bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Dietary Nutrient Intake, Ethnicity, and Epigenetic Silencing of Lung Cancer Genes Detected in Sputum in New Mexican Smokers
Authors: Leng Shuguang , Picchi Maria A. , Kang Huining , Wu Guodong , Filipczak Piotr T. , Juri Daniel E. , Zhang Xiequn , Gauderman W. James , Gilliland Frank D. , Belinsky Steven A.
Published: April 2023

Abstract
Lung cancer gene methylation detected in sputum assesses field cancerization and predicts lung cancer incidence. Hispanic smokers have higher lung cancer susceptibility compared with non-Hispanic whites (NHW). We aimed to identify novel dietary nutrients affecting lung cancer gene methylation and determine the degree of ethnic disparity in methylation explained by diet. Dietary intakes of 139 nutrients were assessed using a validated Harvard food frequency questionnaire in 327 Hispanics and 1,502 NHWs from the Lovelace Smokers Cohort. Promoter methylation of 12 lung cancer genes was assessed in sputum DNA. A global association was identified between dietary intake and gene methylation (Ppermutation = 0.003). Seventeen nutrient measurements were identified with magnitude of association with methylation greater than that seen for folate. A stepwise approach identified B12, manganese, sodium, and saturated fat as the minimally correlated set of nutrients whose optimal intakes could reduce the methylation by 36% (Ppermutation < 0.001). Six protective nutrients included vitamin D, B12, manganese, magnesium, niacin, and folate. Approximately 42% of ethnic disparity in methylation was explained by insufficient intake of protective nutrients in Hispanics compared with NHWs. Functional validation of protective nutrients showed an enhanced DNA repair capacity toward double-strand DNA breaks, a mechanistic biomarker strongly linked to acquisition of lung cancer gene methylation in smokers. Dietary intake is a major modifiable factor for preventing promoter methylation of lung cancer genes in smokers' lungs. Complex dietary supplements could be developed on the basis of these protective nutrients for lung cancer chemoprevention in smokers. Hispanic smokers may benefit the most from this complex for reducing their lung cancer susceptibility. Cancer Prev Res; 11(2); 93–102. ©2017 AACR.
Data from Oral Health and Risk of Upper Gastrointestinal Cancers in a Large Prospective Study from a High-risk Region: Golestan Cohort Study
Authors: Yano Yukiko , Abnet Christian C. , Poustchi Hossein , Roshandel Gholamreza , Pourshams Akram , Islami Farhad , Khoshnia Masoud , Amiriani Taghi , Norouzi Alireza , Kamangar Farin , Boffetta Paolo , Brennan Paul , Dawsey Sanford M. , Vogtmann Emily , Malekzadeh Reza , Etemadi Arash
Published: April 2023

Abstract
Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486–0.924) and gastric (HR = 0.741; 95% CI: 0.544–1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558–0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08–2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05–2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene.
Prevention Relevance:
Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers.
Data from Association of Plasma Iron Status with Subsequent Risk of Total and Site-Specific Cancer: A Large Case–Cohort Study within JPHC Study
Authors: Miyamoto Yoshihisa , Nakano Shiori , Ihira Hikaru , Yamaji Taiki , Katagiri Ryoko , Sawada Norie , Inoue Manami , Tsugane Shoichiro , Iwasaki Motoki
Published: April 2023

Abstract
It is unclear whether prediagnostic iron-related biomarkers in circulation are associated with cancer risk. We constructed a case-cohort of participants who had plasma samples available from the Japan Public Health Center—based Prospective Study and determined the incidence of cancer in these participants. We measured plasma concentrations of iron, ferritin, and hepcidin, and assessed the association between each biomarker and cancer incidence using a weighted Cox regression model. There were 4,253 participants in the sub-cohort (the randomly selected participants from an eligible, at-risk population) and 3,596 incident cancer cases (499 cases occurred in the sub-cohort). Median follow-up was for 16.5 years. In the multivariable adjusted analysis, iron deficiency (plasma ferritin <30 ng/mL) was associated with a higher risk of total cancer [adjusted HR, 1.23; 95% confidence interval (CI), 1.07–1.42] and the association was weaker after excluding those followed-up for <3 years. Iron overload was not significantly associated with total cancer (HR, 1.04; 95% CI, 0.82–1.33), but was associated with liver cancer (HR, 4.49; 95% CI, 2.71–7.43). Lower plasma levels of hepcidin and ferritin are associated with an increased gastrointestinal cancer risk. Meanwhile, lower plasma hepcidin and higher plasma ferritin levels were associated with an increased liver cancer risk. In conclusion, there was no association between iron overload and cancer risk, besides liver cancer.
Prevention relevance:
High ferritin and low hepcidin levels in the plasma were associated with increased liver cancer risk. Evaluating iron metabolism including hepcidin levels may help identify people with high liver cancer risk.
Data from Epidemiologic Risk Factors in a Comparison of a Barrett Esophagus Registry (BarrettNET) and a Case–Control Population in Germany
Authors: Schmidt Melissa , Ankerst Donna P. , Chen Yiyao , Wiethaler Maria , Slotta-Huspenina Julia , Becker Karl-Friedrich , Horstmann Julia , Kohlmayer Florian , Lehmann Andreas , Linkohr Birgit , Strauch Konstantin , Schmid Roland M. , Quante Anne S. , Quante Michael
Published: April 2023

