bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table 2 from 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium
Authors: Warren Helen , Dudbridge Frank , Fletcher Olivia , Orr Nick , Johnson Nichola , Hopper John L. , Apicella Carmel , Southey Melissa C. , Mahmoodi Maryam , Schmidt Marjanka K. , Broeks Annegien , Cornelissen Sten , Braaf Linda M. , Muir Kenneth R. , Lophatananon Artitaya , Chaiwerawattana Arkom , Wiangnon Surapon , Fasching Peter A. , Beckmann Matthias W. , Ekici Arif B. , Schulz-Wendtland Ruediger , Sawyer Elinor J. , Tomlinson Ian , Kerin Michael , Burwinkel Barbara , Marme Frederik , Schneeweiss Andreas , Sohn Christof , Guénel Pascal , Truong Thérèse , Laurent-Puig Pierre , Mulot Claire , Bojesen Stig E , Nielsen Sune F. , Flyger Henrik , Nordestgaard Børge G , Milne Roger L. , Benítez Javier , Arias-Pérez José-Ignacio , Zamora M. Pilar , Anton-Culver Hoda , Ziogas Argyrios , Bernstein Leslie , Dur Christina Clarke , Brenner Hermann , Müller Heiko , Arndt Volker , Langheinz Anne , Meindl Alfons , Golatta Michael , Bartram Claus R. , Schmutzler Rita K. , Brauch Hiltrud , Justenhoven Christina , Brüning Thomas , Chang-Claude Jenny , Wang-Gohrke Shan , Eilber Ursula , Dörk Thilo , Schürmann Peter , Bremer Michael , Hillemanns Peter , Nevanlinna Heli , Muranen Taru A. , Aittomäki Kristiina , Blomqvist Carl , Bogdanova Natalia , Antonenkova Natalia , Rogov Yuriy , Bermisheva Marina , Prokofyeva Darya , Zinnatullina Guzel , Khusnutdinova Elza , Lindblom Annika , Margolin Sara , Mannermaa Arto , Kosma Veli-Matti , Hartikainen Jaana M. , Kataja Vesa , Chenevix-Trench Georgia , Beesley Jonathan , Chen Xiaoqing , Lambrechts Diether , Smeets Ann , Paridaens Robert , Weltens Caroline , Flesch-Janys Dieter , Buck Katharina , Behrens Sabine , Peterlongo Paolo , Bernard Loris , Manoukian Siranoush , Radice Paolo , Couch Fergus J. , Vachon Celine , Wang Xianshu , Olson Janet , Giles Graham , Baglietto Laura , McLean Cariona A. , Severi Gianluca , John Esther M. , Miron Alexander , Winqvist Robert , Pylkäs Katri , Jukkola-Vuorinen Arja , Grip Mervi , Andrulis Irene L. , Knight Julia A. , Mulligan Anna Marie , Weerasooriya Nayana , Devilee Peter , Tollenaar Robert A.E.M. , Martens John W.M. , Seynaeve Caroline M. , Hooning Maartje J. , Hollestelle Antoinette , Jager Agnes , Tilanus-Linthorst Madeleine M.A. , Hall Per , Czene Kamila , Liu Jianjun , Li Jingmei , Cox Angela , Cross Simon S. , Brock Ian W. , Reed Malcolm W.R. , Pharoah Paul , Blows Fiona M. , Dunning Alison M. , Ghoussaini Maya , Ashworth Alan , Swerdlow Anthony , Jones Michael , Schoemaker Minouk , Easton Douglas F. , Humphreys Manjeet , Wang Qin , Peto Julian , dos-Santos-Silva Isabel
Published: March 2023

PDF file, 70K, Availability of information on tumor morphology and receptor status for Europeans, by each included BCAC study.
Supplementary Appendix 1 from Clinical Trials Methods for Evaluation of Potential Reduced Exposure Products
Authors: Hatsukami Dorothy K. , Hanson Karen , Briggs Anna , Parascandola Mark , Genkinger Jeanine M. , O'Connor Richard , Shields Peter G.
Published: March 2023

Supplementary Appendix 1 from Clinical Trials Methods for Evaluation of Potential Reduced Exposure Products
Supplementary Table 1 from Genetic Variation in the Vitamin D Receptor (VDR) and the Vitamin D–Binding Protein (GC) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry
Authors: Poynter Jenny N. , Jacobs Elizabeth T. , Figueiredo Jane C. , Lee Won H. , Conti David V. , Campbell Peter T. , Levine A. Joan , Limburg Paul , Le Marchand Loic , Cotterchio Michelle , Newcomb Polly A. , Potter John D. , Jenkins Mark A. , Hopper John L. , Duggan David J. , Baron John A. , Haile Robert W.
Published: March 2023

