bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 3A from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

Amplification plot demonstrating the successful HPV amplification and enrichment obtained with dual sequence capture. Delta Ct values for HeLa (pink/red) and CSCC7 (purples) were 14.88 and 12.66, respectively. Based on an estimated efficiency for the assay, the approximate fold enrichment was greater than 1700.
Suppl_Figure1 from HCV Eradication in Primary or Secondary Prevention Optimizes Hepatocellular Carcinoma Curative Management
Authors: Nahon Pierre , Layese Richard , Cagnot Carole , Asselah Tarik , Guyader Dominique , Pol Stanislas , Pageaux Georges-Philippe , De Lédinghen Victor , Ouzan Denis , Zoulim Fabien , Audureau Etienne
Published: April 2023

Suppl Figure 1
Supplement Table 3 from A Calcium-Rich Multimineral Intervention to Modulate Colonic Microbial Communities and Metabolomic Profiles in Humans: Results from a 90-Day Trial
Authors: Aslam Muhammad N. , Bassis Christine M. , Bergin Ingrid L. , Knuver Karsten , Zick Suzanna M. , Sen Ananda , Turgeon D. Kim , Varani James
Published: April 2023

The distribution of Phyla based on sample type (all samples).
Supplementary Table 1d from Risk Prediction Models for Colorectal Cancer: A Systematic Review
Authors: Usher-Smith Juliet A. , Walter Fiona M. , Emery Jon D. , Win Aung K. , Griffin Simon J.
Published: April 2023

Details of development of models from other methods.
Supplementary Table 2 from Physical Activity and Long-term Quality of Life among Colorectal Cancer Survivors—A Population-based Prospective Study
Authors: Eyl Ruth Elisa , Koch-Gallenkamp Lena , Jansen Lina , Walter Viola , Carr Prudence R. , Hoffmeister Michael , Chang-Claude Jenny , Brenner Hermann , Arndt Volker
Published: April 2023

Supplementary Table 2
supplementary figure S3 from Noninvasive Molecular Screening for Oral Precancer in Fanconi Anemia Patients
Authors: Smetsers Stephanie E. , Velleuer Eunike , Dietrich Ralf , Wu Thijs , Brink Arjen , Buijze Marijke , Deeg Dorly J.H. , Soulier Jean , Leemans C. René , Braakhuis Boudewijn J.M. , Brakenhoff Ruud H.
Published: April 2023

Figure S3. Visible lesions in non-transplanted FA patients. Visible lesions were found in 27 of 110 patients (25%) with follow-up. Five patients with visible lesions (4 with LOH, 1 without LOH) developed HNSCC.
Supplementary Figure 4 from HIST1H2BB and MAGI2 Methylation and Somatic Mutations as Precision Medicine Biomarkers for Diagnosis and Prognosis of High-grade Serous Ovarian Cancer
Authors: Valle Blanca L. , Rodriguez-Torres Sebastian , Kuhn Elisabetta , Díaz-Montes Teresa , Parrilla-Castellar Edgardo , Lawson Fahcina P. , Folawiyo Oluwasina , Ili-Gangas Carmen , Brebi-Mieville Priscilla , Eshleman James R. , Herman James , Shih Ie-Ming , Sidransky David , Guerrero-Preston Rafael
Published: April 2023

Supplementary Figure 4
Supplementary Data from Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Patients with Colon Adenoma: A Randomized Clinical Trial
Authors: Vermandere Kelly , Bostick Roberd M. , Tran Hao Q. , Gewirtz Andrew T. , Barry Elizabeth L. , Rutherford Robin E. , Seabrook March E. , Fedirko Veronika
Published: April 2023

Supplementary Tables
Supplementary Table from Reversing the Genomic, Epigenetic, and Triple-Negative Breast Cancer–Enhancing Effects of Obesity
Authors: Bowers Laura W. , Doerstling Steven S. , Shamsunder Meghana G. , Lineberger Claire G. , Rossi Emily L. , Montgomery Stephanie A. , Coleman Michael F. , Gong Weida , Parker Joel S. , Howell Anthony , Harvie Michelle , Hursting Stephen D.
Published: April 2023

Supplementary Table from Reversing the Genomic, Epigenetic, and Triple-Negative Breast Cancer–Enhancing Effects of Obesity
Supplementary Figures from Chemoprevention of Azoxymethane-induced Colon Carcinogenesis by Delta-Tocotrienol
Authors: Husain Kazim , Zhang Anying , Shivers Steve , Davis-Yadley Ashley , Coppola Domenico , Yang Chung S. , Malafa Mokenge P.
Published: April 2023

This PowerPoint contains supplementary figures 1-5.
Supplementary Table S2 from The Quality of Pap Smears from the Brazilian Cervical Cancer Screening Program According to the Human Development Index
Authors: Costa Ricardo Filipe Alves , Longatto-Filho Adhemar , de Lima Vazquez Fabiana , Pinheiro Céline , Zeferino Luiz Carlos , Fregnani José Humberto Tavares Guerreiro
Published: April 2023

