Cancer Epidemiology and Prevention Biomarkers最新文献

{"title":"Abstract IA10: Targeted imaging of the serrated pathway for early detection of colorectal cancer","authors":"Thomas D. Wang","doi":"10.1158/1538-7755.CARISK16-IA10","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-IA10","url":null,"abstract":"Background and Significance: Colorectal cancer (CRC) is a leading cause of cancer-related mortality with ~1.4 million new cases diagnosed globally and ~690,000 annual deaths. The serrated pathway is a primary cause of CRC in the proximal colon. Sessile serrated adenomas (SSA) have flat and subtle features that are difficult to detect with conventional white light colonoscopy. Aims: We aim to identify a peptide imaging agent that binds specifically to SSA to improve visualization of pre-malignant lesions in the proximal colon. Methods: We used phage display technology with subtractive biopanning against cells with a V600E point mutation in BRAF. We performed a first-in-humans clinical study by topically administering this FITC-labeled peptide in the proximal colon of n = 38 human subjects, and performed in vivo imaging using a wide-field endoscope that is sensitive to fluorescence. Results: We identified the peptide sequence KCCFPAQ, and measured an apparent dissociation constant of kd = 72 nM and an apparent association time constant of kd = 0.174 min-1 (5.76 min). On in vivo fluorescence images, we measured a 2.43-fold greater target-to-background ratio for SSA than for normal colonic mucosa, and could distinguish SSA with 89% sensitivity and 92% specificity. We found 84% sensitivity and 91% specificity for discriminating SSA from traditional adenomas. No toxicity was attributed to the peptide in either animal or patient studies. On ex vivo images, we found the mean fluorescence intensity for SSA to be significantly greater than that for hyperplastic polyps. Conclusions: We have identified a fluorescently-labeled peptide that is safe for clinical use, and is specific for detecting SSAs in the proximal colon with wide-field imaging. This targeted imaging methodology may be useful for early detection of pre-malignant serrated lesions on routine colonoscopy. Citation Format: Thomas D. Wang. Targeted imaging of the serrated pathway for early detection of colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA10.","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78455842","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 A03: Risk prediction for gastric cancer using the GWAS-identified SNPs, Helicobacter pylori infection and lifestyle-related risk factors in a Japanese population","authors":"Hidemi Ito, I. Oze, K. Matsuo","doi":"10.1158/1538-7755.CARISK16-A03","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-A03","url":null,"abstract":"Advances in molecular genetics have the potential to impact cancer prevention. However, the contribution of this information to determining the risk of cancer of the stomach at the population level in combination with biological and lifestyle-related factors has not been evaluated. Here, we established a risk prediction model of gastric cancer using genetic, biological, and lifestyle-related risk factors as a potential practical application in interventions for cancer prevention. We conducted two independent age- and sex-matched case-control studies, the first for model derivation (697 cases and 1,372 controls) and the second (678 and 678) for external validation. Using the derivation study data, we developed a prediction model by fitting a conditional logistic regression model using the following predictors: age, ABCD classification defined by H.pylori infection and atrophic gastritis, smoking, fruit and vegetable intake, and selected GWAS-identified genotypes. Performance was assessed regarding discrimination (area under the curve, AUC), calibration (calibration plots and Hosmer-Lemeshow test) and reclassification (integrated discrimination improvement (IDI)). We preliminarily found that a combination of rs229400 , one of the GWAS-identified SNPs, H.Pylori infection, atrophic gastritis, smoking and fruit and vegetable intake provided high discriminatory accuracy and good calibration in both the derivation and validation studies, with AUCs of 0.78 (95% confidence intervals, 0.76-0.80) and 0.80 (0.77-0.82), respectively. The calibration plots of both studies stayed close to the ideal calibration line. IDI indices were 0.12 (p rs2294008 , and the other predictors. Citation Format: Hidemi Ito, Isao Oze, Keitaro Matsuo. Risk prediction for gastric cancer using the GWAS-identified SNPs, Helicobacter pylori infection and lifestyle-related risk factors in a Japanese population. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A03.","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86151327","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 A01: Gastric cancer pre-screener project: Development of a comprehensive gastric cancer risk questionnaire","authors":"H. In, Marisa Langdon-Embry, J. Wylie-Rosett, B. Rapkin","doi":"10.1158/1538-7755.CARISK16-A01","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-A01","url":null,"abstract":"Background: Gastric adenocarcinoma is the fifth most common cancer and third leading cause of cancer mortality in the world. In the US, outcomes for gastric cancer are dismal with only 28% surviving to 5 years. Upper gastrointestinal endoscopy is the gold standard for early detection of gastric tumors and used in countries with high prevalence for mass screening. However, due to the low prevalence of gastric cancer in the general U.S. population, a national screening program is not cost effective. Tools to identify patients at higher risk of gastric cancer may help identify subpopulations that should be referred for opportunistic screening. Purpose: To characterize the questionnaire development of a comprehensive gastric cancer risk assessment survey instrument that will be used to collect primary data in a large-scale case-control study. This primary data will be used to create a predictive model and determine items that best discriminate between gastric cases and controls, to ultimately create a simple pre-screening instrument that can be used in pre-diagnostic settings to identify at-risk patients who should be referred for upper GI endoscopy. Procedures: Phase 1) comprehensive literature review to identify established risk factors for gastric cancer. Survey instruments that established individual risks for gastric cancer were brought together to create the initial questionnaire. Phase 2) questionnaire refinement through focus groups and cognitive interviews. Focus groups were used to examine the measure for wording, layout, clarity and relevance. The item pool was then translated into Mandarin Chinese, Spanish and Korean, and cognitive interviews were conducted to ensure the questionnaire carried semantic equivalence across languages. Interview notes were aggregated on a question-by-question basis to produce a cognitive interviewing outcome report to guide questionnaire revisions. Results: A 300-item questionnaire was adapted from 16 survey instruments previously validated for gastric cancer. Identified risk factors for gastric cancer included dietary habits, demographics, racial disparities, Helicobacter pylori exposure, smoking and alcohol habits, socioeconomic status and pre-existing conditions. Only risk factors that were not hereditary and could be determined in questionnaire format were included. 29 English-speaking participants with and without gastric completed survey questions and provided feedback in focus group discussions. Participants noted items that needed clarification or simplification, or were redundant or irrelevant. Special attention was given to complex measures such as dietary history and acculturation to ensure that questions about details of ethnicity and timing of immigration were sensitive, appropriate and non-threatening. 60 gastric cancer cases and controls participated in cognitive interviews to ensure the questionnaire carried semantic equivalence across languages. Participants included 40 first-generation immigr","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80878017","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 IA13: A practical approach to reducing the burden of ovarian cancers","authors":"A. Douglas","doi":"10.1158/1538-7755.CARISK16-IA13","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-IA13","url":null,"abstract":"Ovarian cancer has seen a modest improvement in five-year survival over the past three decades. It is well known that the lack of further success is solely due to the advanced stage at diagnosis for most women with ovarian cancers. To reduce the burden of ovarian cancer, we must decrease the incidence (primary prevention), improve early detection (secondary prevention), or develop more effective treatments for newly diagnosed disease (tertiary prevention). Large scale screening trials using traditional methods of imaging and tumor markers have not led to meaningfully stage migration, reduction in mortality, or widespread clinical adoption. In fact, the FDA recently issued a safety alert about the risks associated with the use of tests being marketed as ovarian cancer screening tests. The FDA was specifically concerned about ovarian cancer screening tests being used in lieu of established risk-reduction approaches. This presentation will review practical approaches to reducing the burden of ovarian cancer through primary, secondary, and tertiary prevention. Genetic testing of probands for BRCA1 and BRCA2 germline mutations alone and cascade testing of relatives are currently available approaches to reduce the incidence of ovarian cancer by more than 10%. This tactic is consistent with professional guidelines and has the added advantage of identifying therapeutic options for ovarian cancer patients that could contribute to tertiary prevention efforts today and in the future. Lower penetrant genes also have the potential to lead to primary prevention through risk reduction strategies, but further data is required to firmly establish appropriate age-based recommendations. The identification of the distal fallopian tube as a likely site of origin for most ovarian cancers