bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from An Exploration of Changes in the Measurement of Mammography in the National Health Interview Survey
Authors: Gonzales Felisa A. , Willis Gordon B. , Breen Nancy , Yan Ting , Cronin Kathy A. , Taplin Stephen H. , Yu Mandi
Published: April 2023

Abstract
Background: Using the National Health Interview Survey (NHIS), we examined the effect of question wording on estimates of past-year mammography among racially/ethnically diverse women ages 40–49 and 50–74 without a history of breast cancer.

Methods: Data from one-part (“Have you had a mammogram during the past 12 months?”) and two-part (“Have you ever had a mammogram”; “When did you have your most recent mammogram?”) mammography history questions administered in the 2008, 2011, and 2013 NHIS were analyzed. χ2 tests provided estimates of changes in mammography when question wording was either the same (two-part question) or differed (two-part question followed by one-part question) in the two survey years compared. Crosstabulations and regression models assessed the type, extent, and correlates of inconsistent responses to the two questions in 2013.

Results: Reports of past-year mammography were slightly higher in years when the one-part question was asked than when the two-part question was asked. Nearly 10% of women provided inconsistent responses to the two questions asked in 2013. Black women ages 50 to 74 [adjusted OR (aOR), 1.50; 95% confidence interval (CI), 1.16–1.93] and women ages 40–49 in poor health (aOR, 2.22; 95% CI, 1.09–4.52) had higher odds of inconsistent responses; women without a usual source of care had lower odds (40–49: aOR, 0.42; 95% CI, 0.21–0.85; 50–74: aOR, 0.42; 95% CI, 0.24–0.74).

Conclusions: Self-reports of mammography are sensitive to question wording. Researchers should use equivalent questions that have been designed to minimize response biases such as telescoping and social desirability.

Impact: Trend analyses relying on differently worded questions may be misleading and conceal disparities. Cancer Epidemiol Biomarkers Prev; 26(11); 1611–8. ©2017 AACR.
Data from Genetic Predictors of Circulating 25-Hydroxyvitamin D and Risk of Colorectal Cancer
Authors: Hiraki Linda T. , Qu Conghui , Hutter Carolyn M. , Baron John A. , Berndt Sonja I. , Bézieau Stéphane , Brenner Hermann , Caan Bette J. , Casey Graham , Chang-Claude Jenny , Chanock Stephen J. , Conti David V. , Duggan David , Fuchs Charles S. , Gallinger Steven , Giovannucci Edward L. , Harrison Tabitha A. , Hayes Richard B. , Hazra Aditi , Henderson Brian , Hoffmeister Michael , Hopper John L. , Hudson Thomas J. , Jenkins Mark A. , Küry Sébastien , Le Marchand Loic , Lemire Mathieu , Ma Jing , Manson JoAnn E. , Nan Hongmei , Newcomb Polly A. , Ng Kimmie , Potter John D. , Schoen Robert E. , Schumacher Fredrick R. , Seminara Daniela , Slattery Martha L. , Wactawski-Wende Jean , White Emily , Wu Kana , Zanke Brent W. , Kraft Peter , Peters Ulrike , Chan Andrew T.
Published: April 2023

Abstract
Background: Experimental evidence has demonstrated an antineoplastic role for vitamin D in the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D.

Methods: We investigated whether five polymorphisms in GC, CYP2R1, CYP24A1, and DHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate-adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS).

Results: We did not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately.

Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25(OH)D and colorectal cancer risk.

Impact: There was no association observed between genetic markers of circulating 25(OH)D and colorectal cancer. These genetic markers account for a small proportion of the variance in 25(OH)D. Cancer Epidemiol Biomarkers Prev; 22(11); 2037–46. ©2013 AACR.
Data from Targetome Profiling, Pathway Analysis and Genetic Association Study Implicate miR-202 in Lymphomagenesis
Authors: Hoffman Aaron E. , Liu Ran , Fu Alan , Zheng Tongzhang , Slack Frank , Zhu Yong
Published: April 2023

Abstract
Background: miRNAs have been implicated in numerous tumorigenic pathways, and previous studies have associated miR-202 dysregulation with various cancer types, including follicular lymphoma.

Methods: The miR-202 targetome was identified by ribonucleoprotein immunoprecipitation-microarray (RIP-Chip), and functional interactions among identified targets were investigated using the Ingenuity Pathway Analysis tool. We also conducted a population-based genetic association study of a polymorphism within the miR-202 stem-loop sequence and risk of non-Hodgkin lymphoma. In vitro gain-of-function experiments were further conducted to elucidate the functional significance of the variant.

Results: A total of 141 potential members of the miR-202 targetome were identified by a transcriptome-wide RIP-Chip assay. Functional interactions among identified targets suggested that miR-202-regulated genes are involved in biologic pathways relevant for hematologic function and cancer. Consistent with this, a genetic association analysis using human blood samples revealed a significant association between a germline mutation (rs12355840) in the miR-202 precursor sequence and follicular lymphoma risk. An in vitro functional assay further showed that the variant allele resulted in diminished miR-202 levels, possibly by altering precursor-processing efficiency.

