bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Specialty Supplement Use and Biologic Measures of Oxidative Stress and DNA Damage
Authors: Kantor Elizabeth D. , Ulrich Cornelia M. , Owen Robert W. , Schmezer Peter , Neuhouser Marian L. , Lampe Johanna W. , Peters Ulrike , Shen Danny D. , Vaughan Thomas L. , White Emily
Published: April 2023

Abstract
Background: Oxidative stress and resulting cellular damage have been suggested to play a role in the etiology of several chronic diseases, including cancer and cardiovascular disease. Identifying factors associated with reduced oxidative stress and resulting damage may guide future disease-prevention strategies.

Methods: In the VITamins And Lifestyle (VITAL) biomarker study of 209 persons living in the Seattle area, we examined the association between current use of several specialty supplements and oxidative stress, DNA damage, and DNA repair capacity. Use of glucosamine, chondroitin, fish oil, methylsulfonylmethane (MSM), coenzyme Q10 (CoQ10), ginseng, ginkgo, and saw palmetto was ascertained by a supplement inventory/interview, whereas the use of fiber supplements was ascertained by questionnaire. Supplements used by more than 30 persons (glucosamine and chondroitin) were evaluated as the trend across number of pills/week (non-use, <14 pills/week, 14+ pills/week), whereas less commonly used supplements were evaluated as use/non-use. Oxidative stress was measured by urinary 8-isoprostane and PGF2α concentrations using enzyme immunoassays (EIA), whereas lymphocyte DNA damage and DNA repair capacity were measured using the Comet assay. Multivariate-adjusted linear regression was used to model the associations between supplement use and oxidative stress/DNA damage.

Results: Use of glucosamine (Ptrend: 0.01), chondroitin (Ptrend: 0.003), and fiber supplements (P: 0.01) was associated with reduced PGF2α concentrations, whereas CoQ10 supplementation was associated with reduced baseline DNA damage (P: 0.003).

Conclusions: Use of certain specialty supplements may be associated with reduced oxidative stress and DNA damage.

Impact: Further research is needed to evaluate the association between specialty supplement use and markers of oxidative stress and DNA damage. Cancer Epidemiol Biomarkers Prev; 22(12); 2312–22. ©2013 AACR.
Data from Limited PSA Testing in Indigent Men in South Texas: An Appropriate Care or Missing a Prevention Opportunity?
Authors: Liang Yuanyuan , Du Fei , Thompson Ian M. , Turner Barbara J.
Published: April 2023

Abstract
Background: No previous study has examined racial ethnic differences in prostate-specific antigen (PSA) testing and followup in primary care practices serving an indigent population.

Methods: From electronic medical records of primary care practices affiliated with one health care system in San Antonio, we identified 9,267 men aged 50 to 74 with 2+ clinic visits from 2008 through 2010 and no prior prostate cancer diagnosis. Logistic regression was used to examine the association of race ethnicity with the use of PSA testing and, if tested, with an abnormal result (≥4 ng/mL) adjusted for demographics, health care, and clinical factors. Time to a follow-up activity after an abnormal PSA was assessed using Cox proportional models.

Results: The race ethnicity of this cohort was 63% Hispanic, 27% non-Hispanic white, 7% African-American, and 3% other. In a 3-year period, 26.8% of men had at least one PSA test. Compared with African-Americans, non-Hispanic whites were less likely to be tested [OR, 0.68; 95% confidence interval (CI), 0.55–0.83] but Hispanics did not differ (OR = 0.95; 95% CI 0.79–1.15). African-Americans were more likely to have an abnormal PSA than others (12.4% vs. 5.2%, P < 0.001) and the shortest adjusted time to follow-up (P = 0.004).

Conclusions: In this 3-year indigent cohort, about one quarter had a PSA test, approximately half of the national testing rate.

Impact: African-Americans were more likely to be tested than non-Hispanic whites but had more abnormal results, raising concerns about missed prevention opportunities. African-Americans with high PSA results had the shortest time until follow-up, reflecting awareness of the threat of prostate cancer for African-Americans by physicians. Cancer Epidemiol Biomarkers Prev; 21(9); 1489–96. ©2012 AACR.
Data from Cancer-Directed Therapy and Hospice Care for Metastatic Cancer in American Indians and Alaska Natives
Authors: Shiovitz Stacey , Bansal Aasthaa , Burnett-Hartman Andrea N. , Karnopp Andrew , Adams Scott V. , Warren-Mears Victoria , Ramsey Scott D.
Published: April 2023

Abstract
Background: Little has been reported regarding patterns of oncologic care in American Indian/Alaska Natives (AI/AN). Observed worse survival has been attributed to later-stage presentation. We aimed to evaluate racial differences in cancer-directed therapy and hospice care utilization in AI/ANs and non-Hispanic whites (NHW) with metastatic cancer.

Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims database was accessed for AI/AN and NHW metastatic-cancer cases diagnosed between 2001 and 2007. Utilization of cancer-directed therapy (surgery, radiation, and/or chemotherapy) and/or hospice services was compared between AI/ANs and NHWs. Minimally adjusted (age, sex, diagnosis year) and fully-adjusted (also Klabunde comorbidity score, sociodemographic factors) regression models were used to estimate odds (OR) and hazard ratios (HR) for receipt of care.

