bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from YAP and β-Catenin Cooperate to Drive Oncogenesis in Basal Breast Cancer
Authors: Quinn Hazel M. , Vogel Regina , Popp Oliver , Mertins Philipp , Lan Linxiang , Messerschmidt Clemens , Landshammer Alexandro , Lisek Kamil , Château-Joubert Sophie , Marangoni Elisabetta , Koren Elle , Fuchs Yaron , Birchmeier Walter
Published: March 2023

Abstract
Targeting cancer stem cells (CSC) can serve as an effective approach toward limiting resistance to therapies. While basal-like (triple-negative) breast cancers encompass cells with CSC features, rational therapies remain poorly established. We show here that the receptor tyrosine kinase Met promotes YAP activity in basal-like breast cancer and find enhanced YAP activity within the CSC population. Interfering with YAP activity delayed basal-like cancer formation, prevented luminal to basal transdifferentiation, and reduced CSC. YAP knockout mammary glands revealed a decrease in β-catenin target genes, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, nuclear YAP interacted with β-catenin and TEAD4 at gene regulatory elements. Proteomic patient data revealed an upregulation of the YAP signature in basal-like breast cancers. Our findings demonstrate that in basal-like breast cancers, β-catenin activity is dependent on YAP signaling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal-like breast cancers.
Significance:
These findings show that YAP cooperates with β-catenin in basal-like breast cancer to regulate CSCs and that targeting this interaction may be a novel CSC therapy for patients with basal-like breast cancer.
Data from NR2F1 Is a Barrier to Dissemination of Early-Stage Breast Cancer Cells
Authors: Rodriguez-Tirado Carolina , Kale Nupura , Carlini Maria J. , Shrivastava Nitisha , Rodrigues Alcina A. , Khalil Bassem D. , Bravo-Cordero Jose Javier , Hong Yan , Alexander Melissa , Ji Jiayi , Behbod Fariba , Sosa Maria Soledad
Published: March 2023

Abstract
Cancer cells can disseminate during very early and sometimes asymptomatic stages of tumor progression. Though biological barriers to tumorigenesis have been identified and characterized, the mechanisms that limit early dissemination remain largely unknown. We report here that the orphan nuclear receptor nuclear receptor subfamily 2, group F, member 1 (NR2F1)/COUP-TF1 serves as a barrier to early dissemination. NR2F1 expression was decreased in patient ductal carcinoma in situ (DCIS) samples. High-resolution intravital imaging of HER2+ early-stage cancer cells revealed that loss of function of NR2F1 increased in vivo dissemination and was accompanied by decreased E-cadherin expression, activation of wingless-type MMTV integration site family, member 1 (WNT)-dependent β-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial–mesenchymal transition (EMT) genes such as twist basic helix-loop-helix transcription factor 1 (TWIST1), zinc finger E-box binding homeobox 1 (ZEB1), and paired related homeobox 1 (PRRX1). Furthermore, downregulation of NR2F1 promoted a hybrid luminal/basal phenotype. NR2F1 expression was positively regulated by p38α signaling and repressed by HER2 and WNT4 pathways. Finally, early cancer cells with NR2F1LOW/PRRX1HIGH staining were observed in DCIS samples. Together, these findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 in early-stage breast cancer cells.
Significance:
During early stages of breast cancer progression, HER2-mediated suppression of NR2F1 promotes dissemination by inducing EMT and a hybrid luminal/basal-like program.
Data from IgA-Dominated Humoral Immune Responses Govern Patients' Outcome in Endometrial Cancer
Authors: Mandal Gunjan , Biswas Subir , Anadon Carmen M. , Yu Xiaoqing , Gatenbee Chandler D. , Prabhakaran Sandhya , Payne Kyle K. , Chaurio Ricardo A. , Martin Alexandra , Innamarato Patrick , Moran Carlos , Powers John J. , Harro Carly M. , Mine Jessica A. , Sprenger Kimberly B. , Rigolizzo Kristen E. , Wang Xuefeng , Curiel Tyler J. , Rodriguez Paulo C. , Anderson Alexander R. , Saglam Ozlen , Conejo-Garcia Jose R.
Published: March 2023

