) in all cancers. Cancer signals were detected across >50 cancer types [2]. Overall accuracy of signal origin prediction in true positives was 88.7% (87.0-90.2%). Conclusions: In this pre-specified, large-scale, clinical validation sub-study of CCGA, the MCED test detected cancer signals across >50 cancer types, which is critical to maximize the number of cancer cases detected in a population. This MCED test performed with high specificity and high accuracy of signal origin prediction. These data lay the foundation for population-scale clinical implementation of this test. 1.US Mortality Data 1969-2016 (www.seer.cancer.gov); based on 2015-2016. 2.Amin et al. CA Cancer J Clin. 2017;67:93e99. Citation Format: Eric A. Klein, Donald Richards, Allen Cohn, Mohan Tummala, Rosanna La","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89789915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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