Conclusions: Taken together, our findings suggest that miR-202 is involved in follicular lymphomagenesis.

Impact: These findings implicate miR-202 as a potential tumor suppressor in follicular lymphoma and warrant the investigation of miR-202 as a novel biomarker of follicular lymphoma risk. Cancer Epidemiol Biomarkers Prev; 22(3); 327–36. ©2013 AACR.
Data from Associations between 25 Lung Cancer Risk–Related SNPs and Polycyclic Aromatic Hydrocarbon–Induced Genetic Damage in Coke Oven Workers
Authors: Dai Xiayun , Deng Siyun , Wang Tian , Qiu Gaokun , Li Jun , Yang Binyao , Feng Wei , He Xiaosheng , Deng Qifei , Ye Jian , Zhang Wangzhen , He Meian , Zhang Xiaomin , Guo Huan , Wu Tangchun
Published: April 2023

Abstract
Background: Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. However, whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH).

Methods: We cross-sectionally investigated the associations between SNPs from published GWAS for lung cancer in Asians and PAH-induced genetic damage in 1,557 coke oven workers in China. Urinary PAH metabolites, plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei (MN) frequency were determined by gas chromatography-mass spectrometry, sandwich ELISA, high-performance liquid chromatography, and cytokinesis-block micronucleus assay, respectively.

Results: 13q12.12-rs753955C was suggestively associated with elevated 8-OHdG levels (P = 0.003). Higher 8-OHdG levels were observed in individuals with rare allele homozygotes (CC) than in TT homozygotes (β, 0.297; 95% confidence interval, 0.124–0.471; P = 0.001). 9p21-rs1333040C, 10p14-rs1663689G, and 15q25.1-rs3813572G were significantly associated with lower MN frequency (P values were 0.002, 0.001, and 0.005, respectively). 10p14-rs1663689G polymorphism downregulated the relationship of the total concentration of PAH metabolites to 8-OHdG levels (Pinteraction = 0.002). TERT-rs2736100G and VTI1A-rs7086803A aggravated the relationship of BPDE-Alb adducts to MN frequency, whereas BPTF-rs7216064G attenuated that correlation (all Pinteraction < 0.001).

Conclusions: Lung cancer risk–associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency.

Impact: Lung cancer risk–associated SNPs might influence one's susceptibility to genetic damage caused by PAHs. Cancer Epidemiol Biomarkers Prev; 23(6); 986–96. ©2014 AACR.
Data from Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk
Authors: Thrift Aaron P. , Gong Jian , Peters Ulrike , Chang-Claude Jenny , Rudolph Anja , Slattery Martha L. , Chan Andrew T. , Locke Adam E. , Kahali Bratati , Justice Anne E. , Pers Tune H. , Gallinger Steven , Hayes Richard B. , Baron John A. , Caan Bette J. , Ogino Shuji , Berndt Sonja I. , Chanock Stephen J. , Casey Graham , Haile Robert W. , Du Mengmeng , Harrison Tabitha A. , Thornquist Mark , Duggan David J. , Le Marchand Loïc , Lindor Noralane M. , Seminara Daniela , Song Mingyang , Wu Kana , Thibodeau Stephen N. , Cotterchio Michelle , Win Aung Ko , Jenkins Mark A. , Hopper John L. , Ulrich Cornelia M. , Potter John D. , Newcomb Polly A. , Hoffmeister Michael , Brenner Hermann , White Emily , Hsu Li , Campbell Peter T.
Published: April 2023

Abstract
Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer.

Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis.

Results: Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10–1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m2, 1.50; 95% CI, 1.13–2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m2, 1.82; 95% CI, 1.26–2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 1.18; 95% CI, 0.73–1.92).

Conclusions: High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation.

Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(7); 1024–31. ©2015 AACR.
Data from Tissue Biomarkers for Prognosis of Prostate Cancer: A Systematic Review and Meta-analysis
Authors: Zhao Liuyang , Yu Na , Guo Tianfang , Hou Yixuan , Zeng Zongyue , Yang Xiaorong , Hu Ping , Tang Xi , Wang Jian , Liu Manran
Published: April 2023

Abstract
Background: Although numerous investigators have made efforts to assess prognostic biomarkers of prostate cancer, no biomarker has been recommended for clinical practice.

Methods: According to REMARK (Reporting recommendations for tumor marker prognostic studies) and MISFISHIE (Minimum information specification for in situ hybridization and immunohistochemistry experiments) guidelines, the published articles of immunohistochemistry-based prognostic biomarkers on prostate cancer were extracted and pooled.