Results: AI/ANs were younger, more likely to reside in the West, be unmarried, have lower income, and live in a nonurban setting than NHWs. Fewer AI/ANs received any cancer-directed therapy (57% vs. 61% NHWs) within 3 months of diagnosis; sociodemographic factors accounted for much of this difference [fully-adjusted HR, 0.94; 95% confidence interval (CI), 0.83–1.08]. We noted differences in hospice utilization between AI/ANs (52%) and NHWs (61%). A significant difference in hospice utilization remained after adjustment for sociodemographics (OR, 0.78; 95% CI, 0.61–0.99).

Conclusion: Observed absolute differences in care for AI/ANs and NHWs with metastatic cancer were largely accounted for by adjusting for socioeconomics, comorbidities, and demographic factors. A significant association between race and hospice utilization was noted.

Impact: Efforts to improve metastatic-cancer care should focus on socioeconomic barriers and investigate the observed disparity in receipt of hospice services. Cancer Epidemiol Biomarkers Prev; 24(7); 1138–43. ©2015 AACR.
Data from Risk of Precancer Determined by HPV Genotype Combinations in Women with Minor Cytologic Abnormalities
Authors: Gage Julia C. , Schiffman Mark , Solomon Diane , Wheeler Cosette M. , Gravitt Patti E. , Castle Philip E. , Wentzensen Nicolas
Published: April 2023

Abstract
Background: Studies suggest that testing for individual human papillomavirus (HPV) genotypes can improve risk stratification in women with minor cytologic abnormalities. We evaluated genotyping for HPV16, HPV16/18, and HPV16/18/45 in carcinogenic HPV-positive women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology.

Methods: For women enrolled in the ASCUS–LSIL Triage Study (ALTS), we calculated the age-stratified (<30 and 30+ years) positivity and cumulative risk over two years of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when testing positive or negative for three genotype combinations: HPV16, HPV16/18, and HPV16/18/45.

Results: Among women with ASCUS cytology, HPV16 positivity was 17.1% and increased to 22.0% (P < 0.001) for HPV16/18 and 25.6% (P < 0.001) for HPV16/18/45. Among women with LSIL cytology, HPV16 positivity was 21.1% and increased to 30.0% (P < 0.001) for HPV16/18 and 34.0% (P = 0.017) for HPV16/18/45. Regardless of cytology and age group, the greatest risk difference between test positives and test negatives was observed for HPV16 with decreasing risk stratification for HPV16/18 and HPV16/18/45. However, testing negative for any of the three combinations while being positive for another carcinogenic type still implied a two-year risk of CIN3+ of 7.8% or more.

Conclusions: Although genotyping for HPV16, 18, and 45 provided additional risk stratification in carcinogenic HPV-positive women with minor cytologic abnormalities, the risk among genotype-negative women was still high enough to warrant immediate colposcopy referral.

Impact: HPV genotyping in HPV-positive women with minor cytologic abnormalities will likely not alter clinical management. Adding HPV45 to genotyping assays is not warranted. Cancer Epidemiol Biomarkers Prev; 22(6); 1095–101. ©2013 AACR.
Data from A Comprehensive Meta-analysis of Case–Control Association Studies to Evaluate Polymorphisms Associated with the Risk of Differentiated Thyroid Carcinoma
Authors: Figlioli Gisella , Elisei Rossella , Romei Cristina , Melaiu Ombretta , Cipollini Monica , Bambi Franco , Chen Bowang , Köhler Aleksandra , Cristaudo Alfonso , Hemminki Kari , Gemignani Federica , Försti Asta , Landi Stefano
Published: April 2023

Abstract
Background: Linkage analyses and association studies suggested that inherited genetic variations play a role in the development of differentiated thyroid carcinoma (DTC).

Methods: We combined the results from a genome-wide association study (GWAS) performed by our group and from published studies on DTC. With a first approach, we evaluated whether a SNP published as associated with the risk of DTC could replicate in our GWAS (using FDR as adjustment for multiple comparisons). With the second approach, meta-analyses were performed between literature and GWAS when both sources suggested an association, increasing the statistical power of the analysis.

Results: rs1799814 (CYP1A1), rs1121980 (FTO), and 3 SNPs within 9q22 (rs965513, rs7048394, and rs894673) replicated the associations described in the literature. In addition, the meta-analyses between literature and GWAS revealed 10 more SNPs within 9q22, six within FTO, two within SOD1, and single variations within HUS1, WDR3, UGT2B7, ALOX12, TICAM1, ATG16L1, HDAC4, PIK3CA, SULF1, IL11RA, VEGFA, and 1p31.3, 2q35, 8p12, and 14q13.

Conclusion: This analysis confirmed several published risk loci that could be involved in DTC predisposition.

Impact: These findings provide evidence for the role of germline variants in DTC etiology and are consistent with a polygenic model of the disease. Cancer Epidemiol Biomarkers Prev; 25(4); 700–13. ©2016 AACR.
Data from Messages to Motivate Human Papillomavirus Vaccination: National Studies of Parents and Physicians
Authors: Malo Teri L. , Gilkey Melissa B. , Hall Megan E. , Shah Parth D. , Brewer Noel T.
Published: April 2023

Abstract
Background: Physician communication about human papillomavirus (HPV) vaccine is a key determinant of uptake. To support physician communication, we sought to identify messages that would motivate HPV vaccination.