Supplementary Table S2 shows values of the cervical cancer screening program quality indicators in the target age (25-64 years) according to Brazilian Municipal Human Development Index, from 2006 to 2014.
Table S1-S7 from Serum Levels of Androgens, Estrogens, and Sex Hormone Binding Globulin and Risk of Primary Gastric Cancer in Chinese Men: A Nested Case–Control Study
Authors: Zhu Zhikai , Chen Yingxi , Ren Jiansong , Dawsey Sanford M. , Yin Jian , Freedman Neal D. , Fan Jin-Hu , Taylor Philip R. , Liu Yuanli , Qiao You-Lin , Abnet Christian C.
Published: April 2023

Table S1 shows the information of Linxian Nutrition Intervention Trials; Table S2 shows the correlation between sex hormones and SHBG; Table S3-S6 show the ORs by age, alcohol drinking, smoking, follow-up time subgroups; Table S7 shows that the ORs in General Population Trial.
Supplemental Table 2. Complete RNAseq data from A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology
Authors: Fan Yang-Yi , Callaway Evelyn , M. Monk Jennifer , S. Goldsby Jennifer , Yang Peiying , Vincent Logan , S. Chapkin Robert
Published: April 2023

Complete RNAseq data set.
Supplemental Table 1. Dietary fatty acid composition from A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology
Authors: Fan Yang-Yi , Callaway Evelyn , M. Monk Jennifer , S. Goldsby Jennifer , Yang Peiying , Vincent Logan , S. Chapkin Robert
Published: April 2023

Detail dietary FA composition.
Supplemental Figure 1. Representative images of aberrant crypts stained with methylene blue. from A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology
Authors: Fan Yang-Yi , Callaway Evelyn , M. Monk Jennifer , S. Goldsby Jennifer , Yang Peiying , Vincent Logan , S. Chapkin Robert
Published: April 2023

A. Three key criteria to define aberrant crypt include: (1) the area occupied by the crypt and its pericryptal zone is greater than the surrounding normal crypts; (2) irregular shape of the luminal opening; and (3) the epithelial lining is thicker and darker than that of the surrounding crypt. B. Images of ACF with various aberrant crypts/focus (40x magnification).
Supplementary Data from Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial
Authors: Yan Mabel K. , Orchard Suzanne G. , Adler Nikki R. , Wolfe Rory , McLean Catriona , Rodriguez Luz María. , Woods Robyn L. , Gibbs Peter , Chan Andrew T. , Haydon Andrew , Mar Victoria J.
Published: April 2023

Supplementary Data from Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial
Supplementary Data Table S3 from Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng
Published: April 2023

Phenotype3.insulin
Supplementary Table from Colonoscopy Findings in FIT+ and mt-sDNA+ Patients versus in Colonoscopy-only Patients: New Hampshire Colonoscopy Registry Data
Authors: Anderson Joseph C. , Robinson Christina M. , Hisey William , Limburg Paul J. , Butterly Lynn F.
Published: April 2023

Supplementary Table from Colonoscopy Findings in FIT+ and mt-sDNA+ Patients versus in Colonoscopy-only Patients: New Hampshire Colonoscopy Registry Data
Supplementary Data Table S1 from Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng
Published: April 2023

Allele frequency
Supplemental Tables from Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated (ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers
Authors: Hall Michael J. , Bernhisel Ryan , Hughes Elisha , Larson Katie , Rosenthal Eric T. , Singh Nanda A. , Lancaster Johnathan M. , Kurian Allison W.
Published: April 2023

Supplemental Tables 1-3
Supplementary Data Figure S3 from Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng
Published: April 2023

Manhattan plot
Supplementary Data Figure S2 from Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng
Published: April 2023

Flow diagram of analytic cohort
Supplementary Data Figure S1 from Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng
Published: April 2023

Diagrams of pathways of SNPs
Supplementary Data from Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study
Authors: Fabian Carol J. , Nye Lauren , Powers Kandy R. , Nydegger Jennifer L. , Kreutzjans Amy L. , Phillips Teresa A. , Metheny Trina , Winblad Onalisa , Zalles Carola M. , Hagan Christy R. , Goodman Merit L. , Gajewski Byron J. , Koestler Devin C. , Chalise Prabhakar , Kimler Bruce F.
Published: April 2023

Supplementary Tables 1-3
Figure S1 from Addressing Disparities in Cancer Screening among U.S. Immigrants: Progress and Opportunities
Authors: Fang Carolyn Y. , Ragin Camille C.
Published: April 2023

Supplementary Figure 1 -PRISMA Flow diagram
Table S2 from Interventions to Reduce Future Cancer Incidence from Diesel Engine Exhaust: What Might Work?
Authors: Carey Renee N. , Fritschi Lin , Driscoll Timothy R. , Peters Susan , Glass Deborah C. , Benke Geza , Reid Alison
Published: April 2023

Sensitivity Analysis - Lung
Supplementary Table 5 from Do Aspirin and Other NSAIDs Confer a Survival Benefit in Men Diagnosed with Prostate Cancer? A Pooled Analysis of NIH-AARP and PLCO Cohorts
Authors: Zhou Cindy Ke , Daugherty Sarah E. , Liao Linda M. , Freedman Neal D. , Abnet Christian C. , Pfeiffer Ruth , Cook Michael B.
Published: April 2023

