bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from The Epidemic of Non–Hodgkin Lymphoma in the United States: Disentangling the Effect of HIV, 1992–2009
Authors: Shiels Meredith S. , Engels Eric A. , Linet Martha S. , Clarke Christina A. , Li Jianmin , Hall H. Irene , Hartge Patricia , Morton Lindsay M.
Published: April 2023

Abstract
Background: For decades, non–Hodgkin lymphoma (NHL) incidence has been increasing worldwide. NHL risk is strongly increased among HIV-infected people. Our understanding of trends in NHL incidence has been hampered by difficulties in separating HIV-infected NHL cases from general population rates.

Methods: NHL incidence data during 1992–2009 were derived from 10 U.S. SEER cancer registries with information on HIV status at NHL diagnosis. The CDC estimated the number of people living with HIV in the registry areas. The proportion of NHL cases with HIV and NHL rates in the total and the HIV-uninfected populations were estimated. Time trends were assessed with Joinpoint analyses.

Results: Of 115,643 NHL cases diagnosed during 1992–2009, 5.9% were HIV-infected. The proportions of NHL cases with HIV were highest for diffuse large B-cell (DLBCL; 7.8%), Burkitt (26.9%), and peripheral T-cell lymphomas (3.2%) with low proportions (≤1.1%) in the other subtypes. NHL rates in the total population increased 0.3% per year during 1992–2009. However, rates of NHL in HIV-uninfected people increased 1.4% per year during 1992–2003, before becoming stable through 2009. Similar trends were observed for DLBCLs and follicular lymphoma in HIV-uninfected people; rates increased 2.7% per year until 2003 and 1.7% per year until 2005, respectively, before stabilizing.

Conclusions: NHL incidence rates in the United States have plateaued over the last 5–10 years, independent of HIV infection.

Impact: Although the causes of the long-term increase in NHL incidence rates in the United States remain unknown, general population rates of NHL have stabilized since the early 2000s, independent of HIV. Cancer Epidemiol Biomarkers Prev; 22(6); 1069–78. ©2013 AACR.
Data from Childhood Height and Birth Weight in Relation to Future Prostate Cancer Risk: A Cohort Study Based on the Copenhagen School Health Records Register
Authors: Cook Michael B. , Gamborg Michael , Aarestrup Julie , Sørensen Thorkild I.A. , Baker Jennifer L.
Published: April 2023

Abstract
Background: Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR).

Methods: The CSHRR comprises 372,636 school children. For boys born between the 1930s and 1969, birth weight and annual childhood heights—measured between ages 7 and 13 years—were analyzed in relation to prostate cancer risk. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI).

Results: There were 125,211 males for analysis, 2,987 of who were subsequently diagnosed with prostate cancer during 2.57 million person-years of follow-up. Height z-score was significantly associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at age 13 years was more important than height change (P = 0.024) and height at age 7 years (P = 0.024), when estimates from mutually adjusted models were compared. Adjustment of birth weight did not alter the estimates. Birth weight was not associated with prostate cancer risk.

Conclusions: The association between childhood height and prostate cancer risk was driven by height at age 13 years.

Impact: Our findings implicate late childhood, adolescence, and adulthood growth periods as containing the exposure window(s) of interest that underlies the association between height and prostate cancer. The causal factor may not be singular given the complexity of both human growth and carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(12); 2232–40. ©2013 AACR.
Data from Menthol Cigarettes, Race/Ethnicity, and Biomarkers of Tobacco Use in U.S. Adults: The 1999–2010 National Health and Nutrition Examination Survey (NHANES)
Authors: Jones Miranda R. , Apelberg Benjamin J. , Tellez-Plaza Maria , Samet Jonathan M. , Navas-Acien Ana
Published: April 2023

Abstract
Background: In the United States, cigarette flavorings are banned, with the exception of menthol. The cooling effects of menthol could facilitate the absorption of tobacco toxicants. We examined levels of biomarkers of tobacco exposure among U.S. smokers of menthol and nonmenthol cigarettes.

Methods: We studied 4,603 White, African-American, and Mexican-American current smokers 20 years of age or older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2010 and had data on cigarette type and serum cotinine, blood cadmium, and blood lead concentrations. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL) was studied in 1,607 participants with available measures.