Results: Ninety-three prognostic biomarkers from 92 high-quality cohort studies were included in this meta-analysis. Our analysis reveals some promising independent prognostic biomarkers, including Ki-67 [all-cause mortality (ACM) HR, 1.85; 95% confidence interval (CI), 1.06–3.25; PSM HR, 1.82; 95% CI, 1.42–2.34; DFS HR, 1.51; 95% CI, 1.31–1.75]; Bcl-2 (ACM HR, 2.14; 95% CI, 1.27–3.58; PSM HR, 1.61; 95% CI, 1.01–2.57; DFS HR, 3.86; 95% CI, 2.14–6.96); CD147 (ACM HR, 2.63; 95% CI, 1.19–5.81; DFS HR, 5.84; 95% CI, 3.41–9.99); COX-2 (PSM HR, 7.6; 95% CI, 0.7–80.1; DFS HR, 7.9; 95% CI, 2.62–23.83); ALDH1A1 (ACM HR, 1.73; 95% CI, 1.163–2.527; PSM HR, 1.05; 95% CI, 1.028–1.107), and FVIII (ACM HR, 1.76; 95% CI, 1.19–2.60; PSM HR, 1.01; 95% CI, 1.01–1.02).

Conclusions: Our analysis identified a subset of biomarkers (Ki-67, Bcl-2, CD147, COX-2, ALDH1A1, and FVIII) that may have prognostic value for predicting the outcome of patients with prostate cancer.

Impact: These reliable prognostic biomarkers will improve the clinical management of patients with prostate cancer. Cancer Epidemiol Biomarkers Prev; 23(6); 1047–54. ©2014 AACR.
Data from Alcohol Drinking and Second Primary Cancer Risk in Patients with Upper Aerodigestive Tract Cancers: A Systematic Review and Meta-analysis of Observational Studies
Authors: Druesne-Pecollo Nathalie , Keita Youssouf , Touvier Mathilde , Chan Doris S.M. , Norat Teresa , Hercberg Serge , Latino-Martel Paule
Published: April 2023

Abstract
Background: We conducted a systematic review and meta-analysis of existing data from observational studies to assess the strength of the association of alcohol drinking with second primary cancer risk in patients with upper aerodigestive tract (UADT; oral cavity, pharynx, larynx, and esophagus) cancer.

Methods: PubMed and Embase were searched up to July 2012 and the reference lists of studies included in the analysis were examined. Random-effects models were used to estimate summary relative risks (RR) and 95% confidence interval (CI).

Results: Nineteen studies, 8 cohort and 11 case–control studies, were included. In highest versus lowest meta-analyses, alcohol drinking was associated with significantly increased risk of UADT second primary cancers (RR, 2.97; 95% CI, 1.96–4.50). Significantly increased risks were also observed for UADT and lung combined (RR, 1.90; 95% CI, 1.16–3.11) and all sites (RR, 1.60; 95% CI, 1.22–2.10) second primary cancers. For an increase in the alcohol intake of 10 grams per day, dose–response meta-analysis resulted in a significantly increased RR of 1.09 (95% CI, 1.04–1.14) for UADT second primary cancers.

Conclusions: Alcohol drinking in patients with UADT cancer is associated with an increased risk of second primary cancers. Studies conducted in alcohol drinking patients with UADT cancer and evaluating the effect of alcohol cessation on second primary cancer and other outcomes are needed.

Impact: Our results emphasize the importance of prevention policies aiming to reduce alcohol drinking. Health-care professionals should encourage alcohol drinking patients with UADT cancer to reduce their consumption and reinforce the surveillance of this at-risk subpopulation. Cancer Epidemiol Biomarkers Prev; 23(2); 324–31. ©2013 AACR.
Data from Biomarkers of Tobacco Exposure: Summary of an FDA-Sponsored Public Workshop
Authors: Chang Cindy M. , Edwards Selvin H. , Arab Aarthi , Del Valle-Pinero Arseima Y. , Yang Ling , Hatsukami Dorothy K.
Published: April 2023

Abstract
Since 2009, the FDA Center for Tobacco Products (CTP) has had the authority to regulate the manufacturing, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers of exposure pertain to actual human exposure to chemicals arising from tobacco use and could play an important role across a number of FDA regulatory activities, including assessing new and modified-risk tobacco products and identifying and evaluating potential product standards. On August 3–4, 2015, FDA/CTP hosted a public workshop focused on biomarkers of exposure with participants from government, industry, academia, and other organizations. The workshop was divided into four sessions focused on: (i) approaches to evaluating and selecting biomarkers; (ii) biomarkers of exposure and relationship to disease risk; (iii) currently used biomarkers of exposure and biomarkers in development; and (iv) biomarkers of exposure and the assessment of smokeless tobacco and electronic nicotine delivery systems. This article synthesizes the main findings from the workshop and highlights research areas that could further strengthen the science around biomarkers of exposure and help determine their application in tobacco product regulation. Cancer Epidemiol Biomarkers Prev; 26(3); 291–302. ©2016 AACR.
Data from The Natural History of Cervical Cancer in Chinese Women: Results from an 11-Year Follow-Up Study in China Using a Multistate Model
Authors: Zhang Shao-Kai , Kang Le-Ni , Chang Irene J. , Zhao Fang-Hui , Hu Shang-Ying , Chen Wen , Shi Ju-Fang , Zhang Xun , Pan Qin-Jing , Li Shu-Min , Qiao You-Lin
Published: April 2023

Abstract
Background: It is important to understand the natural history of cervical cancer, which has implications for cancer prevention and management. However, a dearth of studies on the long-term development of cervical cancer exists in China.

