Prevention Research最新文献

{"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}

{"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}

{"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}

{"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}

{"title":"Abstract 2590: Genomic analysis points to fibrosis and changes in fat metabolism in oral cancer progression","authors":"G. Unger, B. Wuertz, C. L. Pruett, M. Watkins, P. Gaffney, F. Ondrey","doi":"10.1158/1538-7445.AM2021-2590","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2590","url":null,"abstract":"Head and neck cancer long term survival has only experienced marginal gains over the past 3 decades. Further, there is inadequate understanding of the biology of carcinogenesis and recurrence, as well as its relation to the microenvironment. Deeper understanding of these areas would provide improved molecular target identification. In pursuit of this goal, a small clinical trial collected lesion and adjacent normal-appearing mucosa for subsequent RNA-seq analysis. Patients were grouped by post-surgical pathology as either precancer (hyperplasia - severe dysplasia) or cancer (carcinoma in situ - early stage invasive cancer). Following identification of differentially expressed (DE) genes, DE genesets were submitted for Ingenuity Pathway Analysis (IPA). Hierarchical clustering illustrates distinct separation between lesion and perilesional normal mucosa of the top 100 DE genes. Among the top 25 dysregulated pathways, 50% were associated with creation of fibrotic tumor microenvironment (TME), 20% were related to changes in immune populations inhabiting the TME and 10% devoted to metabolism changes. Subgroup analysis, (precancer vs. cancer), revealed dysregulation of metabolism (~50%) predominating in precancer. Metabolism remained an important dysregulation at 30% of the top 25 pathways in cancer. Protein network analysis, (Metascape on-line tool), confirmed IPA results, illustrating an extensive, previously undescribed, interconnectedness of fibrosis with shifts in fatty acid metabolism from oxidative to gluconeogenesis, providing a foundation for choosing targets amenable to cancer prevention. Several notable pathways are likely contributed to by inflammatory and other cells in the milieu, not precancer cells themselves. So, we dove deeper, using EpIC (Epitope Immunogenicity Characterization) algorithm to assess relative percentages of non-tumor cells based on 20-count gene signatures. Gene expression favored a profile of significantly increasing cancer-associated fibroblasts, decreasing CD-8 killer T cells, and increasing vascular endothelial cells during progression, with macrophage content slightly increasing in cancer specimens. These findings suggest interaction between immunoinflammatory milieu and precancerous cells promoting malignancy. Several high yield target pathways are related to published mechanisms of action for drugs of high interest to our cancer prevention program (pioglitazone/metformin). Further, we confirmed protein network analysis in an additional oral carcinoma dataset from Conway et. al, (Oncotarget 2015). Citation Format: Gretchen M. Unger, Beverly R. Wuertz, Charles L. Pruett, Matthew Watkins, Patrick M. Gaffney, Frank G. Ondrey. Genomic analysis points to fibrosis and changes in fat metabolism in oral cancer progression [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 2590.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84742349","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}

{"title":"Abstract 2593: Racially diverse primary esophageal cell cultures for evaluating mitigation of bile-induced injury","authors":"Katherine M. Weh, D. Turgeon, A. Howell, L. Kresty","doi":"10.1158/1538-7445.AM2021-2593","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2593","url":null,"abstract":"Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for EAC development. GERD and esophagitis occur at similar rates among Blacks and Caucasians; yet, progression to EAC is significantly elevated among Caucasians. Unique protective factors in the epithelium of Blacks may contribute to this disparity. Our research team recently reported that the detoxification enzyme GSTT2 is higher in the esophageal squamous epithelium of Blacks compared to Caucasians with potential linkages to previously identified genomic variants in the GSTT2 locus (a 37 kb deletion and a 17 bp promoter duplication among Caucasians). Thus, the current study seeks to evaluate whether primary esophageal cell cultures isolated from Black or Caucasian cohorts can serve as discerning and relevant model systems to investigate risk factors linked to EAC progression, assess efficacy of mitigating agents and differential responses linked to race. We have shown that cranberry proanthocyanidins (C-PAC) mitigate DNA damage associated with reflux through upregulation of GSTT2 in a rat surgical model of reflux-induced EAC, but whether effects are recapitulated in humans or differentially based on race remains unknown. Herein we isolated normal primary esophageal epithelial cells from Black and Caucasian patients and assessed GSTT2 genotype, GSTT2 protein levels and cellular viability following exposure of the cultures to a bile acid cocktail (BAC) [0.2mM] with and without C-PAC [50µg/ml] treatment. Constitutive levels of GSTT2 were 1.7-fold higher in Blacks than Caucasians, with 71% of Blacks identified as high expressors compared to 33% of Caucasians. Pretreatment (48h) of primary cultures with C-PAC induced GSTT2 levels in all but one Black-derived culture which already expressed high basal levels. GSTT2 induction in normal epithelial cultures by C-PAC was greatest in cells with constitutively low GSTT2 expression; however, upon BAC challenge C-PAC effectively mitigated BAC-induced reductions in GSTT2 levels and subsequent loss of normal cell viability regardless of basal GSTT2 expression or race. C-PAC treatment pre- plus post-BAC imparted no additional benefit over pretreatment alone in preserving viability but did further increase GSTT2 levels. Next steps include expanding our panel of primary cultures and conducting nano LC-MS/MS proteomic profiling of Black and Caucasian-derived cultures treated with vehicle, BAC, C-PAC and BAC + C-PAC, with stratification based on GSTT2 basal expression. Taken together these data support that C-PAC may be used as an efficacious non-toxic agent serving to promote epithelial fitness and resiliency against the biologic and molecular sequelae linked bile acid-induced esophageal injury and progression to EAC. Citation Format: Katherine M. Weh, Danielle K. Turgeon, Amy Howell, Laura A. Kresty. Racially diverse primary esophageal cell cultures for evaluating mitig","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84878482","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}