Supplementary Table 1 from Genetic Variation in the Vitamin D Receptor (VDR) and the Vitamin D–Binding Protein (GC) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry
Supplementary Table 3 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Authors: Prokunina-Olsson Ludmila , Fu Yi-Ping , Tang Wei , Jacobs Kevin B. , Hayes Richard B. , Kraft Peter , Berndt Sonja I. , Wacholder Sholom , Yu Kai , Hutchinson Amy , Spencer Feigelson Heather , Thun Michael J. , Diver W. Ryan , Albanes Demetrius , Virtamo Jarmo , Weinstein Stephanie , Schumacher Fredrick R. , Cancel-Tassin Geraldine , Cussenot Olivier , Valeri Antoine , Andriole Gerald L. , Crawford E. David , Haiman Christopher A. , Henderson Brian E. , Kolonel Laurence , Le Marchand Loic , Siddiq Afshan , Riboli Elio , Travis Ruth , Kaaks Rudolf , Isaacs William B. , Isaacs Sarah D. , Grönberg Henrik , Wiklund Fredrik , Xu Jianfeng , Vatten Lars J. , Hveem Kristian , Kumle Merethe , Tucker Margaret , Hoover Robert N. , Fraumeni Joseph F. , Hunter David J. , Thomas Gilles , Chatterjee Nilanjan , Chanock Stephen J. , Yeager Meredith
Published: March 2023

Supplementary Table 3 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Supplementary Table 1 from An Admixture Scan in 1,484 African American Women with Breast Cancer
Authors: Fejerman Laura , Haiman Christopher A. , Reich David , Tandon Arti , Deo Rahul C. , John Esther M. , Ingles Sue A. , Ambrosone Christine B. , Bovbjerg Dana Howard , Jandorf Lina H. , Davis Warren , Ciupak Gregory , Whittemore Alice S. , Press Michael F. , Ursin Giske , Bernstein Leslie , Huntsman Scott , Henderson Brian E. , Ziv Elad , Freedman Matthew L.
Published: March 2023

Supplementary Table 1 from An Admixture Scan in 1,484 African American Women with Breast Cancer
Data Supplement from Body Size, Physical Activity, Early-Life Energy Restriction, and Associations with Methylated Insulin-like Growth Factor–Binding Protein Genes in Colorectal Cancer
Authors: Simons Colinda C.J.M. , van den Brandt Piet A. , Stehouwer Coen D.A. , van Engeland Manon , Weijenberg Matty P.
Published: March 2023

Supplemental Table 1. Primer sequences used to analyze CpG island promoter hypermethylation of IGFBP2, IGFBP3, and IGFBP7 in colorectal tumors. Supplemental Table 2. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer by extent of IGFBP methylation in relation to body size, physical activity, and early life energy restriction in men in the Netherlands Cohort Study (1989-1993). Supplemental Table 3. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer by extent of IGFBP methylation in relation to body size, physical activity, and early life energy restriction in women in the Netherlands Cohort Study (1989-1993). Supplemental Table 4. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer by IGFBP2, IGFBP3, and IGFBP7 methylation status in relation to body size, physical activity, and early life energy restriction in the Netherlands Cohort Study (1989-1993).
Supplementary figures 1-4 from Changes in CpG Islands Promoter Methylation Patterns during Ductal Breast Carcinoma Progression
Authors: Hoque Mohammad Obaidul , Prencipe Maria , Poeta Maria Luana , Barbano Raffaela , Valori Vanna Maria , Copetti Massimiliano , Gallo Antonietta Pia , Brait Mariana , Maiello Evaristo , Apicella Adolfo , Rossiello Raffaele , Zito Francesco , Stefania Tommasi , Paradiso Angelo , Carella Massimo , Dallapiccola Bruno , Murgo Roberto , Carosi Illuminato , Bisceglia Michele , Fazio Vito Michele , Sidransky David , Parrella Paola
Published: March 2023

Supplementary figures 1-4 from Changes in CpG Islands Promoter Methylation Patterns during Ductal Breast Carcinoma Progression
Supplementary Data from Determinants of Breast Cancer Treatment Delay Differ for African American and White Women
Authors: McGee Sasha A. , Durham Danielle D. , Tse Chiu-Kit , Millikan Robert C.
Published: March 2023

PDF - 88KB, Supplementary data for the materials and methods section.
Supplementary Figure Legend from Polymorphisms in Inflammation Pathway Genes and Endometrial Cancer Risk
Authors: Delahanty Ryan J. , Xiang Yong-Bing , Spurdle Amanda , Beeghly-Fadiel Alicia , Long Jirong , Thompson Deborah , Tomlinson Ian , Yu Herbert , Lambrechts Diether , Dörk Thilo , Goodman Marc T. , Zheng Ying , Salvesen Helga B. , Bao Ping-Ping , Amant Frederic , Beckmann Matthias W. , Coenegrachts Lieve , Coosemans An , Dubrowinskaja Natalia , Dunning Alison , Runnebaum Ingo B. , Easton Douglas , Ekici Arif B. , Fasching Peter A. , Halle Mari K. , Hein Alexander , Howarth Kimberly , Gorman Maggie , Kaydarova Dylyara , Krakstad Camilla , Lose Felicity , Lu Lingeng , Lurie Galina , O'Mara Tracy , Matsuno Rayna K. , Pharoah Paul , Risch Harvey , Corssen Madeleine , Trovik Jone , Turmanov Nurzhan , Wen Wanqing , Lu Wei , Cai Qiuyin , Zheng Wei , Shu Xiao-Ou
Published: March 2023

PDF file - 48K
Supplementary Table 1 from Evolving Information Needs among Colon, Breast, and Prostate Cancer Survivors: Results from a Longitudinal Mixed-Effects Analysis
Authors: Tan Andy S.L. , Nagler Rebekah H. , Hornik Robert C. , DeMichele Angela
Published: March 2023