Methods: From 2014 to 2015, we surveyed national samples of parents of adolescents ages 11 to 17 (n = 1,504) and primary care physicians (n = 776). Parents read motivational messages, selected from nine longer messages developed by the Centers for Disease Control and Prevention and six brief messages developed by the study team. Parents indicated whether each message would persuade them to get HPV vaccine for their adolescents. Physicians read the brief messages and indicated whether they would use them to persuade parents to get HPV vaccine for 11- to 12-year-old children.

Results: The highest proportion of parents (65%) and physicians (69%) found this brief message to be persuasive: “I strongly believe in the importance of this cancer-preventing vaccine for [child's name].” Parents disinclined to vaccinate were most receptive to messages with information about HPV infection being common, cancers caused by HPV, and HPV vaccine effectiveness. Parents' endorsement did not vary by race/ethnicity, education, child age, or child sex (all P > 0.05).

Conclusions: Our national surveys of parents and physicians identified messages that could motivate HPV vaccination, even among parents disinclined to vaccinate their children. The lack of difference across demographic subgroups in parental endorsement may suggest that these messages can be used across these subgroups.

Impact: Our findings support physicians' use of these messages with parents to help motivate uptake of this important cancer-preventing vaccine. Cancer Epidemiol Biomarkers Prev; 25(10); 1383–91. ©2016 AACR.
Data from Single-Nucleotide Polymorphisms in Nucleotide Excision Repair Genes, Cigarette Smoking, and the Risk of Head and Neck Cancer
Authors: Wyss Annah B. , Herring Amy H. , Avery Christy L. , Weissler Mark C. , Bensen Jeannette T. , Barnholtz-Sloan Jill S. , Funkhouser William K. , Olshan Andrew F.
Published: April 2023

Abstract
Background: Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC.

Methods: Using population-based case–control data from the Carolina Head and Neck Cancer Epidemiology (CHANCE) Study (1,227 cases and 1,325 controls), race-stratified (White, African American), conventional, and hierarchical logistic regression models were used to estimate ORs with 95% intervals (I) for the independent and joint effects of cigarette smoking and 84 single-nucleotide polymorphisms (SNP) from 15 NER genes on HNC risk.

Results: The odds of HNC were elevated among ever cigarette smokers and increased with smoking duration and frequency. Among Whites, rs4150403 on ERCC3 was associated with increased HNC odds (AA+AG vs. GG; OR, 1.28; 95% CI, 1.01–1.61). Among African Americans, rs4253132 on ERCC6 was associated with decreased HNC odds (CC+CT vs. TT; OR, 0.62; 95% CI, 0.45–0.86). Interactions between ever cigarette smoking and three SNPs (rs4253132 on ERCC6, rs2291120 on DDB2, and rs744154 on ERCC4) suggested possible departures from additivity among Whites.

Conclusions: We did not find associations between some previously studied NER variants and HNC. We did identify new associations between two SNPs and HNC and three suggestive cigarette–SNP interactions to consider in future studies.

Impact: We conducted one of the most comprehensive evaluations of NER variants, identifying a few SNPs from biologically plausible candidate genes associated with HNC and possibly interacting with cigarette smoking. Cancer Epidemiol Biomarkers Prev; 22(8); 1428–45. ©2013 AACR.
Data from Insurance-Based Differences in Time to Diagnostic Follow-up after Positive Screening Mammography
Authors: Durham Danielle D. , Robinson Whitney R. , Lee Sheila S. , Wheeler Stephanie B. , Reeder-Hayes Katherine E. , Bowling J. Michael , Olshan Andrew F. , Henderson Louise M.
Published: April 2023

Abstract
Background: Insurance may lengthen or inhibit time to follow-up after positive screening mammography. We assessed the association between insurance status and time to initial diagnostic follow-up after a positive screening mammogram.

Methods: Using 1995–2010 data from a North Carolina population-based registry of breast imaging and cancer outcomes, we identified women with a positive screening mammogram. We compared receipt of follow-up within 60 days of screening using logistic regression and evaluated time to follow-up initiation using Cox proportional hazards regression.

Results: Among 43,026 women included in the study, 73% were <65 years and 27% were 65+ years. Median time until initial diagnostic follow-up was similar by age group and insurance status. In the adjusted model for women <65, uninsured women experienced a longer time to initiation of diagnostic follow-up [HR, 0.47; 95% confidence interval (CI), 0.25–0.89] versus women with private insurance. There were increased odds of these uninsured women not meeting the Centers for Disease Control and Prevention guideline for follow-up within 60 days (OR, 1.59; 95% CI, 1.31–1.94). Among women ages 65+, women with private insurance experienced a faster time to follow-up (adjusted HR, 2.09; 95% CI, 1.27–3.44) than women with Medicare and private insurance. Approximately 10% of women had no follow-up by 365 days.

Conclusions: We found differences in time to initial diagnostic follow-up after a positive screening mammogram by insurance status and age group. Uninsured women younger than 65 years at a positive screening event had delayed follow-up.

Impact: Replication of these findings and examination of their clinical significance warrant additional investigation. Cancer Epidemiol Biomarkers Prev; 25(11); 1474–82. ©2016 AACR.
Data from Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Prizment Anna E. , Linabery Amy M. , Lutsey Pamela L. , Selvin Elizabeth , Nelson Heather H. , Folsom Aaron R. , Church Timothy R. , Drake Charles G. , Platz Elizabeth A. , Joshu Corinne
Published: April 2023

Abstract
Background: Serum β-2 microglobulin (B2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum B2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serum B2M is associated with risk of cancer (n = 2,436), including colorectal (n = 255), lung (n = 298), breast (n = 424), and prostate (n = 524) cancers, and hematological (n = 176) malignancies.