Results: A total of 3,210 (74.3%) participants smoked nonmenthol cigarettes compared with 1,393 (25.7%) participants who smoked menthol cigarettes. The geometric mean concentrations comparing smokers of nonmenthol with menthol cigarettes were 163.1 versus 175.9 ng/mL for serum cotinine; 0.95 versus 1.02 μg/L for blood cadmium; 1.87 versus 1.75 μg/dL for blood lead; and 0.27 versus 0.23 ng/mL for urine NNAL. After multivariable adjustment, the ratios [95% confidence interval (CI)] comparing smokers of menthol with nonmenthol cigarettes were 1.03 (0.95–1.11) for cotinine, 1.10 (1.04–1.16) for cadmium, 0.95 (0.90–1.01) for lead, and 0.81 (0.65–1.01) for NNAL.

Conclusions: In a representative sample of U.S. adult smokers, current menthol cigarette use was associated with increased concentration of blood cadmium, an established carcinogen and highly toxic metal, but not with other biomarkers.

Impact: These findings provide information regarding possible differences in exposure to toxic constituents among menthol cigarette smokers compared with nonmenthol cigarette smokers. Cancer Epidemiol Biomarkers Prev; 22(2); 224–32. ©2012 AACR.
Data from Increased Levels of Tetra-antennary N-Linked Glycan but Not Core Fucosylation Are Associated with Hepatocellular Carcinoma Tissue
Authors: Mehta Anand , Norton Pamela , Liang Hongyan , Comunale Mary Ann , Wang Mengjun , Rodemich-Betesh Lucy , Koszycki Alex , Noda Katsuhisa , Miyoshi Eiji , Block Timothy
Published: April 2023

Abstract
Background: Alterations in glycosylation have long been associated with the development of cancer. In the case of primary hepatocellular carcinoma (HCC), one alteration that has often been associated is increased amounts of fucose attached to the N-glycans of serum proteins secreted by the liver.

Methods: In an effort to determine the origin of this increased fucosylation, we have conducted N-linked glycan analysis of HCC tissue, the surrounding nontumor tissue, and compared this to tissue from a nondiseased adult liver.

Results: Surprisingly, no difference in the level of fucosylation was observed from the three donor groups, suggesting that the increased levels of fucosylation observed in serum of those with HCC is not the result of increased synthesis of fucosylated proteins in the cancer tissue. On the other hand, increased levels of a tetra-antennary glycan were observed in the HCC tissue as compared with the surrounding tissue or to the nondiseased livers.

Conclusions: This represents, to our knowledge, one of the first reports associating increased levels of branching with the development of HCC.

Impact: The identification of increased levels of tetra-antennary glycan on liver tumor tissue, as opposed to adjacent or nondiseased tissue may lead to improved detection of HCC. Cancer Epidemiol Biomarkers Prev; 21(6); 925–33. ©2012 AACR.
Data from Prediagnostic Levels of Serum One-Carbon Metabolites and Risk of Hepatocellular Carcinoma
Authors: Butler Lesley M. , Arning Erland , Wang Renwei , Bottiglieri Teodoro , Govindarajan Sugantha , Gao Yu-Tang , Yuan Jian-Min
Published: April 2023

Abstract
Background: Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking.

Methods: We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case–control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma.

Results: Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, and SAM were associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16–0.78; P = 0.010) and 0.44 (0.25–0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine.

Conclusion: The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation.

Impact: Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted. Cancer Epidemiol Biomarkers Prev; 22(10); 1884–93. ©2013 AACR.
Data from Postdiagnosis Weight Change and Survival Following a Diagnosis of Early-Stage Breast Cancer
Authors: Cespedes Feliciano Elizabeth M. , Kroenke Candyce H. , Bradshaw Patrick T. , Chen Wendy Y. , Prado Carla M. , Weltzien Erin K. , Castillo Adrienne L. , Caan Bette J.
Published: April 2023

Abstract
Background: Achieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results.

Methods: We examined whether change in body weight in the 18 months following diagnosis is associated with overall and breast cancer–specific mortality in a cohort of n = 12,590 stage I–III breast cancer patients at Kaiser Permanente using multivariable-adjusted Cox regression models. Follow-up was from the date of the postdiagnosis weight at 18 months until death or June 2015 [median follow-up (range): 3 (0–9) years]. We divided follow-up into earlier (18–54 months) and later (>54 months) postdiagnosis periods.

