Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology最新文献

{"title":"5-Alpha Reductase Inhibitor Use and Prostate Cancer Prevention: A Victim of the Times?","authors":"Robert J Hamilton","doi":"10.1158/1055-9965.EPI-22-0338","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-22-0338","url":null,"abstract":"<p><p>Vaselkiv and colleagues present strong evidence of the long-term safety of 5-alpha reductase inhibitor (5-ARI) use. They demonstrated no association with developing advanced prostate cancer, nor dying of prostate cancer. This commentary covers the strengths and weaknesses of the article, and highlights the long and vacillating journey 5-ARIs and prostate cancer prevention have traveled. As 5-ARIs preferentially prevent low-grade prostate cancer, a fact confirmed in the study by Vaselkiv and colleagues, this commentary highlights how 5-ARI chemoprevention may be irrelevant now. With increasing use of active surveillance for low-grade prostate cancers found, and prebiopsy MRI and biomarkers shifting focus to only find those clinically significant cancers, it maybe that 5-ARIs are a victim of the times in their chemoprevention role. See related article by Vaselkiv et al., p. 1460.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1259-1260"},"PeriodicalIF":3.8,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40551764","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":"Cancer in the Elderly-Reply.","authors":"Cecilia Radkiewicz,&nbsp;Jessica Järkvik Krönmark,&nbsp;Hans-Olov Adami,&nbsp;Gustaf Edgren","doi":"10.1158/1055-9965.EPI-22-0324","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-22-0324","url":null,"abstract":"","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1506"},"PeriodicalIF":3.8,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40551760","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":"Multicancer Early Detection Technologies: A Review Informed by Past Cancer Screening Studies.","authors":"Sana Raoof,&nbsp;Richard J Lee,&nbsp;Kunal Jajoo,&nbsp;Joseph D Mancias,&nbsp;Timothy R Rebbeck,&nbsp;Steven J Skates","doi":"10.1158/1055-9965.EPI-21-1443","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-21-1443","url":null,"abstract":"<p><p>More than 75% of cancer-related deaths occur from cancers for which we do not screen. New screening liquid biopsies may help fill these clinical gaps, although evidence of benefit still needs to be assessed. Which lessons can we learn from previous efforts to guide those of the future? Screening trials for ovarian, prostate, pancreatic, and esophageal cancers are revisited to assess the evidence, which has been limited by small effect sizes, short duration of early-stage disease relative to screening frequency, study design, and confounding factors. Randomized controlled trials (RCT) to show mortality reduction have required millions of screening-years, two-decade durations, and been susceptible to external confounding. Future RCTs with late-stage incidence as a surrogate endpoint could substantially reduce these challenges, and clinical studies demonstrating safety and effectiveness of screening in high-risk populations may enable extrapolation to broader average-risk populations. Multicancer early detection tests provide an opportunity to advance these practical study designs. Conditional approvals based on RCTs with surrogate endpoints, contingent upon real world evidence generation and continuation of trials to definitive endpoints, may lower practical barriers to innovation in cancer screening and enable greater progress.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1139-1145"},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40316837","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":"A Contemporary Analysis of Racial and Ethnic Disparities in Diagnosis of Early-Stage Breast Cancer and Stage-Specific Survival by Molecular Subtype.","authors":"Kristin M Primm,&nbsp;Hui Zhao,&nbsp;Daphne C Hernandez,&nbsp;Shine Chang","doi":"10.1158/1055-9965.EPI-22-0020","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-22-0020","url":null,"abstract":"<p><strong>Background: </strong>Prior studies of breast cancer disparities have focused primarily on differences between Black and White women, yet contemporary patterns of disparity for other groups are not well understood. We examine breast cancer disparities by stage at diagnosis across nine racial and ethnic groups.</p><p><strong>Methods: </strong>The SEER 18 registries identified 841,975 women diagnosed with breast cancer from 2000 to 2017. Joinpoint models assessed trends in diagnosis stage and survival. Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox models compared survival of groups by stage and molecular subtype.