Abstract
Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population “at risk” compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.
Data from Uptake and Predictors of Opportunistic Salpingectomy for Ovarian Cancer Risk Reduction in the United States
Authors: Karia Pritesh S. , Joshu Corinne E. , Visvanathan Kala
Published: April 2023

Abstract
Evidence suggesting that high-grade serous ovarian cancers originate in the fallopian tubes has led to the emergence of opportunistic salpingectomy (OS) as an approach to reduce ovarian-cancer risk. In the U.S., some national societies now recommend OS in place of tubal ligation for sterilization or during a benign hysterectomy in average-risk women. However, limited data exist on the dissemination of OS in clinical practice. We examined the uptake and predictors of OS in a nationwide sample of inpatient and outpatient claims (N = 48,231,235) from 2010 to 2017. Incidence rates of OS were calculated, and an interrupted time-series analysis was used to quantify changes in rates before (2010–2013) and after (2015–2017) national guideline release. Predictors of OS use were examined using Poisson regression. From 2010 to 2017, the age-adjusted incidence rate of OS for sterilization and OS during hysterectomy increased 17.8-fold [95% confidence interval (CI), 16.2–19.5] and 7.6-fold (95% CI, 5.5–10.4), respectively. The rapid increase (age-adjusted increase in quarterly rates of between 109% and 250%) coincided with the time of national guideline release. In multivariable-adjusted analyses, OS use was more common in young women and varied significantly by geographic region, rurality, family history/genetic susceptibility, surgical indication, inpatient/outpatient setting, and underlying comorbidities. Similar differences in OS uptake were noted in analyses limited to women with a family history/genetic susceptibility to breast/ovarian cancer. Our results highlight significant differences in OS uptake in both high- and average-risk women. Defining subsets of women who would benefit most from OS and identifying barriers to equitable OS uptake is needed.
Prevention Relevance:
Opportunistic salpingectomy for ovarian-cancer risk reduction has been rapidly adopted in the U.S., with significant variation in uptake by demographic and clinical factors. Studies examining barriers to opportunistic salpingectomy access and the long-term effectiveness and potential adverse effects of opportunistic salpingectomy are needed.
Data from Specificity of the Multi-Target Stool DNA Test for Colorectal Cancer Screening in Average-Risk 45–49 Year-Olds: A Cross-Sectional Study
Authors: Imperiale Thomas F. , Kisiel John B. , Itzkowitz Steven H. , Scheu Bradley , Duimstra Emma Kate , Statz Sandra , Berger Barry M. , Limburg Paul J.
Published: April 2023

Abstract
High-specificity colorectal cancer screening is desirable to triage patients <50 years for colonoscopy; however, most endorsed colorectal cancer screening tests have not been rigorously evaluated in younger populations. This prospective cross-sectional study determined the specificity of the multitarget stool DNA (mt-sDNA) test in an average-risk screening population of 45 to 49 year-olds. Specificity was the primary outcome and was measured in participants without colorectal cancer or advanced precancerous lesions [APL– advanced adenomas (AA), and sessile serrated lesions ≥10 mm], and in the subgroup of participants with negative colonoscopic findings. APL sensitivity was a secondary outcome. The evaluable cohort included those who completed the study without protocol deviations and had a usable mt-sDNA test. Of 983 enrolled participants, 816 formed the evaluable cohort, with a mean age of 47.8 (SD, 1.5) years; 47.7% were women. No participants had colorectal cancer, 49 had APL, 253 had nonadvanced adenomas (NAA), and 514 had negative colonoscopic findings. mt-sDNA test specificity was 95.2% (95% CI, 93.4–96.6) in participants with NAA or negative findings [96.3% (confidence interval (CI), 94.3%–97.8%)] in those with negative findings, and did not differ by sex (P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9–47.5%), with most APL (83.7%) measuring 10–19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64–0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening.
Prevention Relevance:
This study shows that mt-sDNA has high specificity among average-risk 45–49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.
Data from Oral Cancer Risk Assessment for Different Types of Smokeless Tobacco Products Sold Worldwide: A Review of Reviews and Meta-analyses
Authors: Gupta Alpana K. , Kanaan Mona , Siddiqi Kamran , Sinha Dhirendra N. , Mehrotra Ravi
Published: April 2023