Results: Mean (SD) age-at-diagnosis was 59 (11) years. A total of 980 women died, 503 from breast cancer. Most women maintained weight within 5% of diagnosis body weight; weight loss and gain were equally common at 19% each. Compared with weight maintenance, large losses (≥10%) were associated with worse survival, with HRs and 95% confidence intervals (CI) for all-cause death of 2.63 (2.12–3.26) earlier and 1.60 (1.14–2.25) later in follow-up. Modest losses (>5%–<10%) were associated with worse survival earlier [1.39 (1.11–1.74)] but not later in follow-up [0.77 (0.54–1.11)]. Weight gain was not related to survival. Results were similar for breast cancer–specific death.

Conclusion: Large postdiagnosis weight loss is associated with worse survival in both earlier and later postdiagnosis periods, independent of treatment and prognostic factors.

Impact: Weight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk. Cancer Epidemiol Biomarkers Prev; 26(1); 44–50. ©2016 AACR.

See all the articles in this CEBP Focus section, “The Obesity Paradox in Cancer: Evidence and New Directions.”
Data from Metabolomic Characterization of Hepatocellular Carcinoma in Patients with Liver Cirrhosis for Biomarker Discovery
Authors: Di Poto Cristina , Ferrarini Alessia , Zhao Yi , Varghese Rency S. , Tu Chao , Zuo Yiming , Wang Minkun , Nezami Ranjbar Mohammad R. , Luo Yue , Zhang Chi , Desai Chirag S. , Shetty Kirti , Tadesse Mahlet G. , Ressom Habtom W.
Published: April 2023

Abstract
Background: Metabolomics plays an important role in providing insight into the etiology and mechanisms of hepatocellular carcinoma (HCC). This is accomplished by a comprehensive analysis of patterns involved in metabolic alterations in human specimens. This study compares the levels of plasma metabolites in HCC cases versus cirrhotic patients and evaluates the ability of candidate metabolites in distinguishing the two groups. Also, it investigates the combined use of metabolites and clinical covariates for detection of HCC in patients with liver cirrhosis.

Methods: Untargeted analysis of metabolites in plasma from 128 subjects (63 HCC cases and 65 cirrhotic controls) was conducted using gas chromatography coupled to mass spectrometry (GC-MS). This was followed by targeted evaluation of selected metabolites. LASSO regression was used to select a set of metabolites and clinical covariates that are associated with HCC. The performance of candidate biomarkers in distinguishing HCC from cirrhosis was evaluated through a leave-one-out cross-validation based on area under the receiver operating characteristics (ROC) curve.

Results: We identified 11 metabolites and three clinical covariates that differentiated HCC cases from cirrhotic controls. Combining these features in a panel for disease classification using support vector machines (SVM) yielded better area under the ROC curve compared with alpha-fetoprotein (AFP).

Conclusions: This study demonstrates the combination of metabolites and clinical covariates as an effective approach for early detection of HCC in patients with liver cirrhosis.

Impact: Further investigation of these findings may improve understanding of HCC pathophysiology and possible implication of the metabolites in HCC prevention and diagnosis. Cancer Epidemiol Biomarkers Prev; 26(5); 675–83. ©2016 AACR.
Data from Germline Missense Variants in the BTNL2 Gene Are Associated with Prostate Cancer Susceptibility
Authors: FitzGerald Liesel M. , Kumar Akash , Boyle Evan A. , Zhang Yuzheng , McIntosh Laura M. , Kolb Suzanne , Stott-Miller Marni , Smith Tiffany , Karyadi Danielle M. , Ostrander Elaine A. , Hsu Li , Shendure Jay , Stanford Janet L.
Published: April 2023

Abstract
Background: Rare, inherited mutations account for 5% to 10% of all prostate cancer cases. However, to date, few causative mutations have been identified.

Methods: To identify rare mutations for prostate cancer, we conducted whole-exome sequencing (WES) in multiple kindreds (n = 91) from 19 hereditary prostate cancer (HPC) families characterized by aggressive or early-onset phenotypes. Candidate variants (n = 130) identified through family- and bioinformatics-based filtering of WES data were then genotyped in an independent set of 270 HPC families (n = 819 prostate cancer cases; n = 496 unaffected relatives) for replication. Two variants with supportive evidence were subsequently genotyped in a population-based case–control study (n = 1,155 incident prostate cancer cases; n = 1,060 age-matched controls) for further confirmation. All participants were men of European ancestry.