</p><p><strong>Results: </strong>Black, American Indian, Southeast Asian, South Asian, Pacific Islander, and Hispanic women were less likely than white women to be diagnosed with early stage breast cancer. Among those diagnosed at early stage, Hispanic, American Indian, Pacific Islander and Black women were 9%, 14%, 22%, and 39% (respectively) more likely than White women to die from breast cancer, whereas Asian subgroups had lower risk of death. Among those diagnosed at late stage, Black women were 18% more likely than White counterparts to die from breast cancer, and survival disparities for Black women persisted across all subtypes and stages, (except late stage HR-/HER2-). East Asian women with early stage HR+/HER2- tumors had better survival than White women.</p><p><strong>Conclusions: </strong>Persistent disparities in early detection and survival of breast cancer demand further work to address and reduce disparities across the cancer continuum.</p><p><strong>Impact: </strong>Results have implications for efforts to reduce entrenched racial and ethnic disparities in breast cancer early detection and survival.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1185-1194"},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40312962","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":"Establishing 24-Hour Urinary Sucrose Plus Fructose as a Predictive Biomarker for Total Sugars Intake.","authors":"Laurence S Freedman,&nbsp;Victor Kipnis,&nbsp;Douglas Midthune,&nbsp;John Commins,&nbsp;Brian Barrett,&nbsp;Virag Sagi-Kiss,&nbsp;Susana A Palma-Duran,&nbsp;Carol S Johnston,&nbsp;Diane M O'Brien,&nbsp;Natasha Tasevska","doi":"10.1158/1055-9965.EPI-21-1293","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-21-1293","url":null,"abstract":"<p><strong>Background: </strong>Twenty-four-hour urinary sucrose and fructose (24uSF) has been studied as a biomarker of total sugars intake in two feeding studies conducted in the United Kingdom (UK) and Arizona (AZ). We compare the biomarker performance in these populations, testing whether it meets the criteria for a predictive biomarker.</p><p><strong>Methods: </strong>The UK and AZ feeding studies included 13 and 98 participants, respectively, aged 18 to 70 years, consuming their usual diet under controlled conditions. Linear mixed models relating 24uSF to total sugars and personal characteristics were developed in each study and compared. The AZ calibrated biomarker equation was applied to generate biomarker-estimated total sugars intake in UK participants. Stability of the model across AZ study subpopulations was also examined.</p><p><strong>Results: </strong>Model coefficients were similar between the two studies [e.g., log(total sugars): UK 0.99, AZ 1.03, P = 0.67], as was the ratio of calibrated biomarker person-specific bias to between-person variance (UK 0.32, AZ 0.25, P = 0.68). The AZ equation estimated UK log(total sugar intakes) with mean squared prediction error of 0.27, similar to the AZ study estimate (0.28). Within the AZ study, the regression coefficients of log(total sugars) were similar across age, gender, and body mass index subpopulations.</p><p><strong>Conclusions: </strong>Similar model coefficients in the two studies and good prediction of UK sugar intakes by the AZ equation suggest that 24uSF meets the criteria for a predictive biomarker. Testing the biomarker performance in other populations is advisable.</p><p><strong>Impact: </strong>Applications of the 24uSF biomarker will enable improved assessment of the role of sugars intake in risk of chronic disease, including cancer. See related commentary by Prentice, p. 1151.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1227-1232"},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167729/pdf/nihms-1788163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40312960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Medicaid in Early Detection of Screening-Amenable Cancers.","authors":"Cathy J Bradley,&nbsp;Lindsay M Sabik,&nbsp;Julia Entwistle,&nbsp;Jennifer L Stevens,&nbsp;Lindsey Enewold,&nbsp;Joan L Warren","doi":"10.1158/1055-9965.EPI-21-1077","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-21-1077","url":null,"abstract":"<p><strong>Background: </strong>This study examines the association between Medicaid enrollment, including through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), and distant stage for three screening-amenable cancers: breast, cervical, and colorectal.</p><p><strong>Methods: </strong>We use the Surveillance, Epidemiology, and End Results Cancer Registry linked with Medicaid enrollment data to compare patients who were Medicaid insured with patients who were not Medicaid insured. We estimate the likelihood of distant stage at diagnosis using logistic regression.</p><p><strong>Results: </strong>Medicaid enrollment following diagnosis was associated with the highest likelihood of distant stage. Medicaid enrollment through NBCCEDP did not mitigate the likelihood of distant stage disease relative to Medicaid enrollment prior to diagnosis. Non-Hispanic Black patients had a greater likelihood of distant stage breast and colorectal cancer. Residing in higher socioeconomic areas was associated with a lower likelihood of distant stage breast cancer.</p><p><strong>Conclusions: </strong>Medicaid enrollment prior to diagnosis is associated with a lower likelihood of distant stage in screen amenable cancers but does not fully ameliorate disparities.