Supplementary Table 1. Adjusted odds ratios (mixed effects logistic model) of information seeking about cancer survivorship topics (excluded 554 patients who reported receiving treatment in round 2 and round 3 except hormonal therapy)
Supplementary Figure 1 from Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies
Authors: Chen Yi , Liu Lingxiao , Wang Xiaolin , Wang Jianhua , Yan Zhiping , Cheng Jieming , Gong Gaoquan , Li Guoping
Published: March 2023

PDF file - 778K, Figure S1: Funnel plot of studies evaluating the association between BMI and risk of overall gastric cancer (A and B), gastric cardia cancer (C and D) and gastric non-cardia cancer (E and F), Begg's regression asymmetry test.
Supplementary Figure 1 from Aberrant Vimentin Methylation Is Characteristic of Upper Gastrointestinal Pathologies
Authors: Moinova Helen , Leidner Rom S. , Ravi Lakshmeswari , Lutterbaugh James , Barnholtz-Sloan Jill S. , Chen Yanwen , Chak Amitabh , Markowitz Sanford D. , Willis Joseph E.
Published: March 2023

PDF file - 41K
Supplementary Methods, Supplementary Table, and Supplementary Figure from Review of Mass Spectrometry–Based Metabolomics in Cancer Research
Authors: Liesenfeld David B. , Habermann Nina , Owen Robert W. , Scalbert Augustin , Ulrich Cornelia M.
Published: March 2023

PDF - 217KB, Additional information regarding the search strategy used in the main paper. Supplementary Table: List of reported metabolites to be altered in human cancers. Supplementary Figure: General overview over the metabolomics workflow.
Data from Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings
Authors: Yang Nan , Eijsink Jasper J.H. , Lendvai Ágnes , Volders Haukeline H. , Klip Harry , Buikema Henk J. , van Hemel Bettien M. , Schuuring Ed , van der Zee Ate G.J. , Wisman G. Bea A.
Published: March 2023

Abstract
Purpose: Recently, we reported 13 possible cervical cancer–specific methylated biomarkers identified by pharmacologic unmasking microarray in combination with large-genome computational screening. The aim of the present study was to perform an in-depth analysis of the methylation patterns of these 13 candidate genes in cervical neoplasia and to determine their diagnostic relevance.

Experimental Design and Results: Five of the 13 gene promoters (C13ORF18, CCNA1, TFPI2, C1ORF166, and NPTX1) were found to be more frequently methylated in frozen cervical cancer compared with normal cervix specimens. Quantitative methylation analysis for these five markers revealed that both CCNA1 and C13ORF18 were methylated in 68 of 97 cervical scrapings from cervical cancer patients and in only 5 and 3 scrapings, respectively, from 103 healthy controls (P < 0.0005). In cervical scrapings from patients referred with an abnormal Pap smear, CCNA1 and C13ORF18 were methylated in 2 of 43 and 0 of 43 CIN 0 (no cervical intraepithelial neoplasia) and in 1 of 41 and 0 of 41 CIN I, respectively. Furthermore, 8 of 43 CIN II, 22 of 43 CIN III, and 3 of 3 microinvasive cancer patients were positive for both markers. Although sensitivity for CIN II or higher (for both markers 37%) was low, specificity (96% and 100%, respectively) and positive predictive value (92% and 100%, respectively) were high.

Conclusion: Methylation of CCNA1 and C13ORF18 in cervical scrapings is strongly associated with CIN II or higher-grade lesions. Therefore, these markers might be used for direct referral to gynecologists for patients with a methylation-positive scraping. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3000–7)
Data from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
Authors: Devaney James , Stirzaker Clare , Qu Wenjia , Song Jenny Z. , Statham Aaron L. , Patterson Kate I. , Horvath Lisa G. , Tabor Bruce , Coolen Marcel W. , Hulf Toby , Kench James G. , Henshall Susan M. , Pe Benito Ruth , Haynes Anne-Maree , Mayor Regina , Peinado Miguel A. , Sutherland Robert L. , Clark Susan J.
Published: March 2023

Abstract
Background: Previously, we showed that gene suppression commonly occurs across chromosome 2q14.2 in colorectal cancer, through a process of long-range epigenetic silencing (LRES), involving a combination of DNA methylation and repressive histone modifications. We now investigate whether LRES also occurs in prostate cancer across this 4-Mb region and whether differential DNA methylation of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers.

Methods: We used highly sensitive DNA methylation headloop PCR assays that can detect 10 to 25 pg of methylated DNA with a specificity of at least 1:1,000, and chromatin immunoprecipitation assays to investigate regional epigenetic remodeling across 2q14.2 in prostate cancer, in a cohort of 195 primary prostate tumors and 90 matched normal controls.

Results: Prostate cancer cells exhibit concordant deacetylation and methylation of histone H3 Lysine 9 (H3K9Ac and H3K9me2, respectively), and localized DNA hypermethylation of EN1, SCTR, and INHBB and corresponding loss of H3K27me3. EN1 and SCTR were frequently methylated (65% and 53%, respectively), whereas INHBB was less frequently methylated.

Conclusions: Consistent with LRES in colorectal cancer, we found regional epigenetic remodeling across 2q14.2 in prostate cancer. Concordant methylation of EN1 and SCTR was able to differentiate cancer from normal (P < 0.0001) and improved the diagnostic specificity of GSTP1 methylation for prostate cancer detection by 26%.