Results: The strongest evidence was for two germline missense variants in the butyrophilin-like 2 (BTNL2) gene (rs41441651, p.Asp336Asn and rs28362675, p.Gly454Cys) that segregated with affection status in two of the WES families. In the independent set of 270 HPC families, 1.5% (rs41441651; P = 0.0032) and 1.2% (rs28362675; P = 0.0070) of affected men, but no unaffected men, carried a variant. Both variants were associated with elevated prostate cancer risk in the population-based study (rs41441651: OR, 2.7; 95% CI, 1.27–5.87; P = 0.010; rs28362675: OR, 2.5; 95% CI, 1.16–5.46; P = 0.019).

Conclusions: Results indicate that rare BTNL2 variants play a role in susceptibility to both familial and sporadic prostate cancer.

Impact: Results implicate BTNL2 as a novel prostate cancer susceptibility gene. Cancer Epidemiol Biomarkers Prev; 22(9); 1520–8. ©2013 AACR.
Data from Multistage Analysis of Variants in the Inflammation Pathway and Lung Cancer Risk in Smokers
Authors: Spitz Margaret R. , Gorlov Ivan P. , Dong Qiong , Wu Xifeng , Chen Wei , Chang David W. , Etzel Carol J. , Caporaso Neil E. , Zhao Yang , Christiani David C. , Brennan Paul , Albanes Demetrius , Shi Jianxin , Thun Michael , Landi Maria Teresa , Amos Christopher I.
Published: April 2023

Abstract
Background: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer.

Methods: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case–control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication.

Results: There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case–control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs.

Conclusions/Impact: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. Cancer Epidemiol Biomarkers Prev; 21(7); 1213–21. ©2012 AACR.
Data from Solid Tumors of Childhood Display Specific Serum microRNA Profiles
Authors: Murray Matthew J. , Raby Katie L. , Saini Harpreet K. , Bailey Shivani , Wool Sophie V. , Tunnacliffe Jane M. , Enright Anton J. , Nicholson James C. , Coleman Nicholas
Published: April 2023

Abstract
Background: Serum biomarkers for diagnosis and risk stratification of childhood solid tumors would improve the accuracy/timeliness of diagnosis and reduce the need for invasive biopsies. We hypothesized that differential expression and/or release of microRNAs (miRNAs) by such tumors may be detected as altered serum miRNA profiles.

Methods: We undertook global quantitative reverse transcription PCR (qRT-PCR) miRNA profiling (n = 741) on RNA from 53 serum samples, representing 33 diagnostic cases of common childhood cancers plus 20 controls. Technical confirmation was performed in a subset of 21 cases, plus four independent samples.

Results: We incorporated robust quality control steps for RNA extraction, qRT-PCR efficiency and hemolysis quantification. We evaluated multiple methods to normalize global profiling data and identified the ‘global mean’ approach as optimal. We generated a panel of six miRNAs that were most stable in pediatric serum samples and therefore most suitable for normalization of targeted miRNA qRT-PCR data. Tumor-specific serum miRNA profiles were identified for each tumor type and selected miRNAs underwent confirmatory testing. We identified a panel of miRNAs (miR-124-3p/miR-9-3p/miR-218-5p/miR-490-5p/miR-1538) of potential importance in the clinical management of neuroblastoma, as they were consistently highly overexpressed in MYCN-amplified high-risk cases (MYCN-NB). We also derived candidate miRNA panels for noninvasive differential diagnosis of a liver mass (hepatoblastoma vs. combined MYCN-NB/NB), an abdominal mass (Wilms tumor vs. combined MYCN-NB/NB), and sarcoma subtypes.

Conclusions: This study describes a pipeline for robust diagnostic serum miRNA profiling in childhood solid tumors, and has identified candidate miRNA profiles for prospective testing.

Impact: We propose a new noninvasive method with the potential to diagnose childhood solid tumors. Cancer Epidemiol Biomarkers Prev; 24(2); 350–60. ©2014 AACR.
Data from Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk
Authors: Lee Eunjung , Stram Daniel O. , Ek Weronica E. , Onstad Lynn E. , MacGregor Stuart , Gharahkhani Puya , Ye Weimin , Lagergren Jesper , Shaheen Nicholas J. , Murray Liam J. , Hardie Laura J. , Gammon Marilie D. , Chow Wong-Ho , Risch Harvey A. , Corley Douglas A. , Levine David M. , Whiteman David C. , Bernstein Leslie , Bird Nigel C. , Vaughan Thomas L. , Wu Anna H.
Published: April 2023

Abstract
Background: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.

Methods: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.

Results: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.

Conclusions: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus.