Frequency of pre-diagnostic NSAID use in relation to mortality within the strata of tumor stage (localized vs. regional/distant).
Figure S3 from In Silico Systems Biology Analysis of Variants of Uncertain Significance in Lynch Syndrome Supports the Prioritization of Functional Molecular Validation
Authors: Borras Ester , Chang Kyle , Pande Mala , Cuddy Amanda , Bosch Jennifer L. , Bannon Sarah A. , Mork Maureen E. , Rodriguez-Bigas Miguel A. , Taggart Melissa W. , Lynch Patrick M. , You Y. Nancy , Vilar Eduardo
Published: April 2023

Supplementary Figure S3. Validation analysis performed in variants already re-classified as InSIGHT Class 1 and Class 5; A. Proportions of results obtained from different in silico prediction tools at the RNA level; B. Prediction results at the RNA level stratified by InSIGHT class; C. Proportion of results from different prediction tools at the protein level; D. Prediction results at the DNA level stratified by InSIGHT class; E. Final prior-classification using RNA and protein in silico analysis; F. Final prior-classification using RNA and protein in silico analysis stratified by InSIGHT class 5.
Supplementary Tables 1 and 2 from Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial
Authors: Brown Justin C. , Zhang Sui , Ligibel Jennifer A. , Irwin Melinda L. , Jones Lee W. , Campbell Nancy , Pollak Michael N. , Sorrentino Alexandra , Cartmel Brenda , Harrigan Maura , Tolaney Sara M. , Winer Eric P. , Ng Kimmie , Abrams Thomas A. , Sanft Tara , Douglas Pamela S. , Hu Frank B. , Fuchs Charles S. , Meyerhardt Jeffrey A.
Published: April 2023

Supplementary Tables 1 and 2
Supplementary Table S2 from Chemopreventive Effect of Cinnamon and Its Bioactive Compounds in a Rat Model of Premalignant Prostate Carcinogenesis
Authors: Gopalakrishnan Srividya , Dhaware Mahamaya , Sudharma Athira Anilkumar , Mullapudi Surekha Venkata , Siginam Siva Ramakrishna , Gogulothu Ramesh , Mir Irfan Ahmad , Ismail Ayesha
Published: April 2023

Supplementary Table S2: Hematological and bone related parameters in the different groups of rats
Supplementary Figure S1 from Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort
Authors: Sherman Mark E. , Vierkant Robert A. , Masters Matthew , Radisky Derek C. , Winham Stacey J. , Degnim Amy C. , Vachon Celine M. , Patel Alpa V. , Teras Lauren R.
Published: April 2023

Supplementary Figure S1: Pills per month modeled using a restricted cubic spline in Cox proportional hazards regression analysis accounting for age as a stratification variable and adjusting for history of benign breast disease, race, weight gain as an adult, highest educational level achieved, oral contraceptive use, smoking status, age at menarche, age at menopause, use of hormone replacements, family history of breast cancer, parity, age at first birth, history of undergoing mammograms, history of hypertension, history of diabetes, history of cardiovascular disease, daily caloric intake and alcohol consumption.
Supplementary Methods S1 from Estrogen-DNA Adducts and Breast Cancer Risk in Premenopausal Asian Women
Authors: Lin Ching-Hung , Zahid Muhammad , Kuo Wen-Hung , Hu Fu-Chang , Wang Ming-Yang , Chen I-Chun , Beseler Cheryl L. , Mondal Bodhisattwa , Lu Yen-Shen , Rogan Eleanor G. , Cheng Ann-Lii
Published: April 2023

Supplementary Methods S1 describes the statistical analysis in detail.
Supplementary Table S2 from Prospective Study of Avocado Consumption and Cancer Risk in U.S. Men and Women
Authors: Ericsson Caroline I. , Pacheco Lorena S. , Romanos-Nanclares Andrea , Ecsedy Ethan , Giovannucci Edward L. , Eliassen A. Heather , Mucci Lorelei A. , Fu Benjamin C.
Published: April 2023

Supplementary Table S2 shows avocado consumption and risk of total cancer stratified by age, BMI, and AHEI.
Supplementary Table S1 from Prospective Study of Avocado Consumption and Cancer Risk in U.S. Men and Women
Authors: Ericsson Caroline I. , Pacheco Lorena S. , Romanos-Nanclares Andrea , Ecsedy Ethan , Giovannucci Edward L. , Eliassen A. Heather , Mucci Lorelei A. , Fu Benjamin C.
Published: April 2023

Supplementary Table S1 shows associations of avocado consumption and risk of cancer excluding current smokers, with similar results as the overall cohort.
Supplementary Table S2 from Trends and Factors Associated with Fecal Occult Blood Test Utilization among Hispanic Adults in Puerto Rico and the United States: BRFSS 2012–2020
Authors: Castaneda-Avila Maira A. , Oyinbo Atinuke G. , Epstein Mara M. , Ortiz-Ortiz Karen J. , Tortolero-Luna Guillermo , Lapane Kate L.
Published: April 2023

Supplementary Table S2 shows factors associated with blood stool test use for colorectal screening among Hispanic adults living in Puerto Rico
Supplementary Figure S1 from Trends and Factors Associated with Fecal Occult Blood Test Utilization among Hispanic Adults in Puerto Rico and the United States: BRFSS 2012–2020
Authors: Castaneda-Avila Maira A. , Oyinbo Atinuke G. , Epstein Mara M. , Ortiz-Ortiz Karen J. , Tortolero-Luna Guillermo , Lapane Kate L.
Published: April 2023