Methods: The analytical cohort (n = 12,300) was followed for incident cancers from 1990 through 2006. B2M (range, 0.9–57.8 mg/L) was measured in stored serum collected in 1990–1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of B2M.

Results: Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin, and hormone therapy (in women) and comparing highest to lowest B2M quartiles, HRs were 1.25 (1.06–1.47; Ptrend = 0.002) for total cancer risk and 2.21 (1.32–3.70; Ptrend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung, and hematological cancers.

Conclusions: These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk.

Impact: This study supports B2M as a potential biomarker for colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 25(4); 657–64. ©2016 AACR.
Data from Low-Dose CT Lung Cancer Screening Practices and Attitudes among Primary Care Providers at an Academic Medical Center
Authors: Lewis Jennifer A. , Petty W. Jeffrey , Tooze Janet A. , Miller David P. , Chiles Caroline , Miller Antonius A. , Bellinger Christina , Weaver Kathryn E.
Published: April 2023

Abstract
Background: Low-dose computed tomography (LDCT) screening reduces lung cancer–specific and overall mortality. We sought to assess lung cancer screening practices and attitudes among primary care providers (PCPs) in the era of new LDCT screening guidelines.

Methods: In 2013, we surveyed PCPs at an academic medical center (60% response) and assessed: lung cancer screening use, perceived screening effectiveness, knowledge of screening guidelines, perceived barriers to LDCT use, and interest in LDCT screening education.

Results: Few PCPs (n = 212) reported ordering lung cancer screening: chest X-ray (21%), LDCT (12%), and sputum cytology (3%). Only 47% of providers knew three or more of six guideline components for LDCT screening; 24% did not know any guideline components. In multiple logistic regression analysis, providers who knew three or more guideline components were more likely to order LDCT (OR, 7.1; 95% confidence intervals, 2.0–25.6). Many providers (30%) were unsure of the effectiveness of LDCT. Mammography, colonoscopy, and Pap smear were rated more frequently as effective in reducing cancer mortality compared with LDCT (all P values < 0.0001). Common perceived barriers included patient cost (86.9% major or minor barrier), harm from false positives (82.7%), patients' lack of awareness (81.3%), risk of incidental findings (81.3%), and insurance coverage (80.1%).

Conclusions: LDCT lung cancer screening is currently an uncommon practice at an academic medical center. PCPs report ordering chest X-ray, a nonrecommended screening test, more often than LDCT. PCPs had a limited understanding of lung cancer screening guidelines and LDCT effectiveness. Provider educational interventions are needed to facilitate shared decision-making with patients.

Impact: This study describes some of the first data available about PCPs' use of lung cancer screening tests since the publication of multiple professional guidelines endorsing LDCT. Knowledge gaps were identified that may hinder the uptake of evidence-based lung cancer screening guidelines. Cancer Epidemiol Biomarkers Prev; 24(4); 664–70. ©2015 AACR.
Data from Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort
Authors: Hudson Melissa M. , Ehrhardt Matthew J. , Bhakta Nickhill , Baassiri Malek , Eissa Hesham , Chemaitilly Wassim , Green Daniel M. , Mulrooney Daniel A. , Armstrong Gregory T. , Brinkman Tara M. , Klosky James L. , Krull Kevin R. , Sabin Noah D. , Wilson Carmen L. , Huang I-Chan , Bass Johnnie K. , Hale Karen , Kaste Sue , Khan Raja B. , Srivastava Deo Kumar , Yasui Yutaka , Joshi Vijaya M. , Srinivasan Saumini , Stokes Dennis , Hoehn Mary Ellen , Wilson Matthew , Ness Kirsten K. , Robison Leslie L.
Published: April 2023

Abstract
Characterization of toxicity associated with cancer and its treatment is essential to quantify risk, inform optimization of therapeutic approaches for newly diagnosed patients, and guide health surveillance recommendations for long-term survivors. The NCI Common Terminology Criteria for Adverse Events (CTCAE) provides a common rubric for grading severity of adverse outcomes in cancer patients that is widely used in clinical trials. The CTCAE has also been used to assess late cancer treatment-related morbidity but is not fully representative of the spectrum of events experienced by pediatric and aging adult survivors of childhood cancer. Also, CTCAE characterization does not routinely integrate detailed patient-reported and medical outcomes data available from clinically assessed cohorts. To address these deficiencies, we standardized the severity grading of long-term and late-onset health events applicable to childhood cancer survivors across their lifespan by modifying the existing CTCAE v4.03 criteria and aligning grading rubrics from other sources for chronic conditions not included or optimally addressed in the CTCAE v4.03. This article describes the methods of late toxicity assessment used in the St. Jude Lifetime Cohort Study, a clinically assessed cohort in which data from multiple diagnostic modalities and patient-reported outcomes are ascertained. Cancer Epidemiol Biomarkers Prev; 26(5); 666–74. ©2016 AACR.
Data from Multilevel Small-Area Estimation of Multiple Cigarette Smoking Status Categories Using the 2012 Behavioral Risk Factor Surveillance System
Authors: Berkowitz Zahava , Zhang Xingyou , Richards Thomas B. , Peipins Lucy , Henley S. Jane , Holt James
Published: April 2023

Abstract
Background: Smoking is the leading preventable cause of death; however, small-area estimates for detailed smoking status are limited. We developed multilevel small-area estimate mixed models to generate county-level estimates for six smoking status categories: current, some days, every day, former, ever, and never.