Impact: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus. Cancer Epidemiol Biomarkers Prev; 24(11); 1801–3. ©2015 AACR.
Data from Prediagnostic 25-Hydroxyvitamin D, VDR and CASR Polymorphisms, and Survival in Patients with Colorectal Cancer in Western European Populations
Authors: Fedirko Veronika , Riboli Elio , Tjønneland Anne , Ferrari Pietro , Olsen Anja , Bueno-de-Mesquita H. Bas , van Duijnhoven Fränzel J.B. , Norat Teresa , Jansen Eugène H.J.M. , Dahm Christina C. , Overvad Kim , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Racine Antoine , Lukanova Annekatrin , Teucher Birgit , Boeing Heiner , Aleksandrova Krasimira , Trichopoulou Antonia , Benetou Vassiliki , Trichopoulos Dimitrios , Grioni Sara , Vineis Paolo , Panico Salvatore , Palli Domenico , Tumino Rosario , Siersema Peter D. , Peeters Petra H. , Skeie Guri , Brustad Magritt , Chirlaque Maria-Dolores , Barricarte Aurelio , Ramón Quirós Jose , Sánchez Maria José , Dorronsoro Miren , Bonet Catalina , Palmqvist Richard , Hallmans Göran , Key Timothy J. , Crowe Francesca , Khaw Kay-Tee , Wareham Nick , Romieu Isabelle , McKay James , Wark Petra A. , Romaguera Dora , Jenab Mazda
Published: April 2023

Abstract
Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown.

Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N = 444) and overall mortality (N = 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated.

Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend = 0.04) and overall mortality (Ptrend = 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction = 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival.

Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC.

Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients. Cancer Epidemiol Biomarkers Prev; 21(4); 582–93. ©2012 AACR.
Data from A Nomogram Derived by Combination of Demographic and Biomarker Data Improves the Noninvasive Evaluation of Patients at Risk for Bladder Cancer
Authors: Huang Sijia , Kou Lei , Furuya Hideki , Yu Changhong , Goodison Steve , Kattan Michael W. , Garmire Lana , Rosser Charles J.
Published: April 2023

Abstract
Background: Improvements in the noninvasive clinical evaluation of patients at risk for bladder cancer would be of benefit both to individuals and to health care systems. We investigated the potential utility of a hybrid nomogram that combined key demographic features with the results of a multiplex urinary biomarker assay in hopes of identifying patients at risk of harboring bladder cancer.

Methods: Logistic regression analysis was used to model the probability of bladder cancer burden in a cohort of 686 subjects (394 with bladder cancer) using key demographic features alone, biomarker data alone, and the combination of demographic features and key biomarker data. We examined discrimination, calibration, and decision curve analysis techniques to evaluate prediction model performance.

Results: Area under the receiver operating characteristic curve (AUC) analyses revealed that demographic features alone predicted tumor burden with an accuracy of 0.806 [95% confidence interval (CI), 0.76–0.85], while biomarker data had an accuracy of 0.835 (95% CI, 0.80–0.87). The addition of molecular data into the nomogram improved the predictive performance to 0.891 (95% CI, 0.86–0.92). Decision curve analyses showed that the hybrid nomogram performed better than demographic or biomarker data alone.

Conclusion: A nomogram construction strategy that combines key demographic features with biomarker data may facilitate the accurate, noninvasive evaluation of patients at risk of harboring bladder cancer. Further research is needed to evaluate the bladder cancer risk nomogram for potential clinical utility.

Impact: The application of such a nomogram may better inform the decision to perform invasive diagnostic procedures. Cancer Epidemiol Biomarkers Prev; 25(9); 1361–6. ©2016 AACR.
Data from Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined
Authors: Heijnsdijk Eveline A.M. , Warner Ellen , Gilbert Fiona J. , Tilanus-Linthorst Madeleine M.A. , Evans Gareth , Causer Petrina A. , Eeles Rosalind A. , Kaas Reinie , Draisma Gerrit , Ramsay Elizabeth A. , Warren Ruth M.L. , Hill Kimberly A. , Hoogerbrugge Nicoline , Wasser Martin N.J.M. , Bergers Elisabeth , Oosterwijk Jan C. , Hooning Maartje J. , Rutgers Emiel J.T. , Klijn Jan G.M. , Plewes Don B. , Leach Martin O. , de Koning Harry J.
Published: April 2023

Abstract
Background: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines.

Methods: Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality.

Results:BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening.

Conclusions: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history.