Methods: We investigated the natural history of cervical cancer in Chinese women by creating a multistate model using 11 years of follow-up data from the Shanxi Province Cervical Cancer Screening Study I conducted from 1999 to 2010. In 1999, a total of 1,997 eligible women, ages 35 to 45 years, were enrolled in Xiangyuan County, Shanxi Province. Participants were followed up in 2005 and 2010, respectively.

Results: The average time a subject spent in CIN1 before transiting into another state was 1.4693 years [95% confidence interval (CI): 1.1215–1.9251] and the average time a subject spent in CIN2 was 2.9822 years (95% CI: 1.9790–4.4938). A subject's transition probability from CIN1 to normal increased with time. However, the transition probability from CIN1 to CIN2 was relatively lower, with 3-, 5-, and 10-year transition probabilities of 0.1415, 0.1066, and 0.0437. Comparison of 5-year transition probabilities between CIN2 to normal/CIN1 and CIN2 to CIN3+ yielded a ratio of 2.74.

Conclusions: Women with CIN1 had a substantial tendency for regression. Similarly, women with CIN2 had a higher probability of regression to normal/CIN1 than progression to CIN3+. Findings in this study may have significant implications for the development and evaluation of formal cervical cancer preventive strategies in China.

Impact: This study may serve as a valuable reference to future research on other multistate cancer processes. Cancer Epidemiol Biomarkers Prev; 23(7); 1298–305. ©2014 AACR.
Data from Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma
Authors: Zhang Weikang , Liu Hongliang , Liu Zhensheng , Zhu Dakai , Amos Christopher I. , Fang Shenying , Lee Jeffrey E. , Wei Qingyi
Published: April 2023

Abstract
Background: The Notch signaling pathway is constitutively activated in human cutaneous melanoma to promote growth and aggressive metastatic potential of primary melanoma cells. Therefore, genetic variants in Notch pathway genes may affect the prognosis of cutaneous melanoma patients.

Methods: We identified 6,256 SNPs in 48 Notch genes in 858 cutaneous melanoma patients included in a previously published cutaneous melanoma genome-wide association study dataset. Multivariate and stepwise Cox proportional hazards regression and false-positive report probability corrections were performed to evaluate associations between putative functional SNPs and cutaneous melanoma disease-specific survival. Receiver operating characteristic curve was constructed, and area under the curve was used to assess the classification performance of the model.

Results: Four putative functional SNPs of Notch pathway genes had independent and joint predictive roles in survival of cutaneous melanoma patients. The most significant variant was NCOR2 rs2342924 T>C (adjusted HR, 2.71; 95% confidence interval, 1.73–4.23; Ptrend = 9.62 × 10−7), followed by NCSTN rs1124379 G>A, NCOR2 rs10846684 G>A, and MAML2 rs7953425 G>A (Ptrend = 0.005, 0.005, and 0.013, respectively). The receiver operating characteristic analysis revealed that area under the curve was significantly increased after adding the combined unfavorable genotype score to the model containing the known clinicopathologic factors.

Conclusions: Our results suggest that SNPs in Notch pathway genes may be predictors of cutaneous melanoma disease-specific survival.

Impact: Our discovery offers a translational potential for using genetic variants in Notch pathway genes as a genotype score of biomarkers for developing an improved prognostic assessment and personalized management of cutaneous melanoma patients. Cancer Epidemiol Biomarkers Prev; 24(7); 1101–10. ©2015 AACR.
Data from A Newly Identified Susceptibility Locus near FOXP1 Modifies the Association of Gastroesophageal Reflux with Barrett's Esophagus
Authors: Dai James Y. , de Dieu Tapsoba Jean , Buas Matthew F. , Onstad Lynn E. , Levine David M. , Risch Harvey A. , Chow Wong-Ho , Bernstein Leslie , Ye Weimin , Lagergren Jesper , Bird Nigel C. , Corley Douglas A. , Shaheen Nicholas J. , Wu Anna H. , Reid Brian J. , Hardie Laura J. , Whiteman David C. , Vaughan Thomas L.
Published: April 2023

Abstract
Background: Important risk factors for esophageal adenocarcinoma and its precursor, Barrett's esophagus, include gastroesophageal reflux disease, obesity, and cigarette smoking. Recently, genome-wide association studies have identified seven germline single-nucleotide polymorphisms (SNP) that are associated with risk of Barrett's esophagus and esophageal adenocarcinoma. Whether these genetic susceptibility loci modify previously identified exposure–disease associations is unclear.