Method: Using 2012 Behavioral Risk Factor Surveillance System (BRFSS) data (our sample size = 405,233 persons), we constructed and fitted a series of multilevel logistic regression models and applied them to the U.S. Census population to generate county-level prevalence estimates. We mapped the estimates by sex and aggregated them into state and national estimates. We conducted comparisons for internal consistency with BRFSS states' estimates using Pearson correlation coefficients, and external validation with the 2012 National Health Interview Survey current smoking prevalence.

Results: Correlation coefficients ranged from 0.908 to 0.982, indicating high internal consistency. External validation indicated complete agreement (prevalence = 18.06%). We found large variations in current and former smoking status between and within states and by sex. County prevalence of former smokers was highest among men in the Northeast, North, and West. Utah consistently had the lowest smoking prevalence.

Conclusions: Our models, which include demographic and geographic characteristics, provide reliable estimates that can be applied to multiple category outcomes and any demographic group. County and state estimates may help understand the variation in smoking prevalence in the United States and provide information for control and prevention.

Impact: Detailed county and state smoking category estimates can help identify areas in need of tobacco control and prevention and potentially allow planning for health care. Cancer Epidemiol Biomarkers Prev; 25(10); 1402–10. ©2016 AACR.
Data from The Association between Leisure Time Physical Activity and Pancreatic Cancer Risk in Adults: A Systematic Review and Meta-analysis
Authors: Farris Megan S. , Mosli Mohammed H. , McFadden Alison A. , Friedenreich Christine M. , Brenner Darren R.
Published: April 2023

Abstract
We conducted a meta-analysis of the association between leisure time physical activity (LTPA) and risk of pancreatic cancer to update previous analyses in light of newly published studies, to examine subgroups of interest and potential sources of heterogeneity. We searched the PubMed and MEDLINE databases for studies until February 2015. Study information was collected using a standardized form to abstract relevant data on study design, number of cases, participant and study characteristics, assessment of LTPA, risk estimates, and adjustments for confounding by two independent abstractors. We used random-effects models to pool estimates from included studies of lowest versus highest comparison of LTPA. The search identified 26 studies eligible for inclusion into the meta-analysis. The combined summary risk estimate was [relative risk (RR), 0.89; 95% confidence interval (CI), 0.82–0.96]. There was evidence of heterogeneity across studies (I2 = 22.1%, Pheterogeneity = 0.130). Some of the heterogeneity could be explained by study design, with stronger protective effects observed among case–control studies (RR, 0.69; 95% CI, 0.59–0.81) compared with cohort studies (RR, 0.96; 95% CI, 0.91–1.02). Across study designs, age of population was a source of heterogeneity, with stronger effects observed among younger (<50 years) populations. The present meta-analysis supports a protective association between LTPA and pancreatic cancer with an 11% risk reduction observed. LTPA appears to have the strongest effect among young populations. Additional investigations are needed to provide insights regarding the impact of LTPA in healthy adult populations, to reduce the risk of pancreatic cancer and encourage increases in LTPA. Cancer Epidemiol Biomarkers Prev; 24(10); 1462–73. ©2015 AACR.
Data from Comparison of Associations of Body Mass Index, Abdominal Adiposity, and Risk of Colorectal Cancer in a Large Prospective Cohort Study
Authors: Keimling Marlen , Renehan Andrew G. , Behrens Gundula , Fischer Beate , Hollenbeck Albert R. , Cross Amanda J. , Leitzmann Michael F.
Published: April 2023

Abstract
Background: Increased body mass index (BMI) is an established colorectal cancer risk factor. High waist circumference or waist-hip-ratio (WHR) may better reflect an abnormal metabolic state and be more predictive of colorectal cancer risk than BMI.

Methods: We examined BMI, waist circumference, WHR, and hip circumference in relation to colorectal cancer risk among 203,177 participants followed for 10 years. We derived standardized colorectal cancer risk estimates for each anthropometric parameter and compared predictive characteristics (Harrell's C-index). In women, we examined whether hormone replacement therapy (HRT) use modified the associations between anthropometric measures and colorectal cancer.

Results: We ascertained 2,869 colorectal cancers. In men, increased colon cancer risks were associated with BMI [HR per SD, 1.14; 95% confidence interval (CI), 1.08–1.20], waist circumference (HR per SD, 1.17; 95% CI, 1.08–1.27), and WHR (HR per SD, 1.09; 95% CI, 1.04–1.14). In women, anthropometric variables were unrelated to colon cancer. For men and women, anthropometric variables were unrelated to rectal cancer. Compared with BMI, waist circumference and WHR did not materially influence colon cancer prediction models [C-index changes: −0.0041 and 0.0046 (men); 0.0004 and 0.0005 (women)]. In current HRT users, colon cancer was inversely or suggestively inversely associated with waist circumference (HR per SD, 0.78; 95% CI, 0.63–0.97) and WHR (HR per SD, 0.88; 95% CI, 0.76–1.01), but positively related to hip circumference (HR per SD, 1.39; 95% CI, 1.13–1.71).

Conclusion: BMI, waist circumference, and WHR show comparable positive associations with colon cancer in men. Associations between anthropometric measures and colon cancer are weak or null in women, but there is some evidence for effect modification by HRT.