Impact: For the first time we show that DNA methylation of EN1 and SCTR promoters provide potential novel biomarkers for prostate cancer detection and in combination with GSTP1 methylation can add increased specificity and sensitivity to improve diagnostic potential. Cancer Epidemiol Biomarkers Prev; 20(1); 148–59. ©2011 AACR.
Data from International Efforts to Develop Biospecimen Best Practices
Authors: Vaught Jimmie B. , Caboux Elodie , Hainaut Pierre
Published: March 2023

Abstract
Variables introduced during the processes involved in biospecimen collection, processing, storage, and analysis are among the potential sources of bias in biomarker research. International efforts are under way to develop best practices to standardize biospecimen handling protocols. In general, documents on best practices address three major recurring themes: technical best practices on infrastructure and specimen handling, recommendations on informatics and data management, and recommendations on ethical, legal, and social issues. There are many areas of agreement among various international efforts, but no single set of practices has emerged as a unifying document. The ethical, legal, and social issues are particularly difficult to harmonize due to the many country-specific issues that are governed by a variety of local and federal rules and regulations. Given the increasingly international nature of research involving biomarkers and biospecimens, it will be necessary to continue to cooperate in the development of harmonized evidence-based best practices. Several international organizations including the International Cancer Genome Consortium are engaged in such efforts. Cancer Epidemiol Biomarkers Prev; 19(4); 912–5. ©2010 AACR.
Data from Polymorphisms in MicroRNAs Are Associated with Survival in Non–Small Cell Lung Cancer
Authors: Zhao Yang , Wei Qingyi , Hu Lingming , Chen Feng , Hu Zhibin , Heist Rebecca S. , Su Li , Amos Christopher I. , Shen Hongbing , Christiani David C.
Published: March 2023

Abstract
Background: MicroRNAs (miRNA) play important roles in the regulation of eukaryotic gene expression and are involved in human carcinogenesis. Single-nucleotide polymorphisms (SNP) in miRNA sequence may alter miRNA functions in gene regulation, which, in turn, may affect cancer risk and disease progression.

Methods: We conducted an analysis of associations of 142 miRNA SNPs with non–small cell lung cancer (NSCLC) survival using data from a genome-wide association study (GWAS) in a Caucasian population from the Massachusetts General Hospital (Boston, MA) including 452 early-stage and 526 late-stage NSCLC cases. Replication analyses were further performed in two external populations, one Caucasian cohort from The University of Texas MD Anderson Cancer Center (Houston, TX) and one Han Chinese cohort from Nanjing, China.

Results: We identified seven significant SNPs in the discovery set. Results from the independent Caucasian cohort demonstrated that the C allele of rs2042253 (hsa-miRNA-5197) was significantly associated with decreased risk for death among the patients with late-stage NSCLC (discovery set: HR, 0.80; P = 0.007; validation set: HR, 0.86; P = 0.035; combined analysis: HR, 0.87; P = 0.007).

Conclusions: These findings provide evidence that some miRNA SNPs are associated with NSCLC survival and can be used as predictive biomarkers.

Impact: This study provided an estimate of outcome probability for survival experience of patients with NSCLC, which demonstrates that genetic factors, as well as classic nongenetic factors, may be used to predict individual outcome. Cancer Epidemiol Biomarkers Prev; 23(11); 2503–11. ©2014 AACR.
Data from Prognostic Significance of Cytoplasmic p27 Expression in Human Melanoma
Authors: Chen Guangdi , Cheng Yabin , Zhang Zhizhong , Martinka Magdalena , Li Gang
Published: March 2023

Abstract
Background: The cyclin-dependent kinase inhibitor p27 plays important roles in cell proliferation, cell motility, and apoptosis. Interestingly, the nuclear and cytoplasmic p27 exert opposite biological functions. In this study, we investigated the prognostic impact of subcellular p27 expression.

Methods: We constructed melanoma tissue microarrays in a large series of melanoma patients, including 29 normal nevi, 52 dysplastic nevi, 270 primary melanomas, and 148 metastatic melanomas. The expression level of subcellular p27 in different stages of melanocytic lesions and its prognostic significance were evaluated.

Results: Compared with dysplastic nevi, nuclear p27 expression was remarkably reduced in primary melanomas and further reduced in metastatic melanoma (P < 0.001 for both), whereas cytoplasmic p27 expression is significantly increased from dysplastic nevi to primary melanomas (P = 0.032) and further increased in melanoma metastases (P = 0.037). Although loss of nuclear p27 expression is correlated with a worse 5-year survival of primary melanoma patients in Kaplan–Meier analysis (P = 0.046), it is not a prognostic factor by multivariate Cox regression analysis. On the contrary, Kaplan–Meier analysis showed that gain of cytoplasmic p27 was associated with a poor 5-year survival of metastatic melanoma patients (P < 0.001). Multivariate Cox regression analysis revealed that positive cytoplasmic p27 expression is an independent prognostic factor to predict metastatic melanoma patient outcome.

Conclusion: Cytoplasmic p27 may serve as a promising prognostic marker for metastatic melanoma.