Abstract
Recent studies suggest that B cells could play an important role in the tumor microenvironment. However, the role of humoral responses in endometrial cancer remains insufficiently investigated. Using a cohort of 107 patients with different histological subtypes of endometrial carcinoma, we evaluated the role of coordinated humoral and cellular adaptive immune responses in endometrial cancer. Concomitant accumulation of T, B, and plasma cells at tumor beds predicted better survival. However, only B-cell markers corresponded with prolonged survival specifically in high-grade endometrioid type and serous tumors. Immune protection was associated with class-switched IgA and, to a lesser extent, IgG. Expressions of polymeric immunoglobulin receptor (pIgR) by tumor cells and its occupancy by IgA were superior predictors of outcome and correlated with defects in methyl-directed DNA mismatch repair. Mechanistically, pIgR-dependent, antigen-independent IgA occupancy drove activation of inflammatory pathways associated with IFN and TNF signaling in tumor cells, along with apoptotic and endoplasmic reticulum stress pathways, while thwarting DNA repair mechanisms. Together, these findings suggest that coordinated humoral and cellular immune responses, characterized by IgA:pIgR interactions in tumor cells, determine the progression of human endometrial cancer as well as the potential for effective immunotherapies.
Significance:
This study provides new insights into the crucial role of humoral immunity in human endometrial cancer, providing a rationale for designing novel immunotherapies against this prevalent malignancy.

See related commentary by Osorio and Zamarin, p. 766
Supplementary Figure 1 from Polymorphisms in the TOX3/LOC643714 Locus and Risk of Breast Cancer in African-American Women
Authors: Ruiz-Narváez Edward A. , Rosenberg Lynn , Cozier Yvette C. , Cupples L. Adrienne , Adams-Campbell Lucile L. , Palmer Julie R.
Published: March 2023

Supplementary Figure 1 from Polymorphisms in the TOX3/LOC643714 Locus and Risk of Breast Cancer in African-American Women
Supplementary Appendix 2 from Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy
Authors: Gupta Samir , Tong Liyue , Allison James E. , Carter Elizabeth , Koch Mark , Rockey Don C. , Anderson Paula , Ahn Chul , Argenbright Keith , Skinner Celette Sugg
Published: March 2023

Supplementary Appendix 2 from Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy
Supplementary Figure 1 from Novel Changes in Glycosylation of Serum Apo-J in Patients with Hepatocellular Carcinoma
Authors: Comunale Mary Ann , Wang Mengjun , Rodemich-Betesh Lucy , Hafner Julie , Lamontagne Anne , Klein Andrew , Marrero Jorge , Di Bisceglie Adrian M. , Gish Robert , Block Timothy , Mehta Anand
Published: March 2023

Supplementary Figure 1 from Novel Changes in Glycosylation of Serum Apo-J in Patients with Hepatocellular Carcinoma
Supplementary Table 2 from Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study
Authors: Campa Daniele , Mergarten Björn , De Vivo Immaculata , Boutron-Ruault Marie-Christine , Racine Antoine , Severi Gianluca , Nieters Alexandra , Katzke Verena A. , Trichopoulou Antonia , Yiannakouris Nikos , Trichopoulos Dimitrios , Boeing Heiner , Quirós J. Ramón , Duell Eric J. , Molina-Montes Esther , Huerta José María , Ardanaz Eva , Dorronsoro Miren , Khaw Kay-Tee , Wareham Nicholas , Travis Ruth C. , Palli Domenico , Pala Valeria , Tumino Rosario , Naccarati Alessio , Panico Salvatore , Vineis Paolo , Riboli Elio , Siddiq Afshan , Bueno-de-Mesquita H.B. , Peeters Petra H. , Nilsson Peter M. , Sund Malin , Ye Weimin , Lund Eiliv , Jareid Mie , Weiderpass Elisabete , Duarte-Salles Talita , Kong So Yeon , Stepien Magdalena , Canzian Federico , Kaaks Rudolf
Published: March 2023