Impact: These findings may improve our understanding of the relation of adiposity to colorectal cancer. Cancer Epidemiol Biomarkers Prev; 22(8); 1383–94. ©2013 AACR.
Data from Utility of Progranulin and Serum Leukocyte Protease Inhibitor as Diagnostic and Prognostic Biomarkers in Ovarian Cancer
Authors: Carlson Aaron M. , Maurer Matthew J. , Goergen Krista M. , Kalli Kimberly R. , Erskine Courtney L. , Behrens Marshall D. , Knutson Keith L. , Block Matthew S.
Published: April 2023

Abstract
Background: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in females and leading gynecologic cause of cancer-related death. Despite the identification of a number of serum biomarkers, methods to identify early-stage disease and predict prognosis remain scarce. We have evaluated two biologically connected serum biomarkers, serum leukocyte protease inhibitor (SLPI) and progranulin (PGRN).

Methods: Two-hundred frozen plasma samples were acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research. Samples were obtained from 50 patients with benign conditions, 50 with American Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III and IV EOC. Samples were obtained before surgical resection of a mass and were analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver-operator characteristic curves were generated for SLPI and PGRN. Median follow-up was 48 months.

Results: Absolute levels of SLPI were significantly elevated in patients with EOC compared with benign disease and predicted the presence of EOC (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with normal CA-125. PGRN levels were not significantly increased in patients with early-stage or late-stage EOC as a whole, but an increase in PGRN levels was associated with decreased overall survival in advanced EOC.

Conclusions: SLPI levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for patients with both elevated and normal CA-125 levels. An increase in PGRN is associated with decreased overall survival.

Impact: SLPI is elevated in EOC and warrants investigation in a screening study in women at risk for EOC. Cancer Epidemiol Biomarkers Prev; 22(10); 1730–5. ©2013 AACR.
Data from Menthol Smokers: Metabolomic Profiling and Smoking Behavior
Authors: Hsu Ping-Ching , Lan Renny S. , Brasky Theodore M. , Marian Catalin , Cheema Amrita K. , Ressom Habtom W. , Loffredo Christopher A. , Pickworth Wallace B. , Shields Peter G.
Published: April 2023

Abstract
Background: The use of menthol in cigarettes and marketing is under consideration for regulation by the FDA. However, the effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. We previously reported metabolomic profiling for cigarette smokers, and novelly identified a menthol-glucuronide (MG) as the most significant metabolite directly related to smoking. Here, MG is studied in relation to smoking behavior and metabolomic profiles.

Methods: This is a cross-sectional study of 105 smokers who smoked two cigarettes in the laboratory one hour apart. Blood nicotine, MG, and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). Spearman correlation, χ2, and ANCOVA adjusted for gender, race, and cotinine levels for menthol smokers assessed the relationship of MG boost, smoking behavior, and metabolic profiles. Multivariate metabolite characterization using supervised partial least squares-discriminant analysis (PLS-DA) was carried out for the classification of metabolomics profiles.

Results: MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Classification using PLS-DA, MG was the top metabolite discriminating metabolome of menthol versus nonmenthol smokers. Among menthol smokers, 42 metabolites were significantly correlated with MG boost, which linked to cellular functions, such as of cell death, survival, and movement.

Conclusions: Plasma MG boost is a new smoking behavior biomarker that may provide novel information over self-reported use of menthol cigarettes by integrating different smoking measures for understanding smoking behavior and harm of menthol cigarettes.

Impact: These results provide insight into the biological effect of menthol smoking. Cancer Epidemiol Biomarkers Prev; 26(1); 51–60. ©2016 AACR.
Data from Exploring Differences in the Aspirin–Colorectal Cancer Association by Sex and Race/Ethnicity: The Multiethnic Cohort Study
Authors: Park Song-Yi , Wilkens Lynne R. , Kolonel Laurence N. , Monroe Kristine R. , Haiman Christopher A. , Marchand Loïc Le
Published: April 2023

Abstract
Background: Evidence has accumulated that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer. We tested whether the inverse associations between NSAIDs and colorectal cancer is similarly observed across sexes and five racial/ethnic groups (Japanese, Latino, African American, Native Hawaiian, and white) in the Multiethnic Cohort (MEC) Study.

Methods: During a mean follow-up of 16.1 years, we identified 4,882 invasive incident colorectal cancer cases among 183,199 eligible participants. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI).

Results: Use of aspirin and other NSAIDs was associated with a lower incidence of colorectal cancer in men (HR = 0.77; 95% CI, 0.69–0.86 for current vs. never users of aspirin) but not in women (Pinteraction = 0.005). Among male current users, a reduced risk was observed with ≥6 years of aspirin or total NSAID use. The inverse association with current NSAID use in men was observed in all racial/ethnic groups, except for Native Hawaiians, and was stronger in whites.

Conclusions: Our findings suggest that the benefit of NSAIDs for colorectal cancer may be strongest for white men and generalizes to African American, Japanese, and Latino, but not to Native Hawaiian men. The lack of inverse association observed in women and Native Hawaiian men in the MEC should be interpreted with caution.