Supplementary Figure S1 shows the sample selection
Supplementary Table S2 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: April 2023

Supplementary Table S2 shows the list of metabolites that were examined among control, LPS, and LPS + SAHA groups after 3 and 24 h treatments.
Supplementary Table S1 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: April 2023

Supplementary Table S1 shows the primer sequences of the genes used in the qPCR assay.
Supplementary Materials 3 from Determinants of Lung Cancer Screening in a Minnesota Urban Indigenous Community: A Community-Based, Participatory, Action-Oriented Study
Authors: Anderson Madison D. , Pickner Wyatt J. , Begnaud Abbie
Published: April 2023

Supplementary Materials 3: Lung Cancer Brochure developed from this work
Supplementary Table S4 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in U.S. Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: April 2023

Supplementary Table S4: NRI and IDI of the risk prediction models for high-risk SPs.
Supplementary Table S5 from Validation of an Abridged Breast Cancer Risk Prediction Model for the General Population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: April 2023

Supplementary Table S5 shows the five-year vs full-lifetime risk classification for 313-SNP BRISK for unaffected and affected women
Supplementary Table S2 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in U.S. Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: April 2023

Supplementary Table S2: Associations of the included predictors with the risk of high-risk SPs by sex.
Supplementary Table S3 from Validation of an Abridged Breast Cancer Risk Prediction Model for the General Population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: April 2023

Supplementary Table S3 shows the characteristics of affected and unaffected participants
Supplemental Figure 1 from Breastfeeding and Mammographic Breast Density: A Cross-sectional Study
Authors: Getz Kayla R. , Adedokun Babatunde , Xu Shuai , Toriola Adetunji T.
Published: April 2023

Supplemental Figure 1: Flowchart displaying how we arrived at the final analytic sample. Among the women recruited to the study, 127 were missing breastfeeding duration and 32 were missing values for all of the MBD measures. An additional 18 participants were missing values for one of the confounding variables; 11 women were missing age at menarche, 1 woman was missing BMI and 6 women were missing information about family history of breast cancer.
Data from Trends and Factors Associated with Fecal Occult Blood Test Utilization among Hispanic Adults in Puerto Rico and the United States: BRFSS 2012–2020
Authors: Castaneda-Avila Maira A. , Oyinbo Atinuke G. , Epstein Mara M. , Ortiz-Ortiz Karen J. , Tortolero-Luna Guillermo , Lapane Kate L.
Published: April 2023

Abstract
Identifying factors associated with colorectal cancer screening utilization is important to guide colorectal cancer prevention and control programs. We evaluated trends and factors associated with previous-year fecal occult blood test (FOBT) use among Hispanic adults living in Puerto Rico and the U.S. mainland. Using data from the Behavioral Risk Factor Surveillance System (2012–2020), trends in FOBT use were analyzed using joinpoint regression to estimate annual percentage change (APC). Logistic regression stratified by location identified factors associated with FOBT use. FOBT was more common among Hispanic adults ages 50 to 75 years living in Puerto Rico than in the U.S. mainland [Puerto Rico: 20.5%[2012] to 45.6%[2020], APC = 11.4%; U.S. mainland: 9.9%[2012] to 16.7%[2020], APC = 5.9%]. Factors inversely associated with FOBT use were similar in Puerto Rico and the U.S. mainland, including lack of health insurance, not having a personal doctor, having a checkup >12 months ago, and not being able to see a doctor due to cost, as were factors associated with higher FOBT use, including older age, retirement, or having two or more chronic diseases. Among Hispanics living in the U.S. mainland, lack of exercise and less education were inversely associated with FOBT. Factors related to poor access to healthcare were associated with lower use of FOBT among Hispanics. Efforts to improve colorectal cancer screening in Hispanics are necessary to address health disparities across the colorectal cancer care continuum.
Prevention Relevance:
Colorectal cancer screening reduces cancer incidence and mortality. All screening modalities, including less invasive FOBT tests, are underutilized, especially in non-White and low-income populations. Evaluation of trends and factors associated with the increase in the use of colorectal cancer screening can inform programs to address the lack of screening among racial minorities.
Data from Prospective Study of Avocado Consumption and Cancer Risk in U.S. Men and Women
Authors: Ericsson Caroline I. , Pacheco Lorena S. , Romanos-Nanclares Andrea , Ecsedy Ethan , Giovannucci Edward L. , Eliassen A. Heather , Mucci Lorelei A. , Fu Benjamin C.
Published: April 2023