Abstract
Smokeless tobacco (SLT) use is a significant cause of lip and oral cavity cancers. Globally, oral cancer prevalence is strongly linked to the types of tobacco products used, their chemical composition, and their pattern of use. Except snus, all SLT products sold in different World Health Organization regions are strongly associated with oral cancer incidence. Shammah showed the highest association OR with 95% confidence intervals (CI; OR, 38.74; 95% CI, 19.50–76.96), followed by oral snuff (OR, 11.80; 95% CI, 8.45–16.49), gutkha (OR, 8.67; 95% CI, 3.59–20.93), tobacco with betel quid (OR, 7.74; 95% CI, 5.38–11.13), toombak (OR, 4.72; 95% CI, 2.88–7.73), and unspecified chewing tobacco (OR, 4.72; 95% CI, 3.13–7.11). Most SLT products containing high levels of carcinogenic tobacco-specific nitrosamines (TSNA) exhibit a high risk of oral cancer. There is an urgent need to frame and implement international policies for oral cancer prevention through legal control of the TSNA levels in all SLT product types.
Prevention Relevance:
Most smokeless tobacco products sold worldwide, mainly shammah, toombak, gutkha, betel quid with tobacco, and dry snuff, are associated with a high risk of oral cancer. A high concentration of tobacco-specific nitrosamines in smokeless tobacco products is the major causative factor for oral cancer development.
Data from Stakeholder Perspectives on Overcoming Barriers to Cascade Testing in Lynch Syndrome: A Qualitative Study
Authors: Srinivasan Swetha , Hampel Heather , Leeman Jennifer , Patel Amit , Kulchak Rahm Alanna , Reuland Daniel S. , Roberts Megan C.
Published: April 2023

Abstract
Cascade testing (i.e., genetic testing of family members of individuals with disease) among families affected by hereditary cancer disorders, such as Lynch syndrome, is suboptimal and thus represents a missed opportunity in cancer prevention. We aimed to fill a gap in the literature by exploring multilevel barriers and facilitators to the implementation of cascade testing for Lynch syndrome. We conducted semistructured, in-depth interviews guided by the Consolidated Framework for Implementation Research and the Integrated Behavioral Model among key stakeholders (n = 60): Patients with Lynch syndrome and relatives (n = 20), providers (n = 20), and administrators (n = 20). Transcripts were double-coded (20% sample) using template analysis in ATLAS.ti. Barriers identified included (i) low awareness about Lynch syndrome, (ii) psychosocial barriers, (iii) lack of provider follow-up, (iv) accessibility to genetic counseling, and (v) fear of discrimination. Facilitators included (i) motivation to engage in cascade testing and (ii) free genetic testing offered to relatives. Stakeholders also recommended strategies to overcome implementation barriers in the short-term (increasing education, preparing patients for communicating with relatives), medium-term (optimizing clinical workflow and staffing resources), and long-term (nationwide standardization). These findings indicate that modifiable, multilevel barriers to the implementation of cascade testing in Lynch syndrome are experienced across stakeholders. Understanding and targeting implementation barriers is imperative to achieving public health impact of precision health interventions such as cascade testing.
Data from Height and Body Size in Childhood, Adolescence, and Young Adulthood and Breast Cancer Risk According to Molecular Subtype in the Nurses' Health Studies
Authors: Warner Erica T. , Hu Rong , Collins Laura C. , Beck Andrew H. , Schnitt Stuart , Rosner Bernard , Eliassen A. Heather , Michels Karin B. , Willett Walter C. , Tamimi Rulla M.
Published: April 2023

Abstract
Height and body size in childhood and young adulthood have been consistently associated with breast cancer risk; whether associations differ across molecular subtypes is unclear. In a pooled analysis of the Nurses' Health Studies, we prospectively examined the association of four exposures: height, body mass index (BMI) at the age of 18 years, childhood and adolescent somatotypes, with breast cancer risk according to molecular subtypes defined by immunohistochemical markers. We used multivariable-adjusted Cox proportional hazards regression to estimate HRs and 95% confidence intervals (CI). We identified 2,983 luminal A, 1,281 luminal B, 318 HER2-enriched, 408 basal-like, and 128 unclassified tumors. Height was positively associated with all subtypes (Pheterogeneity = 0.78). BMI at the age of 18 (Pheterogeneity = 0.001), childhood (Pheterogeneity = 0.51), and adolescent somatotype (Pheterogeneity = 0.046) were inversely associated, but with differences in magnitude of association. BMI at the age of 18 of ≥25 kg/m2 (compared with 20–21.9 kg/m2) was associated with a 52% decreased risk of HER2-enriched (HR, 0.48; 95% CI, 0.26–0.91; Ptrend < 0.0001) and 39% reduced risk of basal-like tumors (HR, 0.61; 95% CI, 0.36–1.02; Ptrend = 0.008). Compared with the lowest category, women in the highest adolescent body size category were 71% less likely to develop HER2-enriched (HR, 0.29; 95% CI, 0.10–0.85; Ptrend = 0.0005) and 60% less likely to develop basal-like (HR, 0.40; 95% CI, 0.17–0.95; Ptrend = 0.0008). Height was positively associated with risk of all breast cancer molecular subtypes. BMI at 18 years and childhood and adolescent were inversely associated with risk of most breast cancer molecular subtypes with somewhat stronger associations with HER2-enriched and basal-like subtypes. Cancer Prev Res; 9(9); 732–8. ©2016 AACR.
Data from Combination of Erlotinib and Naproxen Employing Pulsatile or Intermittent Dosing Profoundly Inhibits Urinary Bladder Cancers
Authors: Mohammed Altaf , Miller Mark Steven , Lubet Ronald A. , Suen Chen S. , Sei Shizuko , Shoemaker Robert H. , Juliana Margaret M. , Moeinpour Fariba L. , Grubbs Clinton J.
Published: April 2023