has opened a new domain for ovarian cancer primary prevention. Some governmental organizations suggest population-based bilateral salpingectomy at the time of any pelvic or abdominal surgery for primary prevention of ovarian cancers considering that one-third of US women will have a hysterectomy by age 70. The reasons for success and failure of this approach will be discussed. The fallopian tube as the site of origin for ovarian cancers has led to new approaches for early detection. The anatomy of the fallopian tube and its proximity to the lower genital tract has led to the development of creative strategies for sampling derivatives of precursor lesions and early invasive disease. Collection of uterine fluid for proteomic analyses and DNA sequencing holds promise for enrichment of cancer-specific biomolecules. Cervical pap smears and the collection of vaginal secretions offer a less invasive approach to early detection through similar theoretical avenues. Through the study of long-term survivors of advanced stage high-grade serous ovarian cancer, we have learned that primary surgical cytoreduction reduces the risk of cancer recurrence and serves as a useful approach to tertiary preve","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84297702","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 PR16: Effect of cancer risk and patient preferences on net benefit of lung cancer screening: A personalized lung cancer screening model","authors":"Pianpian Cao, T. Caverly, R. Hayward, R. Meza","doi":"10.1158/1538-7755.CARISK16-PR16","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-PR16","url":null,"abstract":"Background: Most low-dose computed tomography (LDCT) lung cancer screening guidelines recommend shared-decision making (SDM) before initiating screening. Indeed, Medicare requires evidence of SDM for reimbursement. The clinical benefit of screening, however, varies dramatically across eligible patients. Also, the harms of LDCT, such as fear and unnecessary procedures incurred by false positive results, can be quite substantive. Clinicians and health systems, therefore, need individually tailored screening guidance, depending on the extent of benefit. To this end, we developed the Personalized Lung Cancer Screening Model, a microsimulation model that estimates individual-specific health gain from LDCT screening. This model evaluates the potential effects of patient preferences on health gains across low- and high-benefit groups. Methods: We estimated the effects of LDCT screening on lung cancer outcomes and quality-adjusted life years (QALYs). Our natural history model was built based on previously validated lung cancer models, constructed by utilizing different data sources: two large randomized lung cancer screening trials (NLST and PLCO) and the Surveillance, Epidemiology and End-Results cancer registry. For this study, we simulated a nationally representative sample of 1 million patients eligible for LDCT screening, whose risk profiles mimic adult smokers participated in the National Health Interview Study (NHIS) from 2010 to 2014. We quantified patient preferences using literature-derived utilities (e.g., the burden of testing, false-positive diagnoses, treatment, and complications that result from the screening and treatment process). Besides inherent uncertainty in some utility measures, our primary aim was to understand the effect of varying patient preferences on the net benefit of screening. Therefore, we performed a further analysis by varying utilities over a plausible range. Results: Our model predictions of lung cancer incidence and mortality rates in the NLST and PLCO participants matched well to the observed rates. Similarly, average incremental QALY gains were consistent with that found in a previous NLST-based cost-effectiveness analysis. Among the simulated NHIS population, incremental QALY gains varied significantly across differing baseline risk of developing lung cancer (range in base-case analysis: 2 QALYs lost per 100 people screened to 6 QALYs gained per 100 screened). Our analysis for patient preferences showed that the magnitude of net benefit from LDCT screening is not very sensitive to patient9s views of the burdens and harms of testing and treatment if the patient9s baseline lung cancer risk was above the third decile. That is, even assuming unfavorable preferences, those above 3rd decile of risk generally experienced net benefit, while the less than 3rd decile of baseline risk was a more preferences sensitive zone. Conclusion: Results from our Personalized Lung Cancer Screening Model demonstrate the importance of an ","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90447364","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 B18: Improving pancreatic cancer risk prediction through early detection","authors":"C. Snyder, S. Haag, Nickie L. Adams, J. Hess, Breann Paskett, E. Borazanci","doi":"10.1158/1538-7755.CARISK16-B18","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-B18","url":null,"abstract":"Introduction: It is estimated that by 2030 pancreatic cancer will be the second leading cause of cancer deaths