Supplementary Table 2 - Associations between LTL and pancreatic cancer risk adjusted for Cpeptide and HbA1c levels considering only microscopically confirmed cases.
Supplementary Materials and Methods from Validity and Reliability of the Munsell Soil Color Charts for Assessing Human Skin Color
Authors: Reeder Anthony I. , Iosua Ella , Gray Andrew R. , Hammond Vanessa A.
Published: March 2023

Supplementary Materials and Methods
Supplementary Table 2 from Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis
Authors: Collin Simon M. , Metcalfe Chris , Zuccolo Luisa , Lewis Sarah J. , Chen Lina , Cox Angela , Davis Michael , Lane J. Athene , Donovan Jenny , Smith George Davey , Neal David E. , Hamdy Freddie C. , Gudmundsson Julius , Sulem Patrick , Rafnar Thorunn , Benediktsdottir Kristrun R. , Eeles Rosalind A. , Guy Michelle , Kote-Jarai Zsofia , Morrison Jonathan , Al Olama Ali Amin , Stefansson Kari , Easton Douglas F. , Martin Richard M.
Published: March 2023

Supplementary Table 2 from Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis
Supplementary Table 2 from Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) Polymorphism on Outcome of Advanced-Stage Squamous Cell Carcinoma of the Head and Neck Are Treatment Dependent
Authors: Zhong Shilong , Nukui Tomoko , Buch Shama , Diergaarde Brenda , Weissfeld Lisa A. , Grandis Jennifer , Romkes Marjorie , Weissfeld Joel L.
Published: March 2023

PDF file - 61K, Risk factor distributions according to ERCC2 genotype and CCND1 genotype.
Supplementary Table 1 from Selenium and Bladder Cancer Risk: a Meta-analysis
Authors: Amaral André F.S. , Cantor Kenneth P. , Silverman Debra T. , Malats Núria
Published: March 2023

Supplementary Table 1 from Selenium and Bladder Cancer Risk: a Meta-analysis
Supplementary Figure 2, Part 2 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

Supplementary Figure 2, Part 2 from Assessment of Automated Image Analysis of Breast Cancer Tissue Microarrays for Epidemiologic Studies
Supplementary Table and Figures 1-6 from Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
Authors: Oze Isao , Matsuo Keitaro , Suzuki Takeshi , Kawase Takakazu , Watanabe Miki , Hiraki Akio , Ito Hidemi , Hosono Satoyo , Ozawa Taijiro , Hatooka Shunzo , Yatabe Yasuhi , Hasegawa Yasuhisa , Shinoda Masayuki , Kiura Katsuyuki , Tajima Kazuo , Tanimoto Mitsune , Tanaka Hideo
Published: March 2023

Supplementary Table and Figures 1-6 from Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
Supplementary Figure 2 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

Supplementary Figure 2 from Intake of Cruciferous Vegetables Modifies Bladder Cancer Survival
Data from p53 Autoantibodies as Potential Detection and Prognostic Biomarkers in Serous Ovarian Cancer
Authors: Anderson Karen S. , Wong Jessica , Vitonis Allison , Crum Christopher P. , Sluss Patrick M. , LaBaer Joshua , Cramer Daniel
Published: March 2023

Abstract
Background: This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer.

Methods: p53-AAb were detected by ELISA in sera obtained preoperatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (n = 60), nonserous ovarian cancers (n = 30), and women with benign disease (n = 30). Age-matched controls were selected from the general population (n = 120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival.