</p><p><strong>Impact: </strong>Our study highlights the importance of health insurance coverage prior to diagnosis and demonstrates that while targeted programs such as the NBCCEDP provide critical access to screening, they are not a substitute for comprehensive insurance coverage.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1202-1208"},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167742/pdf/nihms-1788164.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Performance of the BD Onclarity Extended Genotyping Assay for the Management of Women Positive for Human Papillomavirus in Cervical Cancer Screening.","authors":"Karena D Volesky,&nbsp;Sindy Magnan,&nbsp;Marie-Hélène Mayrand,&nbsp;Sandra D Isidean,&nbsp;Mariam El-Zein,&nbsp;Emilie Comète,&nbsp;Eduardo L Franco,&nbsp;François Coutlée","doi":"10.1158/1055-9965.EPI-21-1082","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-21-1082","url":null,"abstract":"<p><strong>Background: </strong>Among women whose cervical specimens tested positive for high-risk human papillomaviruses (hrHPV) via the Hybrid Capture 2 assay in the Canadian Cervical Cancer Screening Trial (CCCaST), we assessed hrHPV genotype concordance between BD Onclarity HPV Assay and Roche's Linear Array, overall and stratified by hrHPV viral load. We also evaluated the performance of cytology, cytology combined with hrHPV genotyping (Onclarity assay) for HPV16/18 and non-HPV16/18 types, and hrHPV genotyping triage strategies for the detection of cervical intraepithelial neoplasia grade 2 or 3 and worse (CIN2+/CIN3+).</p><p><strong>Methods: </strong>Standard measures (expected agreement, agreement, and κ values) were used to compare Onclarity to the reference test, Linear Array. Twenty-four triage strategies were evaluated by calculating their sensitivities, specificities, and positive and negative predictive values for CIN2+ and CIN3+ detection.</p><p><strong>Results: </strong>Among 734 hrHPV+ samples tested, there was near perfect concordance irrespective of viral load between the Onclarity and Linear Array assays for the individual genotypes [human papillomaviruses (HPV) 16, 18, 31, 45, 51, 52] by Onclarity (κ values ranged from 0.92-0.98). Strategies with adequate specificity (>75%) and the highest sensitivities to detect CIN3+ among 617 women positive for hrHPV, were positivity to HPV16 and/or 31 (Sensitivity: 65.2%, Specificity: 76.9%) and HPV16 and/or 18 (Sensitivity: 58.7%, Specificity: 81.6%).</p><p><strong>Conclusions: </strong>While confirming the importance of HPV16, we found that HPV31 was comparable with HPV18 for the detection of CIN2/3+ in the triage of women positive for hrHPV.</p><p><strong>Impact: </strong>HPV31 may be an important genotype in the triage of women positive for hrHPV.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"851-857"},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39898600","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":"Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility.","authors":"Alessandro Testori,&nbsp;Zalman Vaksman,&nbsp;Sharon J Diskin,&nbsp;Hakon Hakonarson,&nbsp;Mario Capasso,&nbsp;Achille Iolascon,&nbsp;John M Maris,&nbsp;Marcella Devoto","doi":"10.1158/1055-9965.EPI-21-0782","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-21-0782","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease.</p><p><strong>Methods: </strong>We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs.</p><p><strong>Results: </strong>We confirmed the known neuroblastoma susceptibility gene BARD1 at genome-wide significance in the subset of high-risk cases. We also estimated local admixture across the autosomal genome in the AA cases and controls and detected a signal at 4q31.22 where cases show an increase in European ancestry. A region at 17p13.1 showed increased African ancestry in the subgroup of high-risk cases with respect to intermediate- and low-risk cases. Using results from our published European American (EA) genome-wide association study (GWAS), we found that a polygenic score that included all independent SNPs showed a highly significant association (P value = 1.8 × 10-73) and explained 19% of disease risk variance in an independent EA cohort. In contrast, the best fit polygenic score (P value = 3.2 × 10-11) in AAs included only 22 independent SNPs with association P value < 2.75 × 10-6 in the EA GWAS, and explained 2% of neuroblastoma risk variance. The significance of the polygenic score dropped rapidly with inclusion of additional SNPs.</p><p><strong>Conclusions: </strong>These findings suggest that several common variants contribute to risk of neuroblastoma in an ancestry-specific fashion.</p><p><strong>Impact: </strong>This work supports the need for GWAS to be performed in populations of all races and ethnicities.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"870-875"},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983590/pdf/nihms-1777897.