Impact: As only very few ethnic/racial groups are likely to be represented in trials of NSAIDs and colorectal cancer, it is important to conduct prospective observational studies in various populations to test the generalizability of their results. Cancer Epidemiol Biomarkers Prev; 26(2); 162–9. ©2016 AACR.
Data from Exposure to Heavy Metals and Polycyclic Aromatic Hydrocarbons and DNA Damage in Taiwanese Traffic Conductors
Authors: Huang Han-Bin , Chen Guan-Wen , Wang Chien-Jen , Lin Yong-Yang , Liou Saou-Hsing , Lai Ching-Huang , Wang Shu-Li
Published: April 2023

Abstract
Background: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAH) and heavy metals, has been associated with the etiology and prognosis of many illnesses. However, the specific causal agents and underlying mechanisms for different health outcomes remain unclear. The aims of this study were to assess the relations between urinary biomarkers of exposure to PAHs (1-hydroxypyrene-glucuronide, 1-OHPG) and heavy metals (cadmium, Cd; nickel, Ni; arsenic, As; lead, Pb; and copper, Cu) and the effect of their interaction on DNA damage (8-oxo-7,8-dihydro-guanine, 8-oxodG).

Methods: We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei, Taiwan. Postshift urine samples from 2 consecutive days were analyzed for 1-OHPG, Cd, Ni, As, Pb, Cu, and 8-oxodG. To estimate the effects from PAHs and metals on DNA damage, we constructed a linear mixed model adjusted for confounding variables.

Results: We found that urinary 1-OHPG and Cd levels were independent predictors of urinary 8-oxodG levels (β = 0.112; P = 0.015 for 1-OHPG; β = 0.138; P = 0.031 for urinary Cd). The joint effect of urinary 1-OHPG and Cd levels was associated with urinary 8-oxodG levels (P = 0.001).

Conclusions: Co-exposure to environmental PAHs and Cd could cause oxidative DNA damage.

Impact: These findings suggest that the additive interaction between exposure to environmental PAHs and Cd could enhance the burden of oxidative stress. Cancer Epidemiol Biomarkers Prev; 22(1); 102–8. ©2012 AACR.
Data from Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk
Authors: Vendrame Elena , Hussain Shehnaz K. , Breen Elizabeth Crabb , Magpantay Larry I. , Widney Daniel P. , Jacobson Lisa P. , Variakojis Daina , Knowlton Emilee R. , Bream Jay H. , Ambinder Richard F. , Detels Roger , Martínez-Maza Otoniel
Published: April 2023

Abstract
Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood.

Methods: In this study, serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1 to 5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS).

Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), interleukin (IL)-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α were elevated in those HIV+ individuals who went on to develop AIDS-NHL. In addition, the fraction of specimens with detectable IL-2 was increased and the fraction with detectable IL-4 was decreased in these subjects.

Conclusions: These results suggest that long-term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals.

Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α may serve as biomarkers for AIDS-NHL. Cancer Epidemiol Biomarkers Prev; 23(2); 343–9. ©2013 AACR.
Data from Maternal Smoking and DNA Methylation in Newborns: In Utero Effect or Epigenetic Inheritance?
Authors: Joubert Bonnie R. , Håberg Siri E. , Bell Douglas A. , Nilsen Roy M. , Vollset Stein Emil , Midttun Øivind , Ueland Per Magne , Wu Michael C. , Nystad Wenche , Peddada Shyamal D. , London Stephanie J.
Published: April 2023

Abstract
Background: Maternal smoking in pregnancy is associated with adverse health outcomes in children, including cancers; underlying mechanisms may include epigenetic modifications. Using Illumina's 450K array, we previously identified differential DNA methylation related to maternal smoking during pregnancy at 26 CpG sites (CpGs) in 10 genes in newborn cord bloods from the Norwegian Mother and Child Cohort Study (MoBa). Whether these methylation signals in newborns reflect in utero exposure only or possibly epigenetic inheritance of smoking-related modifications is unclear.

Methods: We therefore evaluated the impact of the timing of mother's smoking (before or during pregnancy using cotinine measured at 18 weeks gestation), the father's smoking before conception, and the grandmother's smoking during her pregnancy with the mother on methylation at these 26 CpGs in 1,042 MoBa newborns. We used robust linear regression, adjusting for covariates, applying Bonferroni correction.

Results: The strongest and only statistically significant associations were observed for sustained smoking by the mother during pregnancy through at least gestational week 18 (P < 1.6 × 10−5 for all 26 CpGs). We observed no statistically significant differential methylation due to smoking by the mother before pregnancy or that ceased by week 18, father's smoking before conception, or grandmother's smoking while pregnant with the mother.

Conclusions: Differential methylation at these CpGs in newborns seems to reflect sustained in utero exposure rather than epigenetic inheritance.

Impact: Smoking cessation in early pregnancy may negate effects on methylation. Analyses of maternal smoking during pregnancy and offspring health outcomes, including cancer, limited to ever smoking might miss true associations. Cancer Epidemiol Biomarkers Prev; 23(6); 1007–17. ©2014 AACR.
Data from Construction and Analysis of the NCI-EDRN Breast Cancer Reference Set for Circulating Markers of Disease
Authors: Marks Jeffrey R. , Anderson Karen S. , Engstrom Paul , Godwin Andrew K. , Esserman Laura J. , Longton Gary , Iversen Edwin S. , Mathew Anu , Patriotis Christos , Pepe Margaret S.
Published: April 2023

Abstract
Background: Many circulating biomarkers have been reported for the diagnosis of breast cancer, but few, if any, have undergone rigorous credentialing using prospective cohorts and blinded evaluation.