{"title":"Abstract 2530: Differences in mRNA expression of a candidate gene, between normal cervical tissue and cervical premalignant lesions","authors":"Ines Benedetti, Reinhard Rodríguez, Lía Barrios","doi":"10.1158/1538-7445.AM2021-2530","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2530","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87582533","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}

{"title":"Abstract LB227: Automated image registration and alignment facilitates assessment of change in pigmented lesions of patients at risk for melanoma","authors":"W. Maguire, Paul H. Haley, C. M. Dietz, M. Hoffelder, C. S. Brandt, Robin Joyce, Melissa D. Wilson, Darcy Ploucha, Christopher P Minnier, C. Sander, Hong Wang, H. Zarour, K. Mitchell, Ellen K. Hughes, J. Kirkwood","doi":"10.1158/1538-7445.AM2021-LB227","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB227","url":null,"abstract":"Introduction: Melanoma develops either de novo or from non-obligate precursor lesions known as atypical/dysplastic nevi. Assessment of change in number and morphology of pigmented cutaneous lesions over time is critical to early detection of skin cancers and may provide preliminary signals of efficacy in early phase therapeutic prevention trials for melanoma. Despite the use of total body digital photography for at least 20 years to document the presence of these lesions, as well as recent progress in computer-aided diagnosis of lesions in clinical images, automated methods to characterize the evolution of skin lesions are still lacking. The purpose of this study was to develop and validate a computer vision approach to facilitate detection and quantification of changes in nevi in serial digital photographs. Methods: The ‘DermaViz9 mathematical algorithms were developed to register nevi between sequential images and to align images for improved comparison. The technique is based on the bispectrum algorithm, modified to adapt for human skin changes. Adaptive normalization techniques adjust for lighting and skin tone variations. Warping and shear of skin are accommodated by a hierarchical iteration of these algorithms coupled with probabilistic matching techniques for accurate alignment. The technology allows both for improved qualitative comparison by clinicians when the aligned images are toggled between dates, and for digital quantification of changes in (a)symmetry, (b)order, (c)olor, and (d)iameter of the lesions. In this pilot study, serial posterior truncal photographs from 17 patients with multiple atypical nevi and a history of melanoma were obtained from a pre-existing image and nevus biobanking protocol database at our institution. De-identified images were processed and analyzed with DermaViz software, and results were validated by a panel of Melanoma Program clinicians. Results: DermaViz software had a high sensitivity for detection of cutaneous lesions as small as 2mm, which was limited by the quality of the archival photographs. The software registered specific nevi accurately in most cases, with sight errors in a small number of lesions that were primarily located at the edges of the images. In the 17-patient pilot study, registration and alignment of serial images enabled clinicians to identify new and enlarged nevi in 3 to 11 additional patients vs the unregistered images. Quantification with DermaViz correlated with physician assessment of new and enlarged nevi in 90% of evaluated lesions. Conclusion: Software has been designed, applied, and validated that dramatically improves detection of changes in nevi over time and enables quantification of these changes. It helped clinicians to identify numerous changes that were missed in the original unregistered images. We plan to incorporate an expanded ruler and color balance tape in future photographs for improved analyses of border, color, and size changes. Dermaviz will be used in a","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88305835","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}