Abstract
Daily dosing of either NSAIDs or EGFR inhibitors has been shown to prevent bladder cancer development in a N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced rat model. However, these inhibitors cause gastrointestinal ulceration and acneiform rash, respectively, limiting their continuous use in a clinical prevention setting. We studied chemopreventive efficacy of pulsatile dosing of EGFR inhibitor erlotinib (42 mg/kg BW, once/week) combined with intermittent or continuous low doses of the NSAID naproxen (30 mg/kg BW/day, 3 weeks on/off or 128 ppm daily in diet) in the OH-BBN induced rat bladder cancer model. The interventions were started either at 1 or 4 weeks (early intervention) or 3 months (delayed intervention) after the last OH-BBN treatment, by which time the rats had developed microscopic bladder lesions. All combination regimens tested as early versus late intervention led to the reduction of the average bladder tumor weights (54%–82%; P < 0.01 to P < 0.0001), a decrease in tumor multiplicity (65%–85%; P < 0.01 to P < 0.0001), and a decrease in the number of rats with large palpable tumors (>200 mg; 83%–90%; P < 0.01 to P < 0.0001). Levels of signal transduction markers, Ki-67, cyclin D1, IL1β, pSTAT3, and pERK, were significantly (P < 0.05 to P < 0.001) reduced in the treated tumors, demonstrating their potential utility as predictive markers for efficacy. These findings demonstrate that significant chemopreventive efficacy could be achieved with alternative intervention regimens designed to reduce the toxicity of agents, and that starting erlotinib and/or naproxen treatments at the time microscopic tumors were present still conferred the efficacy.
Data from Comprehensive Analysis of Multiple Cohort Datasets Deciphers the Utility of Germline Single-Nucleotide Polymorphisms in Prostate Cancer Diagnosis
Authors: Zhang Wensheng , Dong Yan , Sartor Oliver , Zhang Kun
Published: April 2023

Abstract
Prostate cancer susceptibility is a polygenic trait. We aimed to examine the controversial diagnostic utility of single-nucleotide polymorphisms (SNP) for prostate cancer. We analyzed two datasets collected from Europeans and one from Africans. These datasets were generated by the genome-wide association studies, that is, CGEMS, BPC3, and MEC-Africans, respectively. About 540,000 SNPs, including 61 risk markers that constitute a panel termed MK-61, were commonly genotyped. For each dataset, we augmented the MK-61 panel to generate an MK-61+ one by adding several thousands of SNPs that were moderately associated with prostate cancer occurrence in external dataset(s). We assessed the diagnostic utility of both panels by measuring their predictive strength for prostate cancer occurrence with AUC statistics. We calculated the theoretical AUCs using quantitative genetics model-based formulae and obtained the empirical estimates via 10-fold cross-validation using statistical and machine learning techniques. For the MK-61 panel, the 95% confidence intervals of the theoretical AUCs (AUC-CI.95) were 0.578–0.655, 0.596–0.656, and 0.539–0.596 in the CGEMS, BPC3, and MEC-Africans cohorts, respectively. For the MK-61+ panels, the corresponding AUC-CI.95 were 0.617–0.663, 0.527–0.736, and 0.547–0.565. The empirical AUCs largely fell within the theoretical interval. A promising result (AUC = 0.703, FNR = 0.354, FPR = 0.353) was obtained in the BPC3 cohort when the MK-61+ panel was used. In the CGEMS cohort, the MK-61+ panel complemented PSA in predicting the disease status of PSA ≥ 2.0 ng/mL samples. This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with {\rm{PSA}} \ge 2.0\ $ng/mL.
Prevention Relevance:
This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with PSA ≥ 2 ng/mL.
Data from Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis
Authors: Huang Kevin M. , Liang Sherry , Yeung Steven , Oiyemhonlan Etuajie , Cleveland Kristan H. , Parsa Cyrus , Orlando Robert , Meyskens Frank L. , Andresen Bradley T. , Huang Ying
Published: April 2023

Abstract
In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P+ cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol on UV-induced neoplastic transformation. Both carvedilol and 4-OHC (1 μmol/L) blocked transformation induced by chronic UV (15 mJ/cm2) exposure for 8 weeks. However, EGF-mediated transformation was inhibited by only carvedilol but not by 4-OHC. Carvedilol (1 and 5 μmol/L), but not 4-OHC, attenuated UV-induced AP-1 and NF-κB luciferase reporter activity, suggesting a potential anti-inflammatory activity. In a single-dose UV (200 mJ/cm2)-induced skin inflammation mouse model, carvedilol (10 μmol/L), applied topically after UV exposure, reduced skin hyperplasia and the levels of cyclobutane pyrimidine dimers, IL1β, IL6, and COX-2 in skin. In SKH-1 mice exposed to gradually increasing levels of UV (50–150 mJ/cm2) three times a week for 25 weeks, topical administration of carvedilol (10 μmol/L) after UV exposure increased tumor latency compared with control (week 18 vs. 15), decreased incidence and multiplicity of squamous cell carcinomas, while 4-OHC had no effect. These data suggest that carvedilol has a novel chemopreventive activity and topical carvedilol following UV exposure may be repurposed for preventing skin inflammation and cancer. Cancer Prev Res; 10(10); 598–606. ©2017 AACR.
Data from Retention and Evaluation of Precision and Generic Prevention Materials for Melanoma: A Qualitative Study Comparing Young Adults and Adults
Authors: Crowder Sylvia L. , Buro Acadia W. , Lacson John Charles A. , Kim Youngchul , Sutton Steven K. , Roetzheim Richard G. , Vadaparampil Susan T. , Stern Marilyn , Kanetsky Peter A.
Published: April 2023