Impact: Because there is no reliable prognostic marker for metastatic melanoma, our finding may have important clinical implications using cytoplasmic p27 as a prognostic biomarker for advanced melanoma. Cancer Epidemiol Biomarkers Prev; 20(10); 2212–21. ©2011 AACR.
Data from Genetic Polymorphisms in 15q25 and 19q13 Loci, Cotinine Levels, and Risk of Lung Cancer in EPIC
Authors: Timofeeva Maria N. , McKay James D. , Davey Smith George , Johansson Mattias , Byrnes Graham B. , Chabrier Amélie , Relton Caroline , Ueland Per Magne , Vollset Stein Emil , Midttun Øivind , Nygård Ottar , Slimani Nadia , Romieu Isabelle , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Fagherazzi Guy , Kaaks Rudolf , Teucher Birgit , Boeing Heiner , Weikert Cornelia , Bueno-de-Mesquita H. Bas , van Gils Carla , Peeters Petra H.M. , Agudo Antonio , Barricarte Aurelio , Huerta Jose-Maria , Rodríguez Laudina , Sánchez Maria-José , Larrañaga Nerea , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Travis Ruth C. , Gallo Valentina , Norat Teresa , Krogh Vittorio , Masala Giovanna , Panico Salvatore , Sacerdote Carlotta , Tumino Rosario , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Rasmuson Torgny , Hallmans Göran , Riboli Elio , Vineis Paolo , Brennan Paul
Published: March 2023

Abstract
Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genome-wide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels.

Methods: We conducted an analysis in a lung cancer case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13.

Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.

Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation.

Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior. Cancer Epidemiol Biomarkers Prev; 20(10); 2250–61. ©2011 AACR.
Data from Assessment of Automated Image Analysis of Breast Cancer Tissue Microarrays for Epidemiologic Studies
Authors: Bolton Kelly L. , Garcia-Closas Montserrat , Pfeiffer Ruth M. , Duggan Máire A. , Howat William J. , Hewitt Stephen M. , Yang Xiaohong R. , Cornelison Robert , Anzick Sarah L. , Meltzer Paul , Davis Sean , Lenz Petra , Figueroa Jonine D. , Pharoah Paul D.P. , Sherman Mark E.
Published: March 2023

Abstract
Background: A major challenge in studies of etiologic heterogeneity in breast cancer has been the limited throughput, accuracy, and reproducibility of measuring tissue markers. Computerized image analysis systems may help address these concerns, but published reports of their use are limited. We assessed agreement between automated and pathologist scores of a diverse set of immunohistochemical assays done on breast cancer tissue microarrays (TMA).

Methods: TMAs of 440 breast cancers previously stained for estrogen receptor (ER)-α, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER-β, and aromatase were independently scored by two pathologists and three automated systems (TMALab II, TMAx, and Ariol). Agreement between automated and pathologist scores of negative/positive was measured using the area under the receiver operating characteristics curve (AUC) and weighted κ statistics for categorical scores. We also investigated the correlation between immunohistochemical scores and mRNA expression levels.

Results: Agreement between pathologist and automated negative/positive and categorical scores was excellent for ER-α and PR (AUC range = 0.98-0.99; κ range = 0.86-0.91). Lower levels of agreement were seen for ER-β categorical scores (AUC = 0.99-1.0; κ = 0.80-0.86) and both negative/positive and categorical scores for aromatase (AUC = 0.85-0.96; κ = 0.41-0.67) and HER2 (AUC = 0.94-0.97; κ = 0.53-0.72). For ER-α and PR, there was a strong correlation between mRNA levels and automated (ρ = 0.67-0.74) and pathologist immunohistochemical scores (ρ = 0.67-0.77). HER2 mRNA levels were more strongly correlated with pathologist (ρ = 0.63) than automated immunohistochemical scores (ρ = 0.41-0.49).

Conclusions: Automated analysis of immunohistochemical markers is a promising approach for scoring large numbers of breast cancer tissues in epidemiologic investigations. This would facilitate studies of etiologic heterogeneity, which ultimately may allow improved risk prediction and better prevention approaches. Cancer Epidemiol Biomarkers Prev; 19(4); 992–9. ©2010 AACR.
Data from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Authors: Prokunina-Olsson Ludmila , Fu Yi-Ping , Tang Wei , Jacobs Kevin B. , Hayes Richard B. , Kraft Peter , Berndt Sonja I. , Wacholder Sholom , Yu Kai , Hutchinson Amy , Spencer Feigelson Heather , Thun Michael J. , Diver W. Ryan , Albanes Demetrius , Virtamo Jarmo , Weinstein Stephanie , Schumacher Fredrick R. , Cancel-Tassin Geraldine , Cussenot Olivier , Valeri Antoine , Andriole Gerald L. , Crawford E. David , Haiman Christopher A. , Henderson Brian E. , Kolonel Laurence , Le Marchand Loic , Siddiq Afshan , Riboli Elio , Travis Ruth , Kaaks Rudolf , Isaacs William B. , Isaacs Sarah D. , Grönberg Henrik , Wiklund Fredrik , Xu Jianfeng , Vatten Lars J. , Hveem Kristian , Kumle Merethe , Tucker Margaret , Hoover Robert N. , Fraumeni Joseph F. , Hunter David J. , Thomas Gilles , Chatterjee Nilanjan , Chanock Stephen J. , Yeager Meredith
Published: March 2023

Abstract
Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 × 10−6), with a suggestion of stronger association with aggressive disease (P = 1.2 × 10−7).

Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.

Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 × 10−11; ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 × 10−4 for aggressive cancer, n = 4,597; P = 3.25 × 10−8 for nonaggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657).

Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry.

Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349–55. ©2010 AACR.
Data from Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES Is Consistently Increased
Authors: Gonzalez Rachel M. , Daly Don S. , Tan Ruimin , Marks Jeffrey R. , Zangar Richard C.
Published: March 2023

Abstract
Background: Current biomarkers for breast cancer have little potential for detection. We determined whether breast cancer subtypes influence circulating protein biomarkers.

Methods: A sandwich ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated on the basis of breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses.

Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P < 0.01 for each analysis) in all four subtypes, with areas under the curve (AUC) for receiver operating characteristic values that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets.

Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true- and false-positive screens for breast cancer.

Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods. Cancer Epidemiol Biomarkers Prev; 20(7); 1543–51. ©2011 AACR.
Data from Intake of Cruciferous Vegetables Modifies Bladder Cancer Survival
Authors: Tang Li , Zirpoli Gary R. , Guru Khurshid , Moysich Kirsten B. , Zhang Yuesheng , Ambrosone Christine B. , McCann Susan E.
Published: March 2023

Abstract
Background: Intake of cruciferous vegetables, a rich source of dietary isothiocyanates, has been inversely associated with risk of bladder cancer. Due to the potent antiproliferative effects of dietary isothiocyanates on bladder cancer in in vitro and in vivo models, cruciferous vegetable intake may also play a role in survival among patients with bladder cancer.

Methods: Using information obtained from the Roswell Park Cancer Institute Tumor Registry, patient medical records, and routinely collected questionnaire data, we examined potential associations between intake of cruciferous vegetables and survival among bladder cancer patients. As cooking can substantially reduce or destroy isothiocyanates, consumption of raw versus cooked cruciferous vegetables was examined separately. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models.

Results: A total of 239 bladder cancer patients were included in the study. After an average of 8 years of follow-up, 179 deaths occurred, with 101 deaths attributable to bladder cancer. After adjustment for other prognostic factors, a strong and significant inverse association was observed between bladder cancer mortality and broccoli intake, in particular raw broccoli intake (≥1 versus <1 serving per month; HR for overall death, 0.57; 95% CI, 0.39-0.83; HR for disease-specific death, 0.43; 95% CI, 0.25-0.74). There were no significant associations for total vegetables, total fruits, or other individual cruciferous vegetables.

Conclusions: Considering the strong preclinical evidence, intake of broccoli may improve bladder cancer survival.

Impact: Further prospective investigation is warranted to confirm the potential role of cruciferous vegetables in bladder cancer prognosis. Cancer Epidemiol Biomarkers Prev; 19(7); 1806–11. ©2010 AACR.
Data from Genetic Variants in XRCC2: New Insights Into Colorectal Cancer Tumorigenesis
Authors: Curtin Karen , Lin Wei-Yu , George Rina , Katory Mark , Shorto Jennifer , Cannon-Albright Lisa A. , Smith Gillian , Bishop D. Timothy , Cox Angela , Camp Nicola J.
Published: March 2023

Abstract
Polymorphisms in DNA double-strand break repair gene XRCC2 may play an important role in colorectal cancer etiology, specifically in disease subtypes. Associations of XRCC2 variants and colorectal cancer were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, and Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases and 1,422 controls). The 14 variants studied were tagging single nucleotide polymorphisms (SNP) selected from National Institute of Environmental Health Sciences/HapMap data supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple colorectal cancer groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta-analyses of the total resource that includes family-based data. Similar to reports of colorectal cancer and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G>C, with increased risk of rectal tumors (odds ratio, 2.1; 95% confidence interval, 1.3-3.3; Pχ2 = 0.0006) versus controls, with the largest risk found for female rectal cases (odds ratio, 3.1; 95% confidence interval, 1.6-6.1; Pχ2 = 0.0006). This difference was significantly different to that for proximal and distal colon cancers (Pχ2 = 0.02). Our investigation supports a role for XRCC2 in colorectal cancer tumorigenesis, conferring susceptibility to rectal tumors. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2476–84)
Data from Can Lactase Persistence Genotype Be Used to Reassess the Relationship between Renal Cell Carcinoma and Milk Drinking? Potentials and Problems in the Application of Mendelian Randomization
Authors: Timpson Nicholas J. , Brennan Paul , Gaborieau Valérie , Moore Lee , Zaridze David , Matveev Vsevolod , Szeszenia-Dabrowska Neonilia , Lissowska Jolanta , Mates Dana , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Chow Wong-Ho , Rothman Nathaniel , Boffetta Paolo , Harbord Roger M. , Davey Smith George
Published: March 2023

Abstract
Background: Increased risk of renal cell carcinoma (RCC) with milk consumption has been reported from observational studies. Whether this represents a causal association or is a result of confounding or bias is unclear. We assessed the potential for using genetic variation in lactase persistence as a tool for the study of this relationship.

Methods: Using a large, hospital-based case-control study, we used observational, phenotypic, and genetic data to determine whether the MCM6 −13910 C/T(rs4988235) variant may be used as a nonconfounded and unbiased marker for milk consumption.