{"title":"Abstract 2585: Dietary isoflavone intake and lung cancer risk: an analysis using data from the prostate, lung, colorectal, and ovary (PLCO) trial","authors":"Qian Wang, Meng Ru, P. Boffetta","doi":"10.1158/1538-7445.AM2021-2585","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2585","url":null,"abstract":"Introduction: Dietary isoflavones are mainly from soy-based foods and are widely consumed in Asian countries. Isoflavone has a similar chemical structure to estrogen and has been suggested to decrease the risk of breast cancer by acting as an estrogen antagonist. Lung cancer development was also suggested to be affected by estrogen signaling. We aim to explore isoflavone intake and lung cancer risk using the prospective PLCO trial. Methods: Data regarding dietary intake using the food frequency questionnaire, demographic and reproductive information and lung cancer diagnosis were extracted. The associations between lung cancer risk and isoflavone intake (in quartiles) overall and stratified by gender and smoking status were calculated using the Cox proportional hazard models adjusting for potential confounders. SAS 9.4 were used to perform all statistical analyses. Results: During the 1,215,948 person-year follow-up, a total of 1,706 lung cancer cases were diagnosed. Overall (Table), the highest quartile of isoflavone intake was associated with 26% reduced risk of lung cancer compared to the lowest quartile. When the analysis was stratified by gender and further by smoking status (never vs ever), the decreased risk was only observed among male ever smokers (Q4 vs Q1: HR=0.78, 95%CI: 0.64-0.96) but not their female counterparts (Q4 vs Q1: HR=0.85, 95%CI: 0.68-1.08). Discussion: This is the first prospective cohort study investigating isoflavone intake and lung cancer risk and we found a protective effect of isoflavone intake against lung cancer risk particularly among male ever smokers, despite an overall lower isoflavone intake among the US populations compared to the Asian populations. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of isoflavones on lung carcinogenesis and the interactions between isoflavones, smoking and endogenous estrogens. Citation Format: Qian Wang, Meng Ru, Paolo Boffetta. Dietary isoflavone intake and lung cancer risk: an analysis using data from the prostate, lung, colorectal, and ovary (PLCO) trial [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 2585.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"163 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86223332","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}

{"title":"Abstract 2600: Deep-LIBRA: An artificial intelligence approach for fully-automated assessment of breast density in digital mammography","authors":"O. H. Maghsoudi, Scott Christopher, A. Gastounioti, Lauren Pantalone, Fang-Fang Wu, Eric A. Cohen, Winham Stacey, E. Conant, C. Vachon, D. Kontos","doi":"10.1158/1538-7445.AM2021-2600","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2600","url":null,"abstract":"Accurate estimation of mammographic breast density could aid in augmenting breast cancer risk assessment for women undergoing breast screening with full-field digital mammography (FFDM). Breast density can be estimated from FFDM and is most commonly assessed in the clinic by visual grading into one of the four categories defined by the American College of Radiology BI-RADS. However, BI-RADS density assessment is highly subjective and does not provide a quantitative, continuous measure of percent density (PD), which would allow for more refined risk stratification and assessment of density changes. Here, we introduce Deep-LIBRA, an artificial intelligence (AI) tool for fully-automated assessment of breast PD from FFDM images. Two key modules form the core of Deep-LIBRA: 1) an implementation of a modified U-Net architecture for breast segmentation and 2) a radiomic machine learning module that performs PD estimation within the segmented breast region. To develop and validate Deep-LIBRA, raw (i.e., \"For Processing\") FFDM images (Selenia Dimensions, Hologic Inc.) acquired at two breast cancer screening practices were retrospectively analyzed. For the breast segmentation module, we used a total of 12,100 FFDM studies from 2,200 individual women and a 90%-10% split-sample training-validation approach, using the Dice coefficient to evaluate the accuracy of Deep-LIBRA versus ground-truth manual breast segmentation. For the PD estimation module we used a total of 3,304 FFDM images from 1,652 individual women; manual PD scores obtained with the widely used Cumulus software were used as the \"gold standard\" in a three-fold cross-validation setting to assess the accuracy of Deep-LIBRA in PD estimation. PD estimates from Deep-LIBRA were also compared with breast density estimates from the commercially available Volpara software. Breast segmentation had a Dice coefficient of 95.31% when compared to ground-truth manual breast segmentation in the validation set. Deep-LIBRA average differences from ground-truth PD scores in the three cross-validation folds were 4.91%, 4.65%, and 4.22%, while Volpara had corresponding average differences of 6.20%, 6.01%, and 5.94%. Deep-LIBRA PD scores were also significantly different from Volpara PD (t-test p-value Citation Format: Omid Haji Maghsoudi, Scott Christopher, Aimilia Gastounioti, Lauren Pantalone, Fang-Fang Wu, Eric A. Cohen, Winham Stacey, Emily F. Conant, Celine Vachon, Despina Kontos. Deep-LIBRA: An artificial intelligence approach for fully-automated assessment of breast density in digital mammography [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 2600.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82157735","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}