Abstract
A randomized trial was conducted to examine whether providing precision prevention materials incorporating melanocortin-1 receptor genetic risk information would increase intention to practice melanoma preventive behaviors. Here, we determine retention/evaluation of prevention materials for adolescent and young adults (AYA) 18 to 39 years old versus adults aged 40+ at 6 and 12 months as an a priori adjunct analysis to the primary research question. Using qualitative methodology, open-ended questions probing most important information from prevention materials and additional comments were collected at 6 and 12 months after baseline. Descriptive statistics were performed on demographic/self-reported characteristics. Two independent researchers applied qualitative thematic content analysis to identify major themes in open-ended questions. Of the 1,134 participants randomized, 906 completed at least one of the follow-up surveys and contributed to analyses of intervention efficacy. Five major thematic categories emerged from the open-ended response data: (i) tips and tricks for sun protection; (ii) cancer prevention; (iii) risk factors and genetics; (iv) general information; and (v) intervention comments. Across all ages, the most important information retained were sun protection techniques in the generic prevention materials group and identifying the importance of genetic risk factors/implementing lifestyle behavior changes in the precision prevention materials group. For additional comments, AYA participants in the generic prevention materials group preferred more scientific information including statistics and citations for references while adults were more likely to state they already knew cancer prevention techniques. Results provide unique qualitative evaluation of AYA versus adult retention of prevention materials for melanoma that enhance quantitative findings.
Prevention Relevance:
It is important to evaluate information within groups defined by periods of the life trajectory, e.g., AYA and adults, to best inform preferences, knowledge, and motivation for behavior change. By assessing retention, evidence-based interventions can be designed to better support public health messaging and encourage positive health behaviors.
Data from Risk of Skin Cancer Associated with Metformin Use: A Meta-Analysis of Randomized Controlled Trials and Observational Studies
Authors: Chang Michael S. , Hartman Rebecca I. , Xue Junchao , Giovannucci Edward L. , Nan Hongmei , Yang Keming
Published: April 2023

Abstract
Previous studies demonstrate mixed evidence regarding the association between metformin and skin cancer risk. To synthesize prior evidence and evaluate the association between metformin and skin cancer risk in patients with diabetes/prediabetes, we conducted a meta-analysis. A systematic literature search was performed up to March 23, 2020 to identify randomized controlled trials (RCT) and observational studies of metformin that reported any event of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. In a meta-analysis of 6 trials involving 8,541 patients (Peto method), compared with controls, metformin was not significantly associated with decreased risk of melanoma [OR, 0.82; 95% confidence interval (CI), 0.27–2.43], BCC (OR, 0.75; 95% CI, 0.36–1.57), SCC (OR, 0.98; 95% CI, 0.06–15.60), total nonmelanoma skin cancer (NMSC; OR, 0.69; 95% CI, 0.38–1.24), or total skin cancer (OR, 0.71; 95% CI, 0.42–1.20). This nonsignificant association pattern was consistent with the random-effects meta-analysis of 4 cohort studies with 354,746 patients (melanoma: RR, 0.91; 95% CI, 0.62–1.33; NMSC: RR, 0.65; 95% CI, 0.35–1.18; total skin cancer: RR, 0.83; 95% CI, 0.59–1.16). In conclusion, meta-analyses of both RCT and cohort studies showed no statistically significant association between metformin and skin cancer risks, although suggestive evidence of modestly reduced risks of skin cancer among metformin users was observed. Further studies are needed.
Prevention Relevance:
Meta-analyses of RCT and cohort studies showed no significant association between metformin and skin cancer, although suggestive evidence of modestly reduced skin cancer risks among metformin users was observed. These findings suggest metformin use should not influence current medical decision making for diabetes patients at risk of developing skin cancer.
Data from Sociocultural Factors, Access to Healthcare, and Lifestyle: Multifactorial Indicators in Association with Colorectal Cancer Risk
Authors: Warren Andersen Shaneda , Zheng Wei , Steinwandel Mark , Murff Harvey J. , Lipworth Loren , Blot William J.
Published: April 2023