Abstract
Avocados contain nutrients and phytochemicals that make it promising for cancer prevention, and chemopreventive properties have been demonstrated in prior studies. Prospective studies on avocado consumption and cancer risk have yet to be conducted. This study included data from 45,289 men in the Health Professionals Follow-Up Study (HPFS, 1986–2016) and 67,039 women in the Nurses’ Health Study (NHS, 1986–2014). Avocado consumption was assessed using validated food frequency questionnaires every 4 years. Cox proportional hazards models calculated multivariable HRs and 95% confidence intervals (CI) for associations between avocado consumption and risk of total and site-specific cancers in each cohort. In HPFS, consumption of ≥1 weekly serving of avocados was associated with decreased risk of total (HR, 0.85; 95% CI, 0.80–0.91), colorectal (HR, 0.71; 95% CI, 0.59–0.85), lung (HR, 0.71; 95% CI, 0.57–0.90), and bladder cancer (HR, 0.72; 95% CI, 0.57–0.90). In NHS, avocado consumption was associated with increased risk of breast cancer (HR, 1.21; 95% CI, 1.07–1.37). No associations were observed between avocado consumption and risk of total cancer (HR, 1.06; 95% CI, 0.98–1.14) or other site-specific cancers in NHS. Considering the surprising breast cancer finding, analyses were repeated using data from 93,230 younger women in the parallel NHSII (1991–2017). In NHSII, avocado consumption was not associated with breast cancer risk (HR, 0.93; 95% CI, 0.76–1.13). Overall, avocado consumption may be associated with reduced risk of total and some site-specific cancers in men. The positive association with breast cancer risk in NHS was not seen in the younger NHSII.
Prevention Relevance:
The results of this prospective study suggest that avocado consumption may be associated with decreased risk of total and some site-specific cancers in men.

See related Spotlight, p. 187
Data from Simplifying the Energy Balance Message for Breast Cancer Prevention
Authors: Fabian Carol J.
Published: April 2023

Abstract
Simple prevention messages based on understandable biologic principles are likely to be adopted. The long-held premise that postmenopausal obesity elevates, but premenopausal obesity reduces, risk for breast cancer is confusing to the public. Furthermore, decades of positive energy balance may be difficult to suddenly reverse at the time of the menopause. In this issue (beginning on page 583), Cecchini et al. suggest that obesity may also be a risk factor for pre-menopausal women 35 and older who have additional risk factors for breast cancer. Although the relative impact of dysregulated energy metabolism depends on many factors including age, hormonal milieu, and competing risk factors, as well as how it is measured, avoiding weight gain after age 30 is increasingly being recognized as a simple way to reduce risk of breast cancer. Cancer Prev Res; 5(4); 511–4. ©2012 AACR.
Data from Strawberry Fields Forever?
Authors: Suh Nanjoo , Pezzuto John M.
Published: April 2023

Abstract
On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. Cancer Prev Res; 5(1); 30–33. ©2012 AACR.
Data from Grape Seeds: Ripe for Cancer Chemoprevention
Authors: Katiyar Santosh K. , Athar Mohammad
Published: April 2023

Abstract
A wide variety of phytochemicals, mostly flavonoids or polyphenolics, have been shown to possess anticarcinogenic activities. Among these are the grape seed proanthocyanidins (GSPs), which are the active ingredients of grape seed extract (GSE). Substantial in vitro and preclinical in vivo studies have shown the chemopreventive efficacy of GSPs against various forms of cancers in different tumor models. In this issue of the journal, Derry and colleagues show that administration of GSE in the diet reduces azoxymethane-induced colon carcinogenesis in an A/J mouse model. The results of this innovative and comprehensive study indicate that inhibition of azoxymethane-induced colon cancer by dietary GSE is mediated through the induction of apoptosis that is associated with alterations in microRNA (miRNA) and cytokine expression profiles as well as β-catenin signaling. Notably, the demonstration that miRNA expression is affected by dietary GSE suggests a novel underlying mechanism for the chemopreventive action of GSE in colon cancer and, potentially, other cancers. Cancer Prev Res; 6(7); 617–21. ©2013 AACR.
Data from The Chemopreventive Efficacies of Nonsteroidal Anti-inflammatory Drugs: The Relationship of Short-term Biomarkers to Long-term Skin Tumor Outcome
Authors: Mikulec Carol D. , Rundhaug Joyce E. , Simper Melissa S. , Lubet Ronald A. , Fischer Susan M.
Published: April 2023

Abstract
The ultraviolet B (UVB) component of sunlight, which causes DNA damage and inflammation, is the major cause of nonmelanoma skin cancer (NMSC), the most prevalent of all cancers. Nonsteroidal anti-inflammatory drugs (NSAID) and coxibs have been shown to be effective chemoprevention agents in multiple preclinical trials, including NMSC, colon, and urinary bladder cancer. NSAIDs, however, cause gastrointestinal irritation, which led to the recent development of nitric oxide (NO) derivatives that may partially ameliorate this toxicity. This study compared the efficacy of several NSAIDs and NO-NSAIDs on UV-induced NMSC in SKH-1 hairless mice and determined whether various short-term biomarkers were predictive of long-term tumor outcome with these agents. Naproxen at 100 (P = 0.05) and 400 ppm (P < 0.01) in the diet reduced tumor multiplicity by 26% and 63%, respectively. The NO-naproxen at slightly lower molar doses shows similar activities. Aspirin at 60 or 750 ppm in the diet reduced tumor multiplicity by 19% and 50%, whereas the equivalent doses (108 and 1,350 ppm) were slightly less effective. Sulindac at 25 and 150 ppm in the diet, doses far below the human equivalent dose was the most potent NSAID with reductions of 50% and 94%, respectively. In testing short-term biomarkers, we found that agents that reduce UV-induced prostaglandin E2 synthesis and/or inhibit UV-induced keratinocyte proliferation yielded long-term tumor efficacy. Cancer Prev Res; 6(7); 675–85. ©2013 AACR.
Data from PI3K-AKT Signaling Is a Downstream Effector of Retinoid Prevention of Murine Basal Cell Carcinogenesis
Authors: So Po-Lin , Wang Grace Y. , Wang Kevin , Chuang Mindy , Chiueh Venice Calinisan , Kenny Paraic A. , Epstein Ervin H.
Published: April 2023