Methods: We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1,516 esophageal adenocarcinoma case patients, 2,416 Barrett's esophagus case patients, and 2,187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate ORs for these risk factors stratified by SNP genotype, separately for Barrett's esophagus and esophageal adenocarcinoma.

Results: The odds ratio for Barrett's esophagus associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of rs2687201 (nominal P = 0.0005, FDR = 0.042). ORs (95% CIs) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of rs2687201 were 6.17 (4.91–7.56), 3.56 (2.85–4.44), and 3.97 (2.47–6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index.

Conclusion: Reflux symptoms are more strongly associated with Barrett's esophagus risk among persons homozygous for the major allele of rs2687201, which lies approximately 75 kb downstream of the transcription factor gene FOXP1.

Impact: The novel gene–exposure interaction discovered in this study provides new insights into the etiology of esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 24(11); 1739–47. ©2015 AACR.
Data from Genetic Polymorphisms in Inflammation Pathway Genes and Prostate Cancer Risk
Authors: Kwon Erika M. , Salinas Claudia A. , Kolb Suzanne , Fu Rong , Feng Ziding , Stanford Janet L. , Ostrander Elaine A.
Published: April 2023

Abstract
Background: Chronic inflammation is an important mechanism for the development and progression of prostate cancer (PC). To better understand the potential relationship between genes in the inflammation pathway and PC risk, we evaluated variants in 16 candidate genes.

Methods: A total of 143 tagging and amino acid altering single nucleotide polymorphisms (SNPs) were genotyped in Caucasian and African American men participating in one of two population-based, case–control studies (n = 1,458 cases and 1,351 controls). The relative risk of PC was estimated using logistic and polytomous regression models.

Results: Ten SNPs in seven genes (CXCL12, IL4, IL6, IL6ST, PTGS2, STAT3, and TNF) were nominally associated (P < 0.05) with risk of PC in Caucasians. The most significant effect on risk was seen with rs11574783 in the interleukin 6 signal transducer (IL6ST) gene (OR = 0.08, 95% CI: 0.01–0.63). Cumulatively, four SNPs in genes interleukin 4 (IL4), IL6ST, PTGS2, and signal transducer and activator of transcription 3 (STAT3) conferred a three-fold elevation in PC risk among men carrying the maximum number of high-risk alleles (OR = 2.97, 95% CI: 1.41–6.25, Ptrend = 0.0003). Risk estimates for seven SNPs varied significantly according to disease aggressiveness (Phomogeneity < 0.05), with SNPs in AKT1, PIK3R1, and STAT3 independently associated with more aggressive PC; OR = 5.1 (95% CI: 2.29–11.40, Ptrend = 3.8 × 10−5) for carriers of all high-risk genotypes.

Conclusions: These results suggest that variants in genes within the inflammation pathway may play a role in the development of PC, however, further studies are needed to replicate our findings.

Impact: These results underline the potential importance of the inflammation pathway in PC development and progression. Cancer Epidemiol Biomarkers Prev; 20(5); 923–33. ©2011 AACR.
Data from RAZOR: A Phase II Open Randomized Trial of Screening Plus Goserelin and Raloxifene Versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer
Authors: Howell Anthony , Ashcroft Linda , Fallowfield Lesley , Eccles Diana M. , Eeles Rosalind A. , Ward Ann , Brentnall Adam R. , Dowsett Mitchell , Cuzick Jack M. , Greenhalgh Rosemary , Boggis Caroline , Motion Jamie , Sergeant Jamie C. , Adams Judith , Evans D. Gareth
Published: April 2023

Abstract
Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention.

Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density.

Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period.

Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed.

Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58–66. ©2017 AACR.
Data from Genome-Wide Association Study Identifies Possible Genetic Risk Factors for Colorectal Adenomas
Authors: Edwards Todd L. , Shrubsole Martha J. , Cai Qiuyin , Li Guoliang , Dai Qi , Rex Douglas K. , Ulbright Thomas M. , Fu Zhenming , Delahanty Ryan H. , Murff Harvey J. , Smalley Walter , Ness Reid M. , Zheng Wei
Published: April 2023

Abstract
Background: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown.

Methods: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis.

Results: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81–0.94; P = 4.4 × 10−4), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18–1.47; P = 1.1 × 10−6).

Conclusions: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies.