Methods: The NCI Early Detection Research Network (EDRN) has created a prospective, multicenter collection of plasma and serum samples from 832 subjects designed to evaluate circulating biomarkers for the detection and diagnosis of breast cancer. These samples are available to investigators who wish to evaluate their biomarkers using a set of blinded samples. The breast cancer reference set is composed of blood samples collected using a standard operating procedure at four U.S. medical centers from 2008 to 2010 from women undergoing either tissue diagnosis for breast cancer or routine screening mammography. The reference set contains samples from women with incident invasive cancer (n = 190), carcinoma in situ (n = 55), benign pathology with atypia (n = 63), benign disease with no atypia (n = 231), and women with no evidence of breast disease by screening mammography (BI-RADS 1 or 2, n = 276). Using a subset of plasma samples (n = 505) from the reference set, we analyzed 90 proteins by multiplexed immunoassays for their potential utility as diagnostic markers.

Results: We found that none of these markers is useful for distinguishing cancer from benign controls. However, elevated CA-125 does appear to be a candidate marker for estrogen receptor–negative cancers.

Conclusions: Markers that can distinguish benign breast conditions from invasive cancer have not yet been found.

Impact: Availability of prospectively collected samples should improve future validation efforts. Cancer Epidemiol Biomarkers Prev; 24(2); 435–41. ©2014 AACR.
Data from De Novo Post-Diagnosis Aspirin Use and Mortality in Women with Stage I–III Breast Cancer
Authors: Barron Thomas I. , Murphy Laura M. , Brown Chris , Bennett Kathleen , Visvanathan Kala , Sharp Linda
Published: April 2023

Abstract
Background: Aspirin use has been associated with significant reductions in breast cancer–related mortality in some observational studies. However, these studies included women who initiated aspirin use before breast cancer diagnosis. It is unclear whether initiating aspirin use after diagnosis is associated with similar reductions in mortality. This study investigates associations between de novo post-diagnostic aspirin use and all cause, breast cancer–specific mortality.

Methods: Women, ages 50 to 80, with a diagnosis of stage I–III breast cancer were identified from Ireland's National Cancer Registry (N = 4,540). Initiation of de novo post-diagnostic aspirin use was identified from linked national prescription refill data (N = 764). Adjusted HRs were estimated for associations between de novo aspirin use and all-cause, breast cancer–specific mortality.

Results: The median time from diagnosis to aspirin initiation was 1.8 years. The mean number of days' supply of aspirin received was 631, and 95% of users were taking less than 150 mg/d. We found no association between de novo aspirin use and breast cancer–specific mortality [HR, 0.98; 95% confidence interval (CI), 0.74–1.30]. Similar null associations were found in women taking aspirin at high-intensity (HR, 1.03; 95% CI, 0.72–1.47) and women initiating use in the 1.5 years after diagnosis (HR, 1.04; 95% CI, 0.77–1.40). There was no effect modification by estrogen (Pinteraction = 0.81) or progesterone (Pinteraction = 0.41) receptor status.

Conclusion: Initiating aspirin use after a breast cancer diagnosis was not associated with a reduction in breast cancer–specific mortality.

Impact: On the basis of our findings, we suggest that a clearer understanding of aspirin's mechanism of action is needed to help inform the design of future studies in breast cancer. Cancer Epidemiol Biomarkers Prev; 24(6); 898–904. ©2015 AACR.
Data from Investigation of Epstein–Barr Virus as a Potential Cause of B-Cell Non-Hodgkin Lymphoma in a Prospective Cohort
Authors: De Roos Anneclaire J. , Martínez-Maza Otoniel , Jerome Keith R. , Mirick Dana K. , Kopecky Kenneth J. , Madeleine Margaret M. , Magpantay Larry , Edlefsen Kerstin L. , LaCroix Andrea Z.
Published: April 2023

Abstract
Background: We hypothesized that poor control of Epstein–Barr virus (EBV) infection, leading to reactivation of the virus, increases the risk of non-Hodgkin lymphoma (NHL) in the general population of primarily immunocompetent persons.

Methods: We conducted a case–control study nested within the Women's Health Initiative Observational Study cohort in which we measured antibodies to EBV antigens [immunoglobulin G (IgG) to viral capsid antigen (VCA), nuclear antigen (EBNA1), and early antigen-diffuse (EA-D)] and EBV DNA load in prediagnostic samples of 491 B-cell NHL cases and 491 controls.

Results: We found no association with established EBV infection, based on seropositivity for VCA. Seropositivity for EBNA1 was associated with decreased risk of B-cell NHL, overall [OR = 0.5; 95% confidence interval (CI), 0.3–0.8] and for each of the histologic subtypes examined. Increased risk of chronic lymphocytic leukemia (CLL) and related subtypes was observed with higher levels of EBV DNA and antibody to EA-D, both markers reflective of reactivation. These associations were strongest for cases with the shortest time interval between blood draw and diagnosis.

Conclusions: In balance, these results do not provide strong evidence of EBV playing a causal role in B-cell NHL in general population women. The associations we observed may reflect increased risk of NHL with underlying immune impairment or could be due to reverse causation.

Impact: Further characterization of the subtype-specific association with CLL is warranted. Exclusion of cases with preclinical disease markers (such as monoclonal B-lymphocytosis for CLL) may help rule out reverse causation in future studies. Cancer Epidemiol Biomarkers Prev; 22(10); 1747–55. ©2013 AACR.