Abstract
Basal cell carcinoma (BCC) is the most common human cancer. We have demonstrated previously that topical application of the retinoid prodrug tazarotene profoundly inhibits murine BCC carcinogenesis via retinoic acid receptor γ–mediated regulation of tumor cell transcription. Because topical retinoids can cause adverse cutaneous effects and because tumors can develop resistance to retinoids, we have investigated mechanisms downstream of tazarotene's antitumor effect in this model. Specifically we have used (i) global expression profiling to identify and (ii) functional cell-based assays to validate the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway as a downstream target pathway of tazarotene's action. Crucially, we have demonstrated that pharmacologic inhibition of this downstream pathway profoundly reduces murine BCC cell proliferation and tumorigenesis both in vitro and in vivo. These data identify PI3K/AKT/mTOR signaling as a highly attractive target for BCC chemoprevention and indicate more generally that this pathway may be, in some contexts, an important mediator of retinoid anticancer effects. Cancer Prev Res; 7(4); 407–17. ©2014 AACR.
Data from Profiling Lipoxygenase Metabolism in Specific Steps of Colorectal Tumorigenesis
Authors: Shureiqi Imad , Chen Dongning , Day R. Sue , Zuo Xiangsheng , Hochman Fredric Lyone , Ross William A. , Cole Rhonda A. , Moy Ofie , Morris Jeffrey S. , Xiao Lianchun , Newman Robert A. , Yang Peiying , Lippman Scott M.
Published: April 2023

Abstract
Lipoxygenases (LOX) are key enzymes for the oxidative metabolism of polyunsaturated fatty acids into biologically active products. Clinical data on comparative levels of various LOX products in tumorigenesis are lacking. Therefore, we examined the profiles of several LOX products (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2) by liquid chromatography/tandem mass spectrometry in the major steps of colorectal tumorigenesis (normal, polyp, and cancer) in a clinical study of 125 subjects (49 with normal colon, 36 with colorectal polyps, and 40 with colorectal cancer) who underwent prospective colorectal biopsies to control for various potential confounding factors (e.g., diet, medications). Mean 13-hydroxyoctadecadienoic acid (13-HODE) levels were significantly higher in normal colon [mean, 36.11 ng/mg protein; 95% confidence interval (95% CI), 31.56-40.67] than in paired colorectal cancer mucosa (mean, 27.01 ng/mg protein; 95% CI, 22.00-32.02; P = 0.0002), and in normal colon (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.34) than in paired colorectal polyp mucosa (mean, 28.07 ng/mg protein; 95% CI, 23.66-32.48; P < 0.001). Mean 13-HODE levels, however, were similar between the left (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.35) and the right normal colon (mean, 32.46 ng/mg protein; 95% CI, 27.95-36.98; P = 0.09). No significant differences with regard to 12- or 15-hydroxyeicosatetraenoic acid or leukotriene B4 levels were detected between normal, polyp, and cancer mucosae. 15-LOX-1 inhibited interleukin-1β expression. This study establishes that reduced 13-HODE levels are a specific alteration in the LOX product profile associated with human colorectal tumorigenesis. Cancer Prev Res; 3(7); 829–38. ©2010 AACR.
Data from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
Authors: Irons Robert , Tsuji Petra A. , Carlson Bradley A. , Ouyang Ping , Yoo Min-Hyuk , Xu Xue-Ming , Hatfield Dolph L. , Gladyshev Vadim N. , Davis Cindy D.
Published: April 2023

Abstract
Selenium has cancer-preventive activity that is mediated, in part, through selenoproteins. The role of the 15-kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with short hairpin RNA constructs targeting Sep15. Metabolic 75Se labeling and Northern and Western blot analyses revealed that >90% of Sep15 was downregulated. Growth of the resulting Sep15-deficient CT26 cells was reduced (P < 0.01), and cells formed significantly (P < 0.001) fewer colonies in soft agar compared with control CT26 cells. Whereas most (14 of 15) BALB/c mice injected with control cells developed tumors, few (3 of 30) mice injected with Sep15-deficient cells developed tumors (P < 0.0001). The ability to form pulmonary metastases had similar results. Mice injected with the plasmid-transfected control cells had >250 lung metastases per mouse; however, mice injected with cells with downregulation of Sep15 only had 7.8 ± 5.4 metastases. To investigate molecular targets affected by Sep15 status, gene expression patterns between control and knockdown CT26 cells were compared. Ingenuity Pathways Analysis was used to analyze the 1,045 genes that were significantly (P < 0.001) affected by Sep15 deficiency. The highest-scored biological functions were cancer and cellular growth and proliferation. Consistent with these observations, subsequent analyses revealed a G2-M cell cycle arrest in cells with targeted downregulation of Sep15. In contrast to CT26 cells, Sep15-targeted downregulation in Lewis lung carcinoma (LLC1) cells did not affect anchorage-dependent or anchorage-independent cell growth. These data suggest tissue specificity in the cancer-protective effects of Sep15 downregulation, which are mediated, at least in part, by influencing the cell cycle. Cancer Prev Res; 3(5); 630–9. ©2010 AACR.
Data from Chemoprevention Activity of 25-Hydroxyvitamin D in the MMTV-PyMT Mouse Model of Breast Cancer
Authors: Rossdeutscher Lionel , Li Jiarong , Luco Aimée-Lee , Fadhil Ibtihal , Ochietti Benoit , Camirand Anne , Huang Dao Chao , Reinhardt Timothy A. , Muller William , Kremer Richard
Published: April 2023