Results: p53-AAb were detected in 25 of 60 (41.7%) of serous cases, 4 of 30 (13.3%) nonserous cases, 3 of 30 (10%) benign disease cases, and 10 of 120 (8.3%) controls (combined P = 0.0002). p53-AAb did not significantly improve the detection of cases [area under the curve (AUC), 0.69] or the discrimination of benign versus malignant disease (AUC, 0.64) compared with CA 125 (AUC, 0.99) or HE4 (AUC, 0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (P = 0.01). Detectable p53 antibodies in pretreatment sera were correlated with improved overall survival (P = 0.04; hazard ratio, 0.57; 95% confidence interval, 0.33-0.97) in serous ovarian cancer.

Conclusions: Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer.

Impact: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival. Cancer Epidemiol Biomarkers Prev; 19(3); 859–68
Data from Fine-Mapping IGF1 and Prostate Cancer Risk in African Americans: The Multiethnic Cohort Study
Authors: Giorgi Elena E. , Stram Daniel O. , Taverna Darin , Turner Stephen D. , Schumacher Fredrick , Haiman Christopher A. , Lum-Jones Annette , Tirikainen Maarit , Caberto Christian , Duggan David , Henderson Brian E. , Le Marchand Loic , Cheng Iona
Published: March 2023

Abstract
Genetic variation at insulin-like growth factor 1 (IGF1) has been linked to prostate cancer risk. However, the specific predisposing variants have not been identified. In this study, we fine-mapped the IGF1 locus for prostate cancer risk in African Americans. We conducted targeted Roche GS-Junior 454 resequencing of a 156-kb region of IGF1 in 80 African American aggressive prostate cancer cases. Three hundred and thirty-four IGF1 SNPs were examined for their association with prostate cancer risk in 1,000 African American prostate cancer cases and 991 controls. The top associated SNP in African Americans, rs148371593, was examined in an additional 3,465 prostate cancer cases and 3,425 controls of non-African American ancestry—European Americans, Japanese Americans, Latinos, and Native Hawaiians. The overall association of 334 IGF1 SNPs and prostate cancer risk was assessed using logistic kernel-machine methods. The association between each SNP and prostate cancer risk was evaluated through unconditional logistic regression. A false discovery rate threshold of q < 0.1 was used to determine statistical significance of associations. We identified 8 novel IGF1 SNPs. The cumulative effect of the 334 IGF1 SNPs was not associated with prostate cancer risk (P = 0.13) in African Americans. Twenty SNPs were nominally associated with prostate cancer at P < 0.05. The top associated SNP among African Americans, rs148371593 [minor allele frequency (MAF) = 0.03; P = 0.0014; q > 0.1], did not reach our criterion of statistical significance. This polymorphism was rare in non-African Americans (MAF < 0.003) and was not associated with prostate cancer risk (P = 0.98). Our findings do not support the role of IGF1 variants and prostate cancer risk among African Americans. Cancer Epidemiol Biomarkers Prev; 23(9); 1928–32. ©2014 AACR.
Data from Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) Polymorphism on Outcome of Advanced-Stage Squamous Cell Carcinoma of the Head and Neck Are Treatment Dependent
Authors: Zhong Shilong , Nukui Tomoko , Buch Shama , Diergaarde Brenda , Weissfeld Lisa A. , Grandis Jennifer , Romkes Marjorie , Weissfeld Joel L.
Published: March 2023

Abstract
Background: Germline variation in DNA damage response may explain variable treatment outcomes in squamous cell carcinoma of the head and neck (SCCHN). By grouping patients according to stage and radiation treatment, we compared SCCHN survival with regard to ERCC2 A35931C (Lys751Gln, rs13181) and CCND1 G870A (Pro241Pro, rs9344) genotypes.

Methods: In a hospital-based SCCHN case series (all white, 24.7% female, mean age 58.4 years), this treatment-outcome cohort study genotyped 275 stage III–IV cases that were initially treated with radiation (with or without chemotherapy) and 80 stage III–IV and 130 stage I–II cases that were initially treated without radiation or chemotherapy and used Kaplan–Meier and Cox regression analyses to compare genotype groups on the basis of overall, disease-specific, progression-free, and recurrence-free survival rates.