Impact: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40. Cancer Epidemiol Biomarkers Prev; 21(9); 1458–68. ©2012 AACR.
Data from The Association between Alcohol Consumption and Breast Density: A Systematic Review and Meta-analysis
Authors: Ziembicki Stephanie , Zhu Jie , Tse Elizabeth , Martin Lisa J. , Minkin Salomon , Boyd Norman F.
Published: April 2023

Abstract
Background: Percent breast density (PBD) is a strong risk factor for breast cancer that is influenced by several other risk factors for the disease. Alcohol consumption is associated with an increased risk of breast cancer with an uncertain association with PBD. We have carried out a systematic review and meta-analysis to examine the association of alcohol consumption with PBD.

Methods: We searched nine databases to identify all relevant studies on the association between alcohol intake and breast density. Two independent investigators evaluated and selected 20 studies that were included in our analyses. We divided the studies into three groups according to the methods used to measure and analyze the association of breast density with alcohol consumption.

Results: Meta-analysis of the 11 studies that used quantitative methods to measure and analyze PBD as a continuous variable found a statistically significant difference in PBD when comparing the highest with the lowest alcohol level [β = 0.84; 95% confidence interval (CI), 0.12–1.56]. Three studies that used quantitative methods to measure PBD and categories of PBD for analysis had a summary OR = 1.81 (95% CI, 1.07–3.04). Five studies that used categories to classify PBD and analyze their association with alcohol intake had a summary OR = 1.78 (95% CI, 0.90–3.51).

Conclusions: These results suggest that there is a positive association between alcohol intake and PBD.

Impact: Alcohol may increase the risk of breast cancer associated with PBD. Cancer Epidemiol Biomarkers Prev; 26(2); 170–8. ©2016 AACR.
Data from Dietary Patterns and Plasma Sex Hormones, Prolactin, and Sex Hormone–Binding Globulin in Premenopausal Women
Authors: Hirko Kelly A. , Spiegelman Donna , Barnett Junaidah B. , Cho Eunyoung , Willett Walter C. , Hankinson Susan E. , Eliassen A. Heather
Published: April 2023

Abstract
Background: Sex hormones are important for breast cancer, but it is unclear whether dietary patterns influence hormone concentrations.

Methods: Dietary pattern adherence scores for the alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and Alternative Healthy Eating Index (AHEI) were calculated from semiquantitative food frequency questionnaires administered in 1995 and 1999. Premenopausal plasma concentrations of sex hormones were measured in samples collected in 1996 to 1999. We used generalized linear models to calculate geometric mean hormone concentrations across quartiles of dietary pattern scores among 1,990 women in the Nurses' Health Study II.

Results: We did not observe significant associations between sex hormone concentrations and the DASH pattern and only one suggestive association between follicular estrone concentrations and the aMED pattern [top vs. bottom quartile −4.4%, 95% confidence interval (CI), −10.6% to 2.1%; Ptrend = 0.06]. However, women in the top versus bottom quartile of AHEI score had lower concentrations of follicular (−9.1%; 95% CI, −16.1% to −1.4%; Ptrend = 0.04) and luteal (−7.5%; 95% CI, −13.6% to −0.9%; Ptrend = 0.01) estrone, luteal-free (−9.3%; 95% CI, −16.8% to −1.1%; Ptrend = 0.01) and total (−6.7 %; 95% CI, −14.3% to 1.5%; Ptrend = 0.04) estradiol, follicular estradiol (−14.2%; 95% CI, −24.6% to −2.4%; Ptrend = 0.05), and androstenedione (−7.8%; 95% CI, −15.4% to 0.4%; Ptrend = 0.03).

Conclusion: Diet quality measured by the AHEI is inversely associated with premenopausal estrogen concentrations. Given that we did not observe similar associations with the aMED or DASH patterns, our findings should be interpreted with caution.

Impact: Given the role of estrogens in breast cancer etiology, our findings add to the substantial evidence on the benefits of adhering to a healthy diet. Cancer Epidemiol Biomarkers Prev; 25(5); 791–8. ©2016 AACR.
Data from Differential Serum Cytokine Levels and Risk of Lung Cancer Between African and European Americans
Authors: Pine Sharon R. , Mechanic Leah E. , Enewold Lindsey , Bowman Elise D. , Ryan Bríd M. , Cote Michele L. , Wenzlaff Angela S. , Loffredo Christopher A. , Olivo-Marston Susan , Chaturvedi Anil , Caporaso Neil E. , Schwartz Ann G. , Harris Curtis C.
Published: April 2023

Abstract
Background: African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races.