in the US. Currently, only 9% of newly diagnosed pancreatic cancer is localized and 5-year survival is 7%. Due to most pancreatic cancers (PC) presenting at a later stage with poor overall survival, early detection methods must be implemented to improve treatment outcomes. Yet, effective early screening guidelines do not exist for pancreatic cancer. Our Early Detection Program (EDP) provides personalized early detection including risk assessment, screening, and genetic testing. We aim to evaluate risk assessment criteria, establish a database to delineate a pattern of characteristics, and utilize a biospecimen repository and molecular based technologies to map novel biomarkers for early detection. Methods: This is a prospective study for individuals with a family history or a germline mutation consistent with risk for developing PC. Patients are eligible based on risk assessment criteria and stratified into 3 groups as defined by best available evidence based upon the CAPS Consortium and a prior prospective screening study. Patients are assessed at initial visit, have yearly screenings, and each case is discussed at a multi-disciplinary pancreatic tumor board. At the initial visit, patients undergo a thorough history and physical exam, genetic testing for germline mutations, routine blood tests along with Ca19-9 tumor marker and if indicated, MRI/MRCP abdomen, GI consult and EUS. Patients defined as average risk have one family member diagnosed with PC above the age of 55 years. Those at moderate risk are individuals with two or more first, second, third degree relatives with PC or one first degree relative with PC diagnosed Results: Since the inception of the EDP (IRB approved November 2015), there have been no PC cases identified. Current participants include individuals age 34 to 79 with a mean age of 59. According to the current risk criteria 22% have a low PC risk, 26% have a moderate risk, and 52% have a high PC risk. All were advised a genetic assessment. Of the current sample, 36% were male and 64% were female, 55% used tobacco in the past, and 9% currently use tobacco. The BMI average is 26.85 (overweight), 2 participants have Type 2 diabetes, and several have had other types of cancer such as: 5% breast, 2% colon, 2% ovarian, 1% thyroid, and 38% had basal cell skin cancer. 26% had germline mutations and 10% with intraductal papillary mucinous neoplasm (IPMN). Initial results reveal there is a level of anxiety associated with PC risk and some indicate their chance to develop cancer is high (M = 5.05, SD = 1.80). Compared to other people, participants stated their chance of getting cancer sometime in their life is a little higher (M = 4.10, SD = .85), and their ability to exercise control over their cancer risk was moderate (M = 2.6, SD .93). Conclusions: Although the EDP is still recruiting patients, the effectiveness of our scr","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73150840","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 PR17: Comprehensive colorectal cancer risk prediction to inform personalized screening and intervention","authors":"Jihyoun Jeon, S. Berndt, H. Brenner, P. Campbell, A. Chan, J. Chang-Claude, Mengmeng Du, G. Giles, Jian Gong, S. Gruber, T. Harrison, M. Hoffmeister, L. LeMarchand, Li Li, J. Potter, G. Rennert, R. Schoen, M. Slattery, E. White, M. Woods, U. Peters, L. Hsu","doi":"10.1158/1538-7755.CARISK16-PR17","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-PR17","url":null,"abstract":"Background and Aims: Colorectal cancer (CRC) is one of the most preventable and treatable cancers when detected early via screening. The current screening guidelines for CRC recommend exams only based on age, family history, and previous screening results. Multiple environmental and lifestyle risk factors, however, have been established or suspected for CRC, as have many common genetic susceptibility loci. It is critical to utilize this information to better stratify individuals into low- and high-risk groups for optimized and personalized screening and intervention recommendations. Methods: Using data from two large consortia (8421 CRC cases and 9767 controls): the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colorectal Transdisciplinary study (CORECT), we developed risk prediction models for men and women based on family history, environmental and lifestyle risk factors, and known CRC susceptibility loci identified through genome-wide association studies. We constructed an environmental risk score (E-score) as a weighted sum of 19 established or potential environmental and lifestyle risk factors for CRC with weights obtained from a multivariate logistic regression analysis. Similarly, we also constructed a genetic risk score (G-score) using 64 common variants associated with CRC risk. We evaluated the discriminatory accuracy of risk prediction models by calculating the area under the Receiver Operating Characteristic curve (AUC), correcting for potential overestimating by using the training data set. Our models also estimate absolute risk of developing CRC given various risk profiles, and provide recommended