Abstract
Development of oncologic conditions is often accompanied by inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Because current effective vitamin D analogues, including the naturally occurring active metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D), frequently cause hypercalcemia at pharmacologic doses, the development of safer molecules for clinical chemopreventive use is essential. This study examines whether exogenously supplied prohormone 25-hydroxycholecalciferol (25(OH)D) can delay tumor progression in vivo without hypercalcemic effects. A low vitamin D diet (25 IU/kg) in the non-immunodeficient MMTV-PyMT mouse model of metastatic breast cancer revealed a significant acceleration of mammary neoplasia compared with normal diet (1,000 IU/kg). Systemic perfusion of MMTV-PyMT mice with 25(OH)D or 1,25(OH)2D delayed tumor appearance and significantly decreased lung metastasis, and both metabolites reduced Ki-67, cyclin D1, and ErbB2 levels in tumors. Perfusion with 25(OH)D caused a 50% raise in tumor 1,25(OH)2D levels, indicating good tumor penetration and effective activation. Importantly, in contrast with 1,25(OH)2D, perfusion with 25(OH)D did not cause hypercalcemia. In vitro treatment of cultured MMTV-PyMT mammary tumor cells with 25(OH)D inhibited proliferation, confirming local activation of the prohormone in this system. This study provides an in vivo demonstration in a non-immunodeficient model of spontaneous breast cancer that exogenous 25(OH)D delays neoplasia, tumor growth, and metastasis, and that its chemoprevention efficacy is not accompanied by hypercalcemia. Cancer Prev Res; 8(2); 120–8. ©2014 AACR.
Data from C-reactive Protein and Risk of Colorectal Adenomas or Serrated Polyps: A Prospective Study
Authors: Crockett Seth D. , Mott Leila A. , Barry Elizabeth L. , Figueiredo Jane C. , Burke Carol A. , Baxter Gwen J. , Sandler Robert S. , Baron John A.
Published: April 2023

Abstract
Serum C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Because there is a well-recognized relationship between local inflammation and colorectal cancer, we aimed to evaluate whether serum CRP levels were associated with the occurrence of colorectal adenomas and serrated polyps using data from a large adenoma prevention trial. A total of 930 participants with a history of colorectal adenomas were enrolled in a randomized trial of calcium supplementation (1,200 mg/day) for the prevention of colorectal adenomas. Outcomes in this analysis are metachronous adenomas (and advanced neoplasms specifically), and serrated polyps at follow-up colonoscopy. High-sensitivity CRP levels were measured 1 year following baseline colonoscopy. Multivariate analysis was performed to estimate risk ratios (RR) using Poisson regression, controlling for potential confounders. We measured serum CRP levels in 689 participants (mean CRP, 3.62 ± 5.72 mg/L). There was no difference in CRP levels with respect to calcium versus placebo treatment assignment (P = 0.99). After adjustment for potential confounders, we found no association between CRP level and risk of recurrent adenoma or advanced lesion [quartile 4 vs. quartile 1: RR, 95% confidence interval (CI) = 0.99 (0.73–1.34) and 0.92 (0.49–1.75), respectively]. Similarly, no association was seen between CRP levels and risk of serrated polyps or proximal serrated polyps [quartile 4 vs. quartile 1: RR (95% CI) = 1.32 (0.85–2.03) and 1.19 (0.54–2.58), respectively]. In conclusion, this large prospective colorectal adenoma chemoprevention study found no significant relationship between CRP levels and occurrence of adenomas, advanced neoplasms, or serrated polyps. Cancer Prev Res; 7(11); 1122–7. ©2014 AACR.
Data from Biological Activity of Celecoxib in the Bronchial Epithelium of Current and Former Smokers
Authors: Kim Edward S. , Hong Waun K. , Lee J. Jack , Mao Li , Morice Rodolfo C. , Liu Diane D. , Jimenez Carlos A. , Eapen Georgie A. , Lotan Reuben , Tang Ximing , Newman Robert A. , Wistuba Ignacio I. , Kurie Jonathan M.
Published: April 2023