Methods: Differences in 10 serum cytokine levels, IL1β, IL4, IL5, IL6, IL8, IL10, IL12, granulocyte macrophage colony-stimulating factor, IFNγ, and TNFα, between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case–control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the Wayne State University Karmanos Cancer Institute case–control study.

Results: Six cytokines, IL4, IL5, IL8, IL10, IFNγ, and TNFα, were significantly higher among European-American as compared with African-American controls. Elevated IL6 and IL8 levels were associated with lung cancer among both races in all three studies. Elevated IL1β, IL10, and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors.

Conclusions: Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans.

Impact: Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. Cancer Epidemiol Biomarkers Prev; 25(3); 488–97. ©2015 AACR.
Data from Is Pelvic Inflammatory Disease a Risk Factor for Ovarian Cancer?
Authors: Rasmussen Christina B. , Jensen Allan , Albieri Vanna , Andersen Klaus K. , Kjaer Susanne K.
Published: April 2023

Abstract
Background: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive, and only few cohort studies have been conducted.

Methods: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978–2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype.

Results: For ovarian cancer overall, we observed no association with PID (HR, 1.05; 95% CI, 0.92–1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR, 1.19; 1.00–1.41; P = 0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer.

Conclusions: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes.

Impact: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies. Cancer Epidemiol Biomarkers Prev; 26(1); 104–9. ©2016 AACR.
Data from The Effect of Change in Body Mass Index on Volumetric Measures of Mammographic Density
Authors: Hart Vicki , Reeves Katherine W. , Sturgeon Susan R. , Reich Nicholas G. , Sievert Lynnette Leidy , Kerlikowske Karla , Ma Lin , Shepherd John , Tice Jeffrey A. , Mahmoudzadeh Amir Pasha , Malkov Serghei , Sprague Brian L.
Published: April 2023

Abstract
Background: Understanding how changes in body mass index (BMI) relate to changes in mammographic density is necessary to evaluate adjustment for BMI gain/loss in studies of change in density and breast cancer risk. Increase in BMI has been associated with a decrease in percent density, but the effect on change in absolute dense area or volume is unclear.

Methods: We examined the association between change in BMI and change in volumetric breast density among 24,556 women in the San Francisco Mammography Registry from 2007 to 2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry measurements. Cross-sectional and longitudinal associations between BMI and dense volume (DV), non-dense volume (NDV), and percent dense volume (PDV) were assessed using multivariable linear regression models, adjusted for demographics, risk factors, and reproductive history.

Results: In cross-sectional analysis, BMI was positively associated with DV [β, 2.95 cm3; 95% confidence interval (CI), 2.69–3.21] and inversely associated with PDV (β, −2.03%; 95% CI, −2.09, −1.98). In contrast, increasing BMI was longitudinally associated with a decrease in both DV (β, −1.01 cm3; 95% CI, −1.59, −0.42) and PDV (β, −1.17%; 95% CI, −1.31, −1.04). These findings were consistent for both pre- and postmenopausal women.

Conclusion: Our findings support an inverse association between change in BMI and change in PDV. The association between increasing BMI and decreasing DV requires confirmation.

Impact: Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should evaluate adjustment for change in BMI. Cancer Epidemiol Biomarkers Prev; 24(11); 1724–30. ©2015 AACR.
Data from Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero
Authors: Hochstenbach Kevin , van Leeuwen Danitsja M. , Gmuender Hans , Gottschalk Ralf W. , Løvik Martinus , Granum Berit , Nygaard Unni , Namork Ellen , Kirsch-Volders Micheline , Decordier Ilse , Vande Loock Kim , Besselink Harrie , Törnqvist Margareta , von Stedingk Hans , Rydberg Per , Kleinjans Jos C.S. , van Loveren Henk , van Delft Joost H.M.
Published: April 2023

Abstract
Background: It has been suggested that fetal carcinogenic exposure might lead to predisposition to develop cancer during childhood or in later life possibly through modulation of the fetal transcriptome. Because gender effects in the incidence of childhood cancers have been described, we hypothesized differences at the transcriptomic level in cord blood between male and female newborns as a consequence of fetal carcinogenic exposure. The objective was to investigate whether transcriptomic responses to dietary genotoxic and nongenotoxic carcinogens show gender-specific mechanisms-of-action relevant for chemical carcinogenesis.

Methods: Global gene expression was applied in umbilical cord blood samples, the CALUX-assay was used for measuring dioxin(-like), androgen(-like), and estrogen(-like) internal exposure, and acrylamide–hemoglobin adduct levels were determined by mass spectrometry adduct-FIRE-procedureTM. To link gene expression to an established phenotypic biomarker of cancer risk, micronuclei frequencies were investigated.