Results:ERCC2 35931 AA predicted worse survival in stage III–IV cases treated with radiation [multiply-adjusted HR = 1.66, 95% confidence interval (CI), 1.15–2.40; HR over the first 3 follow-up years = 1.92; 95% CI, 1.28–2.88] and better survival in stage III–IV cases not treated with radiation (HR = 0.26; 95% CI, 0.11–0.62). Although not associated with survival in stage III–IV cancers treated with radiation (HR = 1.00; 95% CI, 0.67–1.51), CCND1-870 GG predicted better survival in stage III–IV cancers not treated with radiation (HR = 0.14; 95% CI, 0.04–0.50). Survival in stage I–II did not depend on ERCC2 A35931C or CCND1 G870A genotype.

Conclusions: Although promoting tumor progression in untreated patients, germline differences in DNA-repair or cell-cycle control may improve treatment outcome in patients treated with DNA-damaging agents.

Impact:ERCC2 A35931C may help distinguish advanced stage SCCHN with better outcomes from radiation treatment. Cancer Epidemiol Biomarkers Prev; 20(11); 2429–37. ©2011 AACR.
Data from Validating Self-Reported Mammography Use in Vulnerable Communities: Findings and Recommendations
Authors: Allgood Kristi L. , Rauscher Garth H. , Whitman Steven , Vasquez-Jones Giselle , Shah Ami M.
Published: March 2023

Abstract
Background: Most health surveys ask women whether they have had a recent mammogram, all of which report mammography use (past 2 years) at about 70% to 80% regardless of race or residence. We examined the potential extent of overreporting of mammography use in low income African-American and Latina women, and whether self-report inaccuracies might bias estimated associations between patient characteristics and mammography use.

Methods: Using venue-based sampling in two poor communities on the west side of Chicago, we asked eligible women living in two west side communities of Chicago to complete a survey about breast health (n = 2,200) and to provide consent to view their medical record. Of the 1,909 women who screened eligible for medical record review, 1,566 consented (82%). We obtained medical records of all women who provided both permission and a valid local mammography facility (n = 1,221). We compared the self-reported responses from the survey with the imaging reports found in the medical record (documented). To account for missing data, we conducted multiple imputations for key demographic variables and report standard measures of accuracy.

Results: Although 73% of women self-reported a mammogram in the last 2 years, only 44% of self-reports were documented. Overreporting of mammography use was observed for all three ethnic groups.

Conclusions: These results suggest considerable overestimation of prevalence of use in these vulnerable populations.

Impact: Relying on known faulty self-reported mammography data as a measure of mammography use provides an overly optimistic picture of utilization, a problem that may be exacerbated in vulnerable minority communities. Cancer Epidemiol Biomarkers Prev; 23(8); 1649–58. ©2014 AACR.
Data from Inherited Variants in Mitochondrial Biogenesis Genes May Influence Epithelial Ovarian Cancer Risk
Authors: Permuth-Wey Jennifer , Chen Y. Ann , Tsai Ya-Yu , Chen Zhihua , Qu Xiaotao , Lancaster Johnathan M. , Stockwell Heather , Dagne Getachew , Iversen Edwin , Risch Harvey , Barnholtz-Sloan Jill , Cunningham Julie M. , Vierkant Robert A. , Fridley Brooke L. , Sutphen Rebecca , McLaughlin John , Narod Steven A. , Goode Ellen L. , Schildkraut Joellen M. , Fenstermacher David , Phelan Catherine M. , Sellers Thomas A.
Published: March 2023

Abstract
Background: Mitochondria contribute to oxidative stress, a phenomenon implicated in ovarian carcinogenesis. We hypothesized that inherited variants in mitochondrial-related genes influence epithelial ovarian cancer (EOC) susceptibility.