Abstract
Non–small cell lung cancer is the primary cause of cancer-related death in Western countries. One important approach taken to address this problem is the development of effective chemoprevention strategies. In this study, we examined whether the cyclooxygenase-2 inhibitor celecoxib, as evidenced by decreased cell proliferation, is biologically active in the bronchial epithelium of current and former smokers. Current or former smokers with at least a 20 pack-year (pack-year = number of packs of cigarettes per day times number of years smoked) smoking history were randomized into one of four treatment arms (3-month intervals of celecoxib then placebo, celecoxib then celecoxib, placebo then celecoxib, or placebo then placebo) and underwent bronchoscopies with biopsies at baseline, 3 months, and 6 months. The 204 patients were primarily (79.4%) current smokers: 81 received either low-dose celecoxib or placebo and 123 received either high-dose celecoxib or placebo. Celecoxib was originally administered orally at 200 mg twice daily and the protocol subsequently increased the dose to 400 mg twice daily. The primary end point was change in Ki-67 labeling (from baseline to 3 months) in bronchial epithelium. No cardiac toxicities were observed in the participants. Although the effect of low-dose treatment was not significant, high-dose celecoxib decreased Ki-67 labeling by 3.85% in former smokers and by 1.10% in current smokers—a significantly greater reduction (P = 0.02) than that seen with placebo after adjusting for metaplasia and smoking status. A 3- to 6-month celecoxib regimen proved safe to administer. Celecoxib (400 mg twice daily) was biologically active in the bronchial epithelium of current and former smokers; additional studies on the efficacy of celecoxib in non–small cell lung cancer chemoprevention may be warranted. Cancer Prev Res; 3(2); 148–59
Data from A Novel Combinatorial Nanotechnology-Based Oral Chemopreventive Regimen Demonstrates Significant Suppression of Pancreatic Cancer Neoplastic Lesions
Authors: Grandhi B. Karthik , Thakkar Arvind , Wang Jeffrey , Prabhu Sunil
Published: April 2023

Abstract
Pancreatic cancer is a deadly disease killing 37,000 Americans each year. Despite two decades of research on treatment options, the chances of survival are still less than 5% upon diagnosis. Recently, chemopreventive strategies have gained considerable attention as an alternative to treatment. We have previously shown significant in vitro chemopreventive effects with low-dose combinations of aspirin, curcumin, and sulforaphane (ACS) on pancreatic cancer cell lines. Here, we report the results of 24-week chemopreventive study with the oral administration of ACS combinations on the N-nitrosobis (2-oxopropyl) amine (BOP)-treated Syrian golden hamster model to suppress the progression of pancreatic intraepithelial neoplasms (PanIN) using unmodified (free drug) combinations of ACS, and nanoencapsulated (solid lipid nanoparticles; SLN) combinations of aspirin, curcumin, and free sulforaphane. The use of three different doses (low, medium, and high) of unmodified ACS combinations exhibited reduction in tumor incidence by 18%, 50%, and 68.7% respectively; whereas the modified nanoencapsulated ACS regimens reduced tumor incidence by 33%, 67%, and 75%, respectively, at 10 times lower dose compared with the free drug combinations. Similarly, although the unmodified free ACS showed a notable reduction in cell proliferation, the SLN encapsulated ACS regimens showed significant reduction in cell proliferation at 6.3%, 58.6%, and 72.8% as evidenced by proliferating cell nuclear antigen expression. Cell apoptotic indices were also upregulated by 1.5, 2.8, and 3.2 times, respectively, compared with BOP control. These studies provide a proof-of-concept for the use of an oral, low-dose, nanotechnology-based combinatorial regimen for the long-term chemoprevention of pancreatic cancer. Cancer Prev Res; 6(10); 1015–25. ©2013 AACR.
Data from Lung Cancer Risk Prediction to Select Smokers for Screening CT—a Model Based on the Italian COSMOS Trial
Authors: Maisonneuve Patrick , Bagnardi Vincenzo , Bellomi Massimo , Spaggiari Lorenzo , Pelosi Giuseppe , Rampinelli Cristiano , Bertolotti Raffaella , Rotmensz Nicole , Field John K. , DeCensi Andrea , Veronesi Giulia
Published: April 2023

Abstract
Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57–18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84–16.8), and emphysema (RR = 2.36, 95% CI = 1.59–3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models. Cancer Prev Res; 4(11); 1778–89. ©2011 AACR.
Data from Metformin Use and Lung Cancer Risk in Patients with Diabetes
Authors: Sakoda Lori C. , Ferrara Assiamira , Achacoso Ninah S. , Peng Tiffany , Ehrlich Samantha F. , Quesenberry Charles P. , Habel Laurel A.
Published: April 2023

Abstract
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages ≥40 years, who completed a health-related survey administered between 1994 and 1996, data on prescribed diabetes medications were obtained from electronic pharmacy records. Follow-up for incident lung cancer occurred from January 1, 1997, until June 30, 2012. Using Cox regression, we estimated lung cancer risk associated with new use of metformin, along with total duration, recency, and cumulative dose (all modeled as time-dependent covariates), adjusting for potential confounding factors. During 428,557 person-years of follow-up, 747 patients were diagnosed with lung cancer. No association was found with duration, dose, or recency of metformin use and overall lung cancer risk. Among never smokers, however, ever use was inversely associated with lung cancer risk [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], and risk appeared to decrease monotonically with longer use (≥5 years: HR, 0.48; 95% CI, 0.21–1.09). Among current smokers, corresponding risk estimates were >1.0, although not statistically significant. Consistent with this variation in effect by smoking history, longer use was suggestively associated with lower adenocarcinoma risk (HR, 0.69; 95% CI, 0.40–1.17), but higher small cell carcinoma risk (HR, 1.82; 95% CI, 0.85–3.91). In this population, we found no evidence that metformin use affects overall lung cancer risk. The observed variation in association by smoking history and histology requires further confirmation. Cancer Prev Res; 8(2); 174–9. ©2014 AACR.