Impact: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(7); 1219–26. ©2013 AACR.
Data from Circulating Long RNAs in Serum Extracellular Vesicles: Their Characterization and Potential Application as Biomarkers for Diagnosis of Colorectal Cancer
Authors: Dong Lei , Lin Wanrun , Qi Peng , Xu Mi-die , Wu Xiaoben , Ni Shujuan , Huang Dan , Weng Wei-wei , Tan Cong , Sheng Weiqi , Zhou Xiaoyan , Du Xiang
Published: April 2023

Abstract
Background: Long noncoding RNA (lncRNA) and mRNAs are long RNAs (≥200 nucleotides) compared with miRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (AB), microvesicles (MV), and exosomes (EXO). They are potential biomarkers for identifying cancer.

Methods: Sera from 76 preoperative colorectal cancer patients, 76 age- and sex-matched healthy subjects, and 20 colorectal adenoma patients without colorectal cancer were collected. We investigated the distribution of long RNAs into the three vesicles. Seventy-nine cancer-related long RNAs were chosen and detected using qPCR.

Results: The quantity of long RNA has varying distribution among three subtypes of extracellular vesicles in serum. Most mRNA and lncRNA genes had higher quantity in EXOs than that in ABs and MVs, whereas MVs contain lowest quantity. We investigated 79 long RNAs chosen from The Cancer Genome Atlas and the LncRNADisease database in the sera of healthy patients, and those with colorectal cancer. In the training and test sets, the AUCs were 0.936 and 0.877, respectively. The AUC of total serum RNA was lower (0.857) than that of exosomal RNA in the same samples (0.936).

Conclusion: The present study shows that exosomal mRNAs and lncRNAs in serum could be used as biomarkers to detect colorectal cancer.

Impact: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured long RNAs. The combination of two mRNAs, KRTAP5-4 and MAGEA3, and one lncRNA, BCAR4, could be potential candidates to detect colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1158–66. ©2016 AACR.
Data from An Exploratory Study of Respiratory Quotient Calibration and Association with Postmenopausal Breast Cancer
Authors: Prentice Ross L. , Neuhouser Marian L. , Tinker Lesley F. , Pettinger Mary , Thomson Cynthia A. , Mossavar-Rahmani Yasmin , Thomas Fridtjof , Qi Lihong , Huang Ying
Published: April 2023

Abstract
Background: The respiratory quotient (RQ), defined as the ratio of carbon dioxide exhaled to oxygen uptake, reflects substrate utilization when energy is expended. Fat and alcohol have RQ values of approximately 0.7, compared with 1.0 for carbohydrate, and approximately 0.8 for protein. Here, the association between RQ and postmenopausal breast cancer risk is studied.

Methods: Paired RQ measurements were obtained, separated by approximately 6 months, for women in the reliability subset of a Women's Health Initiative (WHI) Nutrition and Physical Activity Assessment Study. Linear regression of the average of the paired log RQ assessments on a corresponding log food quotient (FQ) average and other study subject characteristics, including age, body mass index, race, and education, yielded calibration equations for predicting RQ.

Results: Calibration equations, using any of food frequency, food record, or dietary recall data, explained an appreciable fraction of measured log RQ variation, and these were used to compute calibrated RQ estimates throughout WHI cohorts. Calibrated RQ estimates using 4-day food record (4DFR) data related inversely (P = 0.004) to (invasive) breast cancer risk in the WHI Dietary Modification trial comparison group, and corresponding RQ estimates using food-frequency data related inversely (P = 0.002) to breast cancer incidence in this cohort combined with the larger WHI observational study.

Conclusion: Although preliminary, these analyses suggest a substantially higher postmenopausal breast cancer risk among women having relatively low RQ.

Impact: RQ elevation could provide a novel target for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev; 22(12); 2374–83. ©2013 AACR.
Data from Cholesterol Levels in Blood and the Risk of Prostate Cancer: A Meta-analysis of 14 Prospective Studies
Authors: YuPeng Liu , YuXue Zhang , PengFei Li , Cheng Cheng , YaShuang Zhao , DaPeng Li , Chen Du
Published: April 2023

Abstract
Background: As a neutral lipid and prominent component of the Western diet, cholesterol levels might be a risk factor for prostate cancer. However, current evidence has been inconsistent. This meta-analysis aimed to evaluate the association between blood cholesterol levels and the risk of prostate cancer.

Methods: An extensive search was performed in MEDLINE and EMBASE for prospective studies that have reported the association between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) levels in blood and risk of prostate cancer. Random-effects models were used to summarize the study-specific results.

Results: Fourteen studies were included in this meta-analysis. In the meta-analysis, the summarized risk ratios (RR) for the highest to lowest cholesterol levels were as follows: 1.05 [95% confidence interval (CI), 0.97–1.14; P = 0.21] for TC, 0.93 (95% CI, 0.80–1.10; P = 0.40) for HDL, and 1.17 (95% CI, 0.88–1.55; P = 0.51) for LDL. When restricting to high-grade prostate cancer, the pooled RR was 1.32 (95% CI, 0.93–1.87; P = 0.13) for TC. In dose–response analyses, a 1 mmol/L increment in blood TC, HDL, and LDL level conferred an RR of 1.01 (95% CI, 0.99–1.02; P = 0.38), 0.98 (95% CI, 0.91–1.07; P = 0.72), and 1.04 (95% CI, 0.98–1.10; P = 0.24), respectively.