ages for the first endoscopic screening exam. Results: Both the E-score and the G-score are independent predictors of CRC risk, and models that incorporate both scores improve the discriminatory accuracy significantly compared to family history-only models. Compared to the model that includes only family history, the E-score significantly improves the discriminatory accuracy for both men (AUC = 0.62 vs. 0.53, p-value Conclusions: Our risk prediction models incorporating both comprehensive environmental and lifestyle risk factors, and known CRC common genetic variants provide more accurate estimation of CRC risk. These models will be useful for recommending individually tailored screening and intervention strategies to prevent this common cancer. This abstract is also being presented as Poster B17. Citation Format: Jihyoun Jeon, Sonja I. Berndt, Hermann Brenner, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Mengmeng Du, Graham Giles, Jian Gong, Stephen B. Gruber, Tabitha A. Harrison, Michael Hoffmeister, Loic LeMarchand, Li Li, John D. Potter, Gad Rennert, Robert E. Schoen, Martha L. Slattery, Emily White, Michael O. Woods, Ulrike Peters, Li Hsu. Comprehensive colorectal cancer risk prediction to inform personalized screening and intervention. [abstract]. In: Proceedings of the AACR Special Conference: I","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80916022","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 B13: Adherence to cancer-specific prevention recommendations reduces risk of cancer in participants in Alberta's Tomorrow Project, Alberta, Canada","authors":"Jian-Yi Xu, J. Vena, H. Whelan, P. Robson","doi":"10.1158/1538-7755.CARISK16-B13","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-B13","url":null,"abstract":"Background: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published specific recommendations on food and nutrition, physical activity, body composition, and other modifiable risk factors in 2007 with the aim of reducing risk for cancer. However, inconsistent results have been reported regarding the impact of following these recommendations on cancer incidence and cancer mortality. Further, the impact of adhering to cancer-specific recommendations issued by WCRF/AICR has not been evaluated in a Canadian population. Objective: The objective of this study was to estimate the association between adherence to cancer-specific prevention recommendations and subsequent cancer risk in a prospective Canadian cohort; Alberta9s Tomorrow Project (ATP). Design: ATP is a large population-based cohort of 55,000 adults who will be followed for up to 50 years to study the etiology of cancer and chronic disease, providing information that will help establish targeted prevention strategies. In the present study, 25,100 adult Albertans (35-69 years) with no previous diagnosis of cancer were recruited into ATP from 2001 to 2009 by random digit dialing. Self-administered questionnaires (Health and Lifestyle Questionnaire, Canadian Diet History Questionnaire (past year food frequency questionnaire), and Past Year Total Physical Activity Questionnaire) were used to collect participants9 health and lifestyle information. A composite score was constructed to reflect each participant9s overall adherence to seven WCRF/AICR personal recommendations, including body fatness, physical activity, consumption of fruits and vegetables, consumption of red meat, alcoholic drinks, dietary supplements intake, and tobacco exposure (including second hand smoke). Incidence cancer cases (excluding non-melanoma skin cancer) were identified through linkage with the Alberta Cancer Registry in 2015. Multivariable Cox proportional hazard regression models were employed to assess the association (HRs and 95% CIs) between the adherence composite score and risk of developing cancer. Results: Over a median of 10.0 years (252,120 person-years) follow-up, 1,709 participants developed cancer. After adjustment for potential confounding covariates, participants who were most adherent to WCRF/AICR recommendations (composite score: 4-7) were 19% (HR 0.81, 95% CI: 0.71-0.91) less likely to develop cancer when compared to those who were least adherent to the same recommendations (composite score: 0-2). Each unit increase in the composite score corresponded to an 8% (HR 0.92, 95% CI: 0.88-0.96) reduction in risk of developing cancer. When stratified by sex, the associations remained significant for women, but not for men. Conclusions: Adherence to cancer-specific prevention recommendations may reduce the risk of developing cancer. The adherence composite score constructed in this study may serve as a surrogate lifestyle indictor for predicting those at high risk o","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80926368","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 PR06: Using frailty models to improve familial cancer risk prediction","authors":"Theodore Huang, D. Braun, M. Gorfine, G. Parmigiani","doi":"10.1158/1538-7755.CARISK16-PR06","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-PR06","url":null,"abstract":"There are numerous statistical models used to