Methods: Through a multicenter study of 1,815 Caucasian EOC cases and 1,900 controls, we investigated associations between EOC risk and 128 single nucleotide polymorphisms (SNPs) from 22 genes/regions within the mitochondrial genome (mtDNA) and 2,839 nuclear-encoded SNPs localized to 138 genes involved in mitochondrial biogenesis (BIO, n = 35), steroid hormone metabolism (HOR, n = 13), and oxidative phosphorylation (OXP, n = 90) pathways. Unconditional logistic regression was used to estimate OR and 95% CI between genotype and case status. Overall significance of each gene and pathway was evaluated by using Fisher's method to combine SNP-level evidence. At the SNP level, we investigated whether lifetime ovulation, hormone replacement therapy (HRT), and cigarette smoking were confounders or modifiers of associations.

Results: Interindividual variation involving BIO was most strongly associated with EOC risk (empirical P = 0.050), especially for NRF1, MTERF, PPARGC1A, ESRRA, and CAMK2D. Several SNP-level associations strengthened after adjustment for nongenetic factors, particularly for MTERF. Statistical interactions with cigarette smoking and HRT use were observed with MTERF and CAMK2D SNPs, respectively. Overall variation within mtDNA, HOR, and OXP was not statistically significant (empirical P > 0.10).

Conclusion: We provide novel evidence to suggest that variants in mitochondrial biogenesis genes may influence EOC susceptibility.

Impact: A deeper understanding of the complex mechanisms implicated in mitochondrial biogenesis and oxidative stress may aid in developing strategies to reduce morbidity and mortality from EOC. Cancer Epidemiol Biomarkers Prev; 20(6); 1131–45. ©2011 AACR.
Data from Genetic Variation in IGF2 and HTRA1 and Breast Cancer Risk among BRCA1 and BRCA2 Carriers
Authors: Neuhausen Susan L. , Brummel Sean , Ding Yuan Chun , Steele Linda , Nathanson Katherine L. , Domchek Susan , Rebbeck Timothy R. , Singer Christian F. , Pfeiler Georg , Lynch Henry T. , Garber Judy E. , Couch Fergus , Weitzel Jeffrey N. , Godwin Andrew , Narod Steven A. , Ganz Patricia A. , Daly Mary B. , Isaacs Claudine , Olopade Olufunmilayo I. , Tomlinson Gail E. , Rubinstein Wendy S. , Tung Nadine , Blum Joanne L. , Gillen Daniel L.
Published: March 2023

Abstract
Background:BRCA1 and BRCA2 mutation carriers have a lifetime breast cancer risk of 40% to 80%, suggesting the presence of risk modifiers. We previously identified significant associations in genetic variants in the insulin-like growth factor (IGF) signaling pathway. Here, we investigate additional IGF signaling genes as risk modifiers for breast cancer development in BRCA carriers.

Methods: A cohort of 1,019 BRCA1 and 500 BRCA2 mutation carriers were genotyped for 99 single-nucleotide polymorphisms (SNP) in 13 genes. Proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was used. For an SNP analysis, no additivity assumptions were made.

Results: Significant associations were found between risk of breast cancer and LD blocks in IGF2 for BRCA1 and BRCA2 mutation carriers (global P values of 0.009 for BRCA1 and 0.007 for BRCA2), HTRA1 for BRCA1 carriers (global P value of 0.005), and MMP3 for BRCA2 carriers (global P = 0.0000007 for BRCA2).

Conclusions: We identified significant associations of genetic variants involved in IGF signaling. With the known interaction of BRCA1 and IGF signaling and the loss of PTEN in a majority of BRCA1 tumors, this suggests that signaling through AKT may modify breast cancer risk in BRCA1 carriers.

Impact: These results suggest potential avenues for future research targeting the IGF signaling pathway in modifying risk in BRCA1and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 20(8); 1690–702. ©2011 AACR.
Data from Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma
Authors: Wu Chih-Ching , Chang Ya-Ting , Chang Kai-Ping , Liu Yu-Ling , Liu Hao-Ping , Lee I-Ling , Yu Jau-Song , Chiang Wei-Fan
Published: March 2023

Abstract
Background: Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide, and its incidence is still increasing. Approximately 50% of patients with OSCC die within 5 years after diagnosis, mostly ascribed to the fact that the majority of patients present advanced stages of OSCC at the time of diagnosis.