Abstract
Black Americans of low socioeconomic status (SES) have higher colorectal cancer incidence than other groups in the United States. However, much of the research that identifies colorectal cancer risk factors is conducted in cohorts of high SES and non-Hispanic White participants. Adult participants of the Southern Community Cohort Study (N = 75,182) were followed for a median of 12.25 years where 742 incident colorectal cancers were identified. The majority of the cohort are non-Hispanic White or Black and have low household income. Cox models were used to estimate HRs for colorectal cancer incidence associated with sociocultural factors, access to and use of healthcare, and healthy lifestyle scores to represent healthy eating, alcohol intake, smoking, and physical activity. The association between Black race and colorectal cancer was consistent and not diminished by accounting for SES, access to healthcare, or healthy lifestyle [HR = 1.34; 95% confidence interval (CI),1.10–1.63]. Colorectal cancer screening was a strong, risk reduction factor for colorectal cancer (HR = 0.65; 95% CI, 0.55–0.78), and among colorectal cancer-screened, Black race was not associated with risk. Participants with high school education were at lower colorectal cancer risk (HR = 0.81; 95% CI, 0.67–0.98). Income and neighborhood-level SES were not strongly associated with colorectal cancer risk. Whereas individual health behaviors were not associated with risk, participants that reported adhering to ≥3 health behaviors had a 19% (95% CI, 1–34) decreased colorectal cancer risk compared with participants that reported ≤1 behaviors. The association was consistent in fully-adjusted models, although HRs were no longer significant. Colorectal cancer screening, education, and a lifestyle that includes healthy behaviors lowers colorectal cancer risk. Racial disparities in colorectal cancer risk may be diminished by colorectal cancer screening.
Prevention Relevance:
Colorectal cancer risk may be reduced through screening, higher educational attainment and performing more health behaviors. Importantly, our data show that colorectal cancer screening is an important colorectal cancer prevention strategy to eliminate the racial disparity in colorectal cancer risk.

See related Spotlight, p. 561
Data from Common Analgesic Use for Menstrual Pain and Ovarian Cancer Risk
Authors: Sasamoto Naoko , Babic Ana , Vitonis Allison F. , Titus Linda , Cramer Daniel W. , Trabert Britton , Tworoger Shelley S. , Terry Kathryn L.
Published: April 2023

Abstract
Menstrual pain has been associated with increased ovarian cancer risk, presumably through increased inflammation, which is known to play a critical role in ovarian carcinogenesis. Analgesic medications are frequently used to treat menstrual pain, some of which lower ovarian cancer risk. In this study, we examined the association between analgesic use for menstrual pain during the premenopausal period and ovarian cancer risk among women with history of menstrual pain. We used data from the New England Case-Control Study, including 1,187 epithelial ovarian cancer cases and 1,225 population-based controls enrolled between 1998 and 2008 with detailed information on analgesic use for their menstrual pain. We used unconditional logistic regression to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between analgesic use (i.e., aspirin, ibuprofen, acetaminophen) for menstrual pain and ovarian cancer risk. We further conducted a stratified analysis by intensity of menstrual pain (mild/moderate, severe). Among women with menstrual pain during their 20s and 30s, ever use of analgesics for menstrual pain was not significantly associated with ovarian cancer risk. However, among women with severe menstrual pain, ever use of aspirin or acetaminophen for menstrual pain was inversely associated with risk (OR, 0.41; 95% CI, 0.18–0.94 and OR, 0.43; 95% CI, 0.21–0.88 compared with never users, respectively). No significant association was observed between analgesic use and ovarian cancer risk among women with mild/moderate menstrual pain (Pinteraction ≤ 0.03). Our results suggest that use of aspirin or acetaminophen for severe menstrual pain may be associated with lower risk of ovarian cancer.
Prevention Relevance:
This study investigates whether analgesic use specifically for menstrual pain during the premenopausal period influences ovarian cancer risk. Our results suggest use of aspirin or acetaminophen for severe menstrual pain may be associated with lower risk of ovarian cancer among women with severe menstrual pain.
Data from High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer
Authors: Bannon Sarah A. , Montiel Maria F. , Goldstein Jennifer B. , Dong Wenli , Mork Maureen E. , Borras Ester , Hasanov Merve , Varadhachary Gauri R. , Maitra Anirban , Katz Matthew H. , Feng Lei , Futreal Andrew , Fogelman David R. , Vilar Eduardo , McAllister Florencia
Published: April 2023

Abstract
Introduction: We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis.

Methods: Patients from two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations were determined, and clinical characteristics including survival were analyzed.

Results: A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC [odds ratios (OR), 1.93 ± 1.03–3.70, P = 0.039] and GC (4.78 ± 1.10–32.95, P = 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR, 0.44; 95% CI of HR, 0.25–0.76, P = 0.030).