Results: Consumption of milk during adulthood was associated with increased risk of RCC [odds ratio (OR), 1.35; 95% confidence interval (95% CI), 1.03-1.76; P = 0.03]. Among controls, consumption of milk was associated with the lactase persistence genotype at rs4988235 (OR, 2.39; 95% CI, 1.81-3.15; P = 6.9 × 10−10); however, the same genotype was not associated with RCC (OR, 1.01; 95% CI, 0.83-1.22; P = 0.9). In controls, milk consumption was associated with confounding factors, including smoking and educational attainment, whereas genotypes at rs4988235 showed negligible association with confounding factors.

Conclusion: The absence of an association between the MCM6 genotype and RCC suggests that observational associations between milk consumption and RCC may be due to confounding or bias.

Impact: Although these data suggest that associations between milk consumption and RCC may be spurious, if the association between genotype and behavioral exposure is weak, then the power of this test may be low. The nature of intermediate risk factor instrumentation is an important consideration in the undertaking and interpretation of this type of causal analysis experiment. Cancer Epidemiol Biomarkers Prev; 19(5); 1341–8. ©2010 AACR.
Data from The Paracrine Hormone for the GUCY2C Tumor Suppressor, Guanylin, Is Universally Lost in Colorectal Cancer
Authors: Wilson Chantell , Lin Jieru E. , Li Peng , Snook Adam E. , Gong Jianping , Sato Takahiro , Liu Chengbao , Girondo Melanie A. , Rui Hallgeir , Hyslop Terry , Waldman Scott A.
Published: March 2023

Abstract
Background: Although colorectal cancer is a disease characterized by sequential accumulation of mutations in epithelial cells, mechanisms leading to genomic vulnerability contributing to tumor initiation remain undefined. GUCY2C has emerged as an intestine-specific tumor suppressor controlling epithelial homeostasis through circuits canonically disrupted in cancer. Surprisingly, the GUCY2C tumor suppressor is universally overexpressed by human colorectal cancer cells. This apparent paradox likely reflects silencing of GUCY2C through loss of its paracrine hormone guanylin. Here, we quantified expression of guanylin mRNA and protein in tumors and normal epithelia from patients with colorectal cancer.

Methods: Guanylin mRNA was quantified in tumors and normal adjacent epithelia from 281 patients by the reverse transcriptase-polymerase chain reaction. Separately, the guanylin protein was quantified by immunohistochemistry in 54 colorectal tumors and 30 specimens of normal intestinal epithelium.

Results: Guanylin mRNA in colorectum varied more than a 100-fold across the population. Guanylin mRNA was reduced 100- to 1,000-fold in >85% of tumors compared with matched normal adjacent mucosa (P < 0.001). Loss of guanylin mRNA was greatest in tumors from patients <50 years old (P < 0.005) and with the highest expression in normal adjacent mucosa (Spearman correlation coefficient = 0.61; P < 0.001). In a separate validation cohort, guanylin protein was detected in all 30 normal colorectal mucosa specimens, but in none of 54 colorectal tumors.

Conclusions: Colorectal cancer may initiate as a disease of paracrine hormone insufficiency through loss of guanylin expression, silencing the GUCY2C tumor suppressor and disrupting homeostatic mechanisms regulating colorectal epithelia cells.

Impact: Intestinal tumorigenesis may be prevented by oral GUCY2C hormone replacement therapy. Cancer Epidemiol Biomarkers Prev; 23(11); 2328–37. ©2014 AACR.
Data from Association of Cancer Susceptibility Variants with Risk of Multiple Primary Cancers: The Population Architecture using Genomics and Epidemiology Study
Authors: Park S. Lani , Caberto Christian P. , Lin Yi , Goodloe Robert J. , Dumitrescu Logan , Love Shelly-Ann , Matise Tara C. , Hindorff Lucia A. , Fowke Jay H. , Schumacher Fredrick R. , Beebe-Dimmer Jennifer , Chen Chu , Hou Lifang , Thomas Fridtjof , Deelman Ewa , Han Ying , Peters Ulrike , North Kari E. , Heiss Gerardo , Crawford Dana C. , Haiman Christopher A. , Wilkens Lynne R. , Bush William S. , Kooperberg Charles , Cheng Iona , Le Marchand Loïc
Published: March 2023

Abstract
Background: Multiple primary cancers account for approximately 16% of all incident cancers in the United States. Although genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC).

Methods: As part of the National Human Genome Research Institute (NHGRI) Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort (MEC) and Women's Health Initiative (WHI). Incident MPC (IMPC) cases (n = 1,385) were defined as participants diagnosed with more than one incident cancer after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n = 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the associations between 188 cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false-positive report probability (FPRP) to determine statistical significance.

Results: A nicotine dependence–associated and lung cancer variant, CHRNA3 rs578776 [OR, 1.16; 95% confidence interval (CI), 1.05–1.26; P = 0.004], and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR, 1.16; 95% CI, 1.04–1.28; P = 0.005 and OR, 1.13; 95% CI, 1.03–1.23; P = 0.006), were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (P < 0.05) after removing subjects who had lung or breast cancers, respectively (P ≤ 0.046). These associations did not show significant heterogeneity by smoking status (Pheterogeneity ≥ 0.53).

Conclusions: Our study has identified rs578776 and rs11249433 as risk variants for IMPC.