Conclusion: In this meta-analysis of 14 large prospective studies, blood TC, HDL, and LDL levels were not associated with the risk of either overall prostate cancer or high-grade prostate cancer.

Impact: Our findings did not appear to support the hypothesis that hypercholesterolemia increases the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(7); 1086–93. ©2015 AACR.
Data from Secondhand Tobacco Smoke Exposure and Lung Adenocarcinoma In Situ/Minimally Invasive Adenocarcinoma (AIS/MIA)
Authors: Kim Claire H. , Lee Yuan-Chin Amy , Hung Rayjean J. , Boffetta Paolo , Xie Dong , Wampfler Jason A. , Cote Michele L. , Chang Shen-Chih , Ugolini Donatella , Neri Monica , Le Marchand Loic , Schwartz Ann G. , Morgenstern Hal , Christiani David C. , Yang Ping , Zhang Zuo-Feng
Published: April 2023

Abstract
The aim of this study was to estimate the effect of exposure to secondhand tobacco smoke on the incidence of lung adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA). Data from seven case–control studies participating in the International Lung Cancer Consortium (ILCCO) were pooled, resulting in 625 cases of AIS/MIA and 7,403 controls, of whom 170 cases and 3,035 controls were never smokers. Unconditional logistic regression was used to estimate adjusted ORs (ORadj) and 95% confidence intervals (CI), controlling for age, sex, race, smoking status (ever/never), and pack-years of smoking. Study center was included in the models as a random-effects intercept term. Ever versus never exposure to secondhand tobacco smoke was positively associated with AIS/MIA incidence in all subjects (ORadj = 1.48; 95% CI, 1.14–1.93) and in never smokers (ORadj = 1.45; 95% CI, 1.00–2.12). There was, however, appreciable heterogeneity of ORadj across studies (P = 0.01), and the pooled estimates were largely influenced by one large study (40% of all cases and 30% of all controls). These findings provide weak evidence for an effect of secondhand tobacco smoke exposure on AIS/MIA incidence. Further studies are needed to assess the impact of secondhand tobacco smoke exposure using the newly recommended classification of subtypes of lung adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 24(12); 1902–6. ©2015 AACR.
Data from Genetic Variants in Immune-Related Pathways and Breast Cancer Risk in African American Women in the AMBER Consortium
Authors: Hong Chi-Chen , Sucheston-Campbell Lara E. , Liu Song , Hu Qiang , Yao Song , Lunetta Kathryn L. , Haddad Stephen A. , Ruiz-Narváez Edward A. , Bensen Jeannette T. , Cheng Ting-Yuan David , Bandera Elisa V. , Rosenberg Lynn A. , Haiman Christopher A. , Lee Kelvin , Evans Sharon S. , Abrams Scott I. , Repasky Elizabeth A. , Olshan Andrew F. , Palmer Julie R. , Ambrosone Christine B.
Published: April 2023

Abstract
Background: Constitutional immunity shaped by exposure to endemic infectious diseases and parasitic worms in Sub-Saharan Africa may play a role in the etiology of breast cancer among African American (AA) women.

Methods: A total of 149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based pathway analyses were conducted using the adaptive rank truncated product statistic for overall breast cancer risk, and risk by estrogen receptor (ER) status. Unconditional logistic regression analysis was used to estimate ORs and 95% confidence intervals (CIs) for single variants.

Results: The top pathways were Interleukin binding (P = 0.01), Biocarta TNFR2 (P = 0.005), and positive regulation of cytokine production (P = 0.024) for overall, ER+, and ER− cancers, respectively. The most significant gene was IL2RB (P = 0.001) for overall cancer, with rs228952 being the top variant identified (OR = 0.85; 95% CI, 0.79–0.92). Only BCL3 contained a significant variant for ER+ breast cancer. Variants in IL2RB, TLR6, IL8, PRKDC, and MAP3K1 were associated with ER− disease. The only genes showing heterogeneity between ER− and ER+ cancers were TRAF1, MAP3K1, and MAPK3 (P ≤ 0.02). We also noted genes associated with autoimmune and atopic disorders.

Conclusions: Findings from this study suggest that genetic variants in immune pathways are relevant to breast cancer susceptibility among AA women, both for ER+ and ER− breast cancers.