Discussion: Germline mutations are highly prevalent in patients with PDAC of early onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset. Cancer Prev Res; 11(11); 679–86. ©2018 AACR.
Data from Randomized Double-Blind Placebo-Controlled Biomarker Modulation Study of Vitamin D Supplementation in Premenopausal Women at High Risk for Breast Cancer (SWOG S0812)
Authors: Crew Katherine D. , Anderson Garnet L. , Hershman Dawn L. , Terry Mary Beth , Tehranifar Parisa , Lew Danika L. , Yee Monica , Brown Eric A. , Kairouz Sebastien S. , Kuwajerwala Nafisa , Bevers Therese , Doster John E. , Zarwan Corrine , Kruper Laura , Minasian Lori M. , Ford Leslie , Arun Banu , Neuhouser Marian , Goodman Gary E. , Brown Powel H.
Published: April 2023

Abstract
Observational studies have reported an inverse association between vitamin D intake and breast cancer risk. We examined whether vitamin D supplementation in high-risk premenopausal women reduces mammographic density (MD), an established breast cancer risk factor. We conducted a multicenter randomized double-blind placebo-controlled trial in premenopausal women at high risk for breast cancer [5-year risk ≥ 1.67%, lifetime risk ≥ 20%, lobular carcinoma in situ, prior stage 0–II breast cancer, hereditary breast cancer syndrome, or high MD (heterogeneously/extremely dense)], with a baseline serum 25-hydroxyvitamin D [25(OH)D] ≤ 32 ng/mL. Participants were randomized to 12 months of vitamin D3 20,000 IU/week or matching placebo. The primary endpoint was change in MD from baseline to 12 months using the Cumulus technique. Secondary endpoints included serial blood biomarkers [25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), insulin-like growth factor (IGF)-1, IGF-binding protein-3] and MD change at 24 months. Among 208 women randomized, median age was 44.6 years, 84% were white, 33% had baseline 25(OH)D < 20 ng/mL, and 78% had high baseline MD. Comparing the active and placebo groups at 12 months, MD changes were small and did not significantly differ. Mean MD changes at 12 and 24 months were −0.3% and −1.2%, respectively, in the active arm and +1.5% and +1.6% with placebo (P > 0.05). We observed a mean change in serum 25(OH)D of +18.9 versus +2.8 ng/mL (P < 0.01) and IGF-1 of −9.8 versus −1.8 ng/mL (P = 0.28), respectively. At 12 months, MD was positively correlated with serum IGF-1 and IGF-1/IGFBP-3 (P < 0.01). This trial does not support the use of vitamin D supplementation for breast cancer risk reduction.
Data from Spatial Variation of the Native Colon Microbiota in Healthy Adults
Authors: Flynn Kaitlin J. , Ruffin Mack T. , Turgeon D. Kim , Schloss Patrick D.
Published: April 2023

Abstract
The microbiome has been implicated in the development of colorectal cancer and inflammatory bowel diseases. The specific traits of these diseases vary along the axis of the digestive tract. Further, variation in the structure of the gut microbiota has been associated with both diseases. We profiled the microbiota of the healthy proximal and distal mucosa and lumen to better understand how bacterial populations vary along the colon. We used a two-colonoscope approach to sample proximal and distal mucosal and luminal contents from the colons of 20 healthy subjects that had not undergone any bowel preparation procedure. The biopsies and home-collected stool were subjected to 16S rRNA gene sequencing, and random forest classification models were built using taxa abundance and location to identify microbiota specific to each site. The right mucosa and lumen had the most similar community structures of the five sites we considered from each subject. The distal mucosa had higher relative abundance of Finegoldia, Murdochiella, Peptoniphilus, Porphyromonas, and Anaerococcus. The proximal mucosa had more of the genera Enterobacteriaceae, Bacteroides, and Pseudomonas. The classification model performed well when classifying mucosal samples into proximal or distal sides (AUC = 0.808). Separating proximal and distal luminal samples proved more challenging (AUC = 0.599), and specific microbiota that differentiated the two were hard to identify. By sampling the unprepped colon, we identified distinct bacterial populations native to the proximal and distal sides. Further investigation of these bacteria may elucidate if and how these groups contribute to different disease processes on their respective sides of the colon. Cancer Prev Res; 11(7); 393–402. ©2018 AACR.
Data from Primary Care Provider Beliefs and Recommendations About Colorectal Cancer Screening in Four Healthcare Systems
Authors: Ghai Nirupa R. , Jensen Christopher D. , Merchant Sophie A. , Schottinger Joanne E. , Lee Jeffrey K. , Chubak Jessica , Kamineni Aruna , Halm Ethan A. , Skinner Celette Sugg , Haas Jennifer S. , Green Beverly B. , Cannizzaro Nancy T. , Schneider Jennifer L. , Corley Douglas A.
Published: April 2023