Impact: These findings may help to identify genetic regions associated with IMPC risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2568–78. ©2014 AACR.
Data from Gender Disparities in the Tumor Genetics and Clinical Outcome of Multiple Myeloma
Authors: Boyd Kevin D. , Ross Fiona M. , Chiecchio Laura , Dagrada GianPaolo , Konn Zoe J. , Tapper William J. , Walker Brian A. , Wardell Christopher P. , Gregory Walter M. , Szubert Alex J. , Davies Faith E. , Morgan Gareth J.
Published: March 2023

Abstract
Background: Several cancer types have differences in incidence and clinical outcome dependent on gender, but these are not well described in myeloma. The aim of this study was to characterize gender disparities in myeloma.

Methods: We investigated the association of gender with the prevalence of tumor genetic lesions and the clinical outcome of 1,960 patients enrolled in the phase III clinical trial MRC Myeloma IX. Genetic lesions were characterized by FISH.

Results: Disparities were found in the prevalence of primary genetic lesions with immunoglobulin heavy chain gene (IGH) translocations being more common in women (50% of female patients vs. 38% of male patients, P < 0.001) and hyperdiploidy being more common in men (50% female vs. 62% male, P < 0.001). There were also differences in secondary genetic events with del(13q) (52% female vs. 41% male, P < 0.001) and +1q (43% female vs. 36% male, P = 0.042) being found more frequently in female myeloma patients. Female gender was associated with inferior overall survival (median: 44.8 months female vs. 49.9 months male, P = 0.020).

Conclusions: We found gender-dependent differences in the prevalence of the primary genetic events of myeloma, with IGH translocations being more common in women and hyperdiploidy more common in men. This genetic background may impact subsequent genetic events such as +1q and del(13q), which were both more frequent in women. The higher prevalence of lesions associated with poor prognosis in the female myeloma population, such as t(4;14), t(14;16) and +1q, may adversely affect clinical outcome.

Impact: These differences suggest that gender influences the primary genetic events of myeloma. Cancer Epidemiol Biomarkers Prev; 20(8); 1703–7. ©2011 AACR.
Data from Comparison of Two Methods for Estimating Absolute Risk of Prostate Cancer Based on Single Nucleotide Polymorphisms and Family History
Authors: Hsu Fang-Chi , Sun Jielin , Zhu Yi , Kim Seong-Tae , Jin Tao , Zhang Zheng , Wiklund Fredrik , Kader A. Karim , Zheng S. Lilly , Isaacs William , Grönberg Henrik , Xu Jianfeng
Published: March 2023

Abstract
Disease risk–associated single nucleotide polymorphisms (SNP) identified from genome-wide association studies have the potential to be used for disease risk prediction. An important feature of these risk-associated SNPs is their weak individual effect but stronger cumulative effect on disease risk. Several approaches are commonly used to model the combined effect in risk prediction, but their performance is unclear. We compared two methods to model the combined effect of 14 prostate cancer risk–associated SNPs and family history for the estimation of absolute risk for prostate cancer in a population-based case-control study in Sweden (2,899 cases and 1,722 controls). Method 1 weighs each risk allele equally using a simple method of counting the number of risk alleles, whereas method 2 weighs each risk SNP differently based on its odds ratio. We found considerable differences between the two methods. Absolute risk estimates from method 1 were generally higher than those of method 2, especially among men at higher risk. The difference in the overall discriminative performance, measured by area under the curve of the receiver operating characteristic, was small between method 1 (0.614) and method 2 (0.618), P = 0.20. However, the performance of these two methods in identifying high-risk individuals (2- or 3-fold higher than average risk), measured by positive predictive values, was higher for method 2 than for method 1. These results suggest that method 2 is superior to method 1 in estimating absolute risk if the purpose of risk prediction is to identify high-risk individuals. Cancer Epidemiol Biomarkers Prev; 19(4); 1083–8. ©2010 AACR.
Data from Radon and Lung Cancer in the American Cancer Society Cohort
Authors: Turner Michelle C. , Krewski Daniel , Chen Yue , Pope C. Arden , Gapstur Susan , Thun Michael J.
Published: March 2023

Abstract
Background: Case–control studies conducted in North America, Europe, and Asia provided evidence of increased lung cancer risk due to radon in homes. Here, the association between residential radon and lung cancer mortality was examined in a large-scale cohort study.

Methods: Nearly 1.2 million Cancer Prevention Study-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment [mean (SD) = 53.5 Bq/m3 (38.0)]. Cox proportional hazards regression models were used to obtain adjusted HR and 95% CI for lung cancer mortality associated with radon. Potential effect modification by cigarette smoking, ambient sulfate concentrations, and other risk factors was assessed on both the additive and multiplicative scales.

Results: Through 1988, 3,493 lung cancer deaths were observed among 811,961 participants included in the analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (P = 0.02). A 15% (95% CI, 1–31) increase in the risk of lung cancer mortality was observed per 100 Bq/m3 increase in radon. Participants with mean radon concentrations above the EPA guideline value (148 Bq/m3) experienced a 34% (95% CI, 7–68) increase in risk for lung cancer mortality relative to those below the guideline value.

Conclusions: This large prospective study showed positive associations between ecological indicators of residential radon and lung cancer.

Impact: These results further support efforts to reduce radon concentrations in homes to the lowest possible level. Cancer Epidemiol Biomarkers Prev; 20(3); 438–48. ©2011 AACR.