Results: While exposure levels did not differ between sexes at birth, important gender-specific differences were observed in gene expressions associated with these exposures linked with cell cycle, the immune system and more general cellular processes such as posttranslation. Moreover, oppositely correlating leukemia/lymphoma genes between male and female newborns were identified in relation to the different biomarkers of exposure that might be relevant to male-specific predisposition to develop these cancers in childhood.

Conclusions/Impact: This study reveals different transcriptomic responses to environmental carcinogens between the sexes. In particular, male-specific TNF-alpha-NF-kB signaling upon dioxin exposure and activation of the Wnt-pathway in boys upon acrylamide exposure might represent possible mechanistic explanations for gender specificity in the incidence of childhood leukemia. Cancer Epidemiol Biomarkers Prev; 21(10); 1756–67. ©2012 AACR.
Data from Trends in Endometrial Cancer Incidence by Race and Histology with a Correction for the Prevalence of Hysterectomy, SEER 1992 to 2008
Authors: Jamison Patricia M. , Noone Anne-Michelle , Ries Lynn A.G. , Lee Nancy C. , Edwards Brenda K.
Published: April 2023

Abstract
Background: Incidence rates of endometrial cancer are routinely calculated without removing women who have had a hysterectomy from the denominator, which leads to an underestimate. Furthermore, as the number of women who have had a hysterectomy (hysterectomy prevalence) varies by race, the estimate of racial difference in endometrial cancer incidence is incorrect.

Methods: Data from 1992 to 2008 from the SEER Program were used to calculate incidence rates of endometrial cancer (corpus uterus and uterus, NOS) for 67,588 women 50 years and older. Data from the Behavioral Risk Factor Surveillance System were used to estimate hysterectomy prevalence. SEER area populations were reduced by hysterectomy prevalence, and corrected incidence rates were calculated.

Results: For women 50 years and older, the corrected incidence rate of endometrial cancer was 136.0 per 100,000 among whites and 115.5 among blacks, a 73% and 90% increase respectively compared with the uncorrected rate. The increase was greater for black women because hysterectomy prevalence was higher among black women (47%) than white women (41%). The corrected incidence among black women significantly increased 3.1% per year compared with a 0.8% significant decrease among white women resulting in higher rates among black women toward the end of the study period.

Conclusion: Correcting the incidence rate for hysterectomy prevalence provides more accurate estimates of endometrial cancer risk over time.

Impact: Comparisons of rates of endometrial cancer among racial groups may be misleading in the absence of denominator correction for hysterectomy prevalence. Cancer Epidemiol Biomarkers Prev; 22(2); 233–41. ©2012 AACR.
Data from Collecting Fecal Samples for Microbiome Analyses in Epidemiology Studies
Authors: Sinha Rashmi , Chen Jun , Amir Amnon , Vogtmann Emily , Shi Jianxin , Inman Kristin S. , Flores Roberto , Sampson Joshua , Knight Rob , Chia Nicholas
Published: April 2023

Abstract
Background: The need to develop valid methods for sampling and analyzing fecal specimens for microbiome studies is increasingly important, especially for large population studies.

Methods: Some of the most important attributes of any sampling method are reproducibility, stability, and accuracy. We compared seven fecal sampling methods [no additive, RNAlater, 70% ethanol, EDTA, dry swab, and pre/post development fecal occult blood test (FOBT)] using 16S rRNA microbiome profiling in two laboratories. We evaluated nine commonly used microbiome metrics: abundance of three phyla, two alpha-diversities, and four beta-diversities. We determined the technical reproducibility, stability at ambient temperature, and accuracy.

Results: Although microbiome profiles showed systematic biases according to sample method and time at ambient temperature, the highest source of variation was between individuals. All collection methods showed high reproducibility. FOBT and RNAlater resulted in the highest stability without freezing for 4 days. In comparison with no-additive samples, swab, FOBT, and 70% ethanol exhibited the greatest accuracy when immediately frozen.

Conclusions: Overall, optimal stability and reproducibility were achieved using FOBT, making this a reasonable sample collection method for 16S analysis.

Impact: Having standardized method of collecting and storing stable fecal samples will allow future investigations into the role of gut microbiota in chronic disease etiology in large population studies. Cancer Epidemiol Biomarkers Prev; 25(2); 407–16. ©2015 AACR.