identify individuals at high risk of cancer due to inherited mutations. We focus on models using Mendelian laws of inheritance to calculate the probability that a counselee is a mutation carrier and their future risk of cancer based on family history and known mutation prevalence and penetrance (the probability of having a disease at a certain age given the person9s genotype). Mendelian risk prediction models for various cancers have previously been developed. These models include BRCAPRO, which identifies individuals at high risk for breast or ovarian cancer by calculating the probabilities of germline deleterious mutations in BRCA1 and BRCA2. These models do not account for the heterogeneity of risk across families due to sources such as environmental or unobserved genetic risk factors. We aim to improve breast cancer risk prediction in the BRCAPRO model by incorporating a frailty model that contains a family-specific variate to account for this heterogeneity. We apply our proposed model to data from the Cancer Genetics Network, and preliminary results show that model calibration (measured by the ratio of observed to expected number of events) improves, while discrimination (measured by the area under the receiver operating characteristic (ROC) curve) remains the same. This abstract is also being presented as Poster A18. Citation Format: Theodore Huang, Danielle Braun, Malka Gorfine, Giovanni Parmigiani. Using frailty models to improve familial cancer risk prediction. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr PR06.","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87038849","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 PR03: Association of environmental risk factors, family history, and polygenic risk scores with chronic lymphocytic leukemia","authors":"G. Kleinstern, Dennis P. Robinson, T. Call, M. Liebow, S. Sanjosé, Y. Benavente, J. Cerhan, S. Slager","doi":"10.1158/1538-7755.CARISK16-PR03","DOIUrl":"https://doi.org/10.1158/1538-7755.CARISK16-PR03","url":null,"abstract":"Background: Chronic lymphocytic leukemia (CLL) is a lymphoid malignancy with a strong genetic component. There are over 30 common single nucleotide polymorphisms (SNPs) associated with the risk of CLL. Moreover, in the InterLymph Subtypes Project a number of non-genetic exposures have been found to be associated with CLL, including family history (FH), height, history of atopic conditions, UV radiation, and farming exposures. However there has not been a study evaluating the joint effects among these genetic and non-genetic factors with CLL risk. Methods: Using the Mayo Clinic CLL case-control study of 587 newly diagnosed CLL cases and 790 controls, we performed analyses evaluating joint effects of genetic and non-genetic factors. For genetic effects, we computed a polygenetic risk score (PRS), a weighted averaged of the number of risk alleles across 34 SNPs, with the weights being the log of the odds ratio for each SNP. Exposure data was available for 65% of the cases and 79% of the controls. We evaluated individual and joint associations of FH of any hematological malignancy, total sun exposure categorized by quartiles based on the controls, ever living or working on a farm, any atopy, any allergies, asthma, height, and PRSs categorized by quintiles based on the controls. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: In our preliminary results, the frequency of CLL cases in the upper PRS quintile was 49% while in the lowest quintile only 5%. The PRS has a strong evidence of association with CLL (OR= 3.04, CI =2.20-4.20 for highest versus the middle quintile). When adjusting for PRS, we still found a positive association with FH for any hematological malignancy (OR = 1.90, CI = 1.25-2.88), FH of non-Hodgkin lymphoma (OR = 2.02, CI = 1.08-3.79), and FH of leukemia (OR = 1.73, CI = 0.98-3.07). When stratifying by FH, the upper quintile of the PRS had a 5.85-fold (CI = 1.69-20.3) increased risk of CLL relative to those in the middle quintile in the FH strata, and a 2.65-fold (CI = 1.75-4.01) increased risk in the non-FH strata. After adjusting for PRS, FH and age, there remained an inverse association with sun exposure in the highest quartile (hours per week) (OR = 0.49, CI = 0.31-0.79) and a positive association with height (per 10 cm change) (OR = 1.37, CI = 1.17-1.62), but there were no associations with atopy, any allergies, history of asthma, or farming. No statistical evidence of an interaction among the variables was observed. Conclusions: We found evidence of independent effects among the genetic and non-genetic factors with risk of CLL. Among these factors, the PRS had the largest effect size. Although we did not observe any statistical interactions, larger sample sizes are warranted to fully evaluate these effects on risk of CLL. We are currently increasing our sample size through collaboration with other research groups. Final results will be presented in th","PeriodicalId":9487,"journal":{"name":"Cancer Epidemiology and Prevention Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74390453","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}