Abstract
Primary care provider's (PCP) perceptions of colorectal cancer screening test effectiveness and their recommendations for testing intervals influence patient screening uptake. Few large studies have examined providers’ perceptions and recommendations, including their alignment with evidence suggesting comparable test effectiveness and guideline recommendations for screening frequency. Providers (n = 1,281) within four healthcare systems completed a survey in 2017–2018 regarding their perceptions of test effectiveness and recommended intervals for colonoscopy and fecal immunochemical testing (FIT) for patients ages 40–49, 50–74, and ≥75 years. For patients 50–74 (screening eligible), 82.9% of providers rated colonoscopy as very effective versus 59.6% for FIT, and 26.3% rated colonoscopy as more effective than FIT. Also, for this age group, 77.9% recommended colonoscopy every 10 years and 92.4% recommended FIT annually. For patients ages 40–49 and ≥75, more than one-third of providers believed the tests were somewhat or very effective, although >80% did not routinely recommend screening by either test for these age groups. Provider screening test interval recommendations generally aligned with colorectal cancer guidelines; however, 25% of providers believed colonoscopy was more effective than FIT for mortality reduction, which differs from some modeling studies that suggest comparable effectiveness. The latter finding may have implications for health systems where FIT is the dominant screening strategy. Only one-third of providers reported believing these screening tests were effective in younger and older patients (i.e., <50 and ≥75 years). Evidence addressing these beliefs may be relevant if cancer screening recommendations are modified to include older and/or younger patients.
Data from Weight is More Informative than Body Mass Index for Predicting Postmenopausal Breast Cancer Risk: Prospective Family Study Cohort (ProF-SC)
Authors: Ye Zhoufeng , Li Shuai , Dite Gillian S. , Nguyen Tuong L. , MacInnis Robert J. , Andrulis Irene L. , Buys Saundra S. , Daly Mary B. , John Esther M. , Kurian Allison W. , Genkinger Jeanine M. , Chung Wendy K. , Phillips Kelly-Anne , Thorne Heather , Winship Ingrid M. , Milne Roger L. , Dugué Pierre-Antoine , Southey Melissa C. , Giles Graham G. , Terry Mary Beth , Hopper John L.
Published: April 2023

Abstract
We considered whether weight is more informative than body mass index (BMI) = weight/height2 when predicting breast cancer risk for postmenopausal women, and if the weight association differs by underlying familial risk. We studied 6,761 women postmenopausal at baseline with a wide range of familial risk from 2,364 families in the Prospective Family Study Cohort. Participants were followed for on average 11.45 years and there were 416 incident breast cancers. We used Cox regression to estimate risk associations with log-transformed weight and BMI after adjusting for underlying familial risk. We compared model fits using the Akaike information criterion (AIC) and nested models using the likelihood ratio test. The AIC for the weight-only model was 6.22 units lower than for the BMI-only model, and the log risk gradient was 23% greater. Adding BMI or height to weight did not improve fit (ΔAIC = 0.90 and 0.83, respectively; both P = 0.3). Conversely, adding weight to BMI or height gave better fits (ΔAIC = 5.32 and 11.64; P = 0.007 and 0.0002, respectively). Adding height improved only the BMI model (ΔAIC = 5.47; P = 0.006). There was no evidence that the BMI or weight associations differed by underlying familial risk (P > 0.2). Weight is more informative than BMI for predicting breast cancer risk, consistent with nonadipose as well as adipose tissue being etiologically relevant. The independent but multiplicative associations of weight and familial risk suggest that, in terms of absolute breast cancer risk, the association with weight is more important the greater a woman's underlying familial risk.
Prevention Relevance:
Our results suggest that the relationship between BMI and breast cancer could be due to a relationship between weight and breast cancer, downgraded by inappropriately adjusting for height; potential importance of anthropometric measures other than total body fat; breast cancer risk associations with BMI and weight are across a continuum.
Data from Complementary Longitudinal Serum Biomarkers to CA125 for Early Detection of Ovarian Cancer
Authors: Simmons Archana R. , Fourkala Evangelia Ourania , Gentry-Maharaj Aleksandra , Ryan Andy , Sutton Margie N. , Baggerly Keith , Zheng Hui , Lu Karen H. , Jacobs Ian , Skates Steven , Menon Usha , Bast Robert C.
Published: April 2023

Abstract
Early detection of ovarian cancer has the potential to impact mortality. A multimodal screening strategy where rising CA125 values over time, analyzed with the risk of ovarian cancer algorithm (ROCA), triggers transvaginal sonography and possible surgery has high sensitivity and specificity, but still fails to detect the 20% of early-stage cases that do not express CA125. Use of multiple biomarkers could detect cases missed by CA125. We have studied the sensitivity and lead time of a multi-marker panel (CA125, HE4, MMP-7, and CA 72-4) compared with CA125 alone. We used PRoBE design principles to select preclinical longitudinal specimens from 75 women (50 screen-positive, 25 screen-negative) who developed invasive epithelial ovarian cancer (3–5 serial specimens each) and 547 corresponding healthy controls (1–10 serial specimens each) from the ovarian cancer screening trial, UKCTOCS, in a blinded fashion. We measured the multi-marker concentrations in ultra-low serum volumes (16 μL) utilizing multiplexed bead-based immunoassays with low detection limits, high inter- and intra-assay precision, negligible cross-reactivity, and good correlation with standard immunoassays. While, at least one of the complementary biomarkers rose with CA125 in 44% (22/50) of screen-positive cases, there was no advantage in lead time over CA125. Therefore, we developed single-marker longitudinal algorithms (ROCA-like) to determine the presence of a change point to distinguish between the cases and controls. Using these algorithms, at 98% specificity, HE4 and CA72-4 identified 16% (4/25) of screen-negative cases, while MMP-7 identified none. Taken together, HE4 and CA72-4 show promise as complementary biomarkers to CA125 for longitudinal screening.