Impact: Results from this study extend our understanding of how inherited genetic variation in immune pathways is relevant to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 27(3); 321–30. ©2018 AACR.
Data from Identification of Breast Cancer DNA Methylation Markers Optimized for Fine-Needle Aspiration Samples
Authors: Bu Dawei , Lewis Cheryl M. , Sarode Venetia , Chen Min , Ma Xiaotu , Lazorwitz Aaron M. , Rao Roshni , Leitch Marilyn , Moldrem Amy , Andrews Valerie , Gazdar Adi , Euhus David
Published: April 2023

Abstract
Background: Random periareolar fine-needle aspiration (RP-FNA) is increasingly used in trials of breast cancer prevention for biomarker assessments. DNA methylation markers may have value as surrogate endpoint biomarkers, but this requires identification of biologically relevant markers suitable for paucicellular, lymphocyte-contaminated clinical samples.

Methods: Unbiased whole-genome 5-aza-2′-deoxycytidine (5AZA)–induced gene expression assays, followed by several phases of qualitative and quantitative methylation-specific PCR (MSP) testing, were used to identify novel breast cancer DNA methylation markers optimized for clinical FNA samples.

Results: The initial 5AZA experiment identified 453 genes whose expression was potentially regulated by promoter region methylation. Informatics filters excluded 273 genes unlikely to yield useful DNA methylation markers. MSP assays were designed for 271 of the remaining genes and, ultimately, 33 genes were identified that were differentially methylated in clinical breast cancer samples, as compared with benign RP-FNA samples, and never methylated in lymphocytes. A subset of these markers was validated by quantitative multiplex MSP in extended clinical sample sets. Using a novel permutation method for analysis of quantitative methylation data, PSAT1, GNE, CPNE8, and CXCL14 were found to correlate strongly with specific clinical and pathologic features of breast cancer. In general, our approach identified markers methylated in a smaller subpopulation of tumor cells than those identified in published methylation array studies.

Conclusions: Clinically relevant DNA methylation markers were identified using a 5AZA-induced gene expression approach.

Impact: These breast cancer-relevant, FNA-optimized DNA methylation markers may have value as surrogate endpoint biomarkers in RP-FNA studies. Cancer Epidemiol Biomarkers Prev; 22(12); 2212–21. ©2013 AACR.
Data from A Novel Risk Locus at 6p21.3 for Epstein–Barr Virus-Positive Hodgkin Lymphoma
Authors: Delahaye-Sourdeix Manon , Urayama Kevin Y. , Gaborieau Valérie , Veenstra Rianne , Foll Matthieu , Chabrier Amelie , Benavente Yolanda , Nieters Alexandra , Becker Nikolaus , Foretova Lenka , Maynadié Marc , Staines Anthony , Smedby Karin Ekstrom , Glimelius Ingrid , Lightfoot Tracy , Cocco Pierluigi , Galan Pilar , Vatten Lars J. , Duell Eric J. , Kiemeney Lambertus , Roman Eve , de Sanjosé Silvia , Lathrop Mark , Melbye Mads , Brennan Paul , Diepstra Arjan , van den Berg Anke , Hjalgrim Henrik , Jarrett Ruth F. , McKay James D.
Published: April 2023

Abstract
Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region.

Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.

Results: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83–2.97; P = 7 × 10–12], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 0.92–1.21), indicating that this association was specific to the EBV-positive subgroup (Phet < P = 10−8). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histologic subtype of cHL.

Conclusions: rs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL.

Impact: This expands the number of genetic variants that are associated with cHL and provides additional evidence for a critical and specific role of EBV in the etiology of this disease. Cancer Epidemiol Biomarkers Prev; 24(12); 1838–43. ©2015 AACR.
Data from Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies
Authors: Yu Danxia , Takata Yumie , Smith-Warner Stephanie A. , Blot William , Sawada Norie , White Emily , Freedman Neal , Robien Kim , Giovannucci Edward , Zhang Xuehong , Park Yikyung , Gao Yu-Tang , Chlebowski Rowan T. , Langhammer Arnulf , Yang Gong , Severi Gianluca , Manjer Jonas , Khaw Kay-Tee , Weiderpass Elisabete , Liao Linda M. , Caporaso Neil , Krokstad Steinar , Hveem Kristian , Sinha Rashmi , Ziegler Regina , Tsugane Shoichiro , Xiang Yong-Bing , Johansson Mattias , Zheng Wei , Shu Xiao-Ou
Published: April 2023

Abstract
Background: Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival.

Methods: The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI).

Results: The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (<500–600 mg/d, less than half of the recommendation) was associated with a small increase in risk of death compared with recommended calcium intakes (800–1,200 mg/d); HR (95% CI) was 1.07 (1.01–1.13) after adjusting for age, stage, histology, grade, smoking status, pack-years, and other potential prognostic factors. The association between low calcium intake and higher lung cancer mortality was evident primarily among localized/regional stage patients, with HR (95% CI) of 1.15 (1.04–1.27). No association was found for supplemental calcium with survival in the multivariable-adjusted model.

Conclusions: This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients.

Impact: This multinational prospective study linked low calcium intake to lung cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(7); 1060–70. ©2017 AACR.