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39898601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Night Shift Work, MTNR1B rs10830963 Polymorphism, and Prostate Cancer Risk: Findings from a Prospective, Population-Based Study.","authors":"Lulu Yang, Jie Chen, Hongliang Feng, Sizhi Ai, Yue Liu, Xinru Chen, Binbin Lei, Joey W Y Chan, Steven Wai Ho Chau, Lap Ah Tse, Amy Wing-Yin Ho, Chung Shun Ho, Yun Kwok Wing, Jihui Zhang","doi":"10.1158/1055-9965.EPI-21-1108","DOIUrl":"10.1158/1055-9965.EPI-21-1108","url":null,"abstract":"<p><strong>Background: </strong>The association between night shift work and prostate cancer is controversial. Evidence shows that genetic and environmental factors both contribute to the development of prostate cancer. It is well known that melatonin plays a protective role in prostate cancer. Melatonin receptor 1B gene (MTNR1B) rs10830963 influences the dynamics of melatonin secretion, and night shift work, which disrupts our internal circadian rhythms, also dysregulates the production of melatonin. Therefore, we aimed to examine the interaction between night shift work and rs10830963 polymorphism on prostate cancer.</p><p><strong>Methods: </strong>This is a prospective cohort study based on UK Biobank that included 133,416 employed male participants. Exposures included night shift work and rs10830963 polymorphism. The primary outcome was the incidence of prostate cancer. Cox regression analysis was used to estimate the association of night shift work and MTNR1B rs10830963 with prostate cancer.</p><p><strong>Results: </strong>A significant interaction was found between night shift work and MTNR1B rs10830963 on the incidence of prostate cancer (P = 0.009). Among non-night shift workers, rs10830963 polymorphism was not significantly associated with the risk of prostate cancer. Among night shift workers, compared with CC carriers, GC carriers had a significantly lower risk of prostate cancer [HR: 0.69; 95% confidence interval (CI): 0.51-0.93], and similar associations were more evident for GG carriers (HR: 0.33; 95% CI: 0.15-0.75).</p><p><strong>Conclusions: </strong>Compared with MTNR1B rs10830963 CC, carrying allele G may reduce the risk of prostate cancer when exposed to night shift work.</p><p><strong>Impact: </strong>These results suggest that rs10830963 G carriers may have a lower risk of prostate cancer when taking night shifts.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"728-735"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39847888","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":"Too Good to Be True? Evaluation of Colonoscopy Sensitivity Assumptions Used in Policy Models.","authors":"Carolyn M Rutter,&nbsp;Pedro Nascimento de Lima,&nbsp;Jeffrey K Lee,&nbsp;Jonathan Ozik","doi":"10.1158/1055-9965.EPI-21-1001","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-21-1001","url":null,"abstract":"<p><strong>Background: </strong>Models can help guide colorectal cancer screening policy. Although models are carefully calibrated and validated, there is less scrutiny of assumptions about test performance.</p><p><strong>Methods: </strong>We examined the validity of the CRC-SPIN model and colonoscopy sensitivity assumptions. Standard sensitivity assumptions, consistent with published decision analyses, assume sensitivity equal to 0.75 for diminutive adenomas (<6 mm), 0.85 for small adenomas (6-10 mm), 0.95 for large adenomas (≥10 mm), and 0.95 for preclinical cancer. We also selected adenoma sensitivity that resulted in more accurate predictions. Targets were drawn from the Wheat Bran Fiber study. We examined how well the model predicted outcomes measured over a three-year follow-up period, including the number of adenomas detected, the size of the largest adenoma detected, and incident colorectal cancer.</p><p><strong>Results: </strong>Using standard sensitivity assumptions, the model predicted adenoma prevalence that was too low (42.5% versus 48.9% observed, with 95% confidence interval 45.3%-50.7%) and detection of too few large adenomas (5.1% versus 14.% observed, with 95% confidence interval 11.8%-17.4%). Predictions were close to targets when we set sensitivities to 0.20 for diminutive adenomas, 0.60 for small adenomas, 0.80 for 10- to 20-mm adenomas, and 0.98 for adenomas 20 mm and larger.</p><p><strong>Conclusions: </strong>Colonoscopy may be less accurate than currently assumed, especially for diminutive adenomas. Alternatively, the CRC-SPIN model may not accurately simulate onset and progression of adenomas in higher-risk populations.</p><p><strong>Impact: </strong>Misspecification of either colonoscopy sensitivity or disease progression in high-risk populations may affect the predicted effectiveness of colorectal cancer screening. When possible, decision analyses used to inform policy should address these uncertainties.See related commentary by Etzioni and Lange, p. 702.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"775-782"},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983491/pdf/nihms-1762910.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39602109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}