Methods: To discover salivary biomarkers for ameliorating the detection of OSCC, herein, we developed a multiplexed bead-based platform to simultaneously detect auto-antibodies (auto-Abs) in salivary samples.

Results: Compared with healthy individuals, the salivary levels of anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0 were significantly elevated in patients with OSCC. Noteworthily, the elevated levels of anti-p53, anti-survivin, and anti-Hsp60 were already observed in individuals with oral potentially malignant disorder. Moreover, the salivary levels of anti-p53, anti-survivin, anti-Hsp60, anti-RPLP0, and anti-CK8 were significantly elevated in patients with early-stage OSCC compared with those in healthy individuals. Most importantly, the use of a combined panel of salivary anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0 largely improves the detection of OSCC.

Conclusion: Collectively, our results reveal that the salivary auto-Abs are effective OSCC biomarkers and the four-auto-Ab panel provides a novel and practicable approach for OSCC screening.

Impact: This study provides the first evidence for the potential clinical application of salivary auto-Abs in OSCC diagnosis. Cancer Epidemiol Biomarkers Prev; 23(8); 1569–78. ©2014 AACR.
Data from The Role of Genome Sequencing in Personalized Breast Cancer Prevention
Authors: Sieh Weiva , Rothstein Joseph H. , McGuire Valerie , Whittemore Alice S.
Published: March 2023

Abstract
Background: There is uncertainty about the benefits of using genome-wide sequencing to implement personalized preventive strategies at the population level, with some projections suggesting little benefit. We used data for all currently known breast cancer susceptibility variants to assess the benefits and harms of targeting preventive efforts to a population subgroup at highest genomic risk of breast cancer.

Methods: We used the allele frequencies and effect sizes of 86 known breast cancer variants to estimate the population distribution of breast cancer risks and evaluate the strategy of targeting preventive efforts to those at highest risk. We compared the efficacy of this strategy with that of a “best-case” strategy based on a risk distribution estimated from breast cancer concordance in monozygous twins, and with strategies based on previously estimated risk distributions.

Results: Targeting those in the top 25% of the risk distribution would include approximately half of all future breast cancer cases, compared with 70% captured by the best-case strategy and 35% based on previously known variants. In addition, current evidence suggests that reducing exposure to modifiable nongenetic risk factors will have greatest benefit for those at highest genetic risk.

Conclusions: These estimates suggest that personalized breast cancer preventive strategies based on genome sequencing will bring greater gains in disease prevention than previously projected. Moreover, these gains will increase with increased understanding of the genetic etiology of breast cancer.

Impact: These results support the feasibility of using genome-wide sequencing to target the women who would benefit from mammography screening. Cancer Epidemiol Biomarkers Prev; 23(11); 2322–7. ©2014 AACR.
Data from Circulating Mitochondrial DNA Level, a Noninvasive Biomarker for the Early Detection of Gastric Cancer
Authors: Fernandes Julien , Michel Valérie , Camorlinga-Ponce Margarita , Gomez Alejandro , Maldonado Carmen , De Reuse Hilde , Torres Javier , Touati Eliette
Published: March 2023

Abstract
Background: Gastric cancer represents a major health burden worldwide and is often diagnosed at an advanced stage. Biomarkers for screening and prevention of gastric cancer are missing. Changes in peripheral blood mitochondrial DNA (mtDNA) have emerged as a potential preventive/diagnosis biomarker for cancer risk. We aimed to determine whether peripheral leukocytes mtDNA levels are associated with stages of the gastric carcinogenesis cascade.

Methods: We measured mtDNA by quantitative real-time PCR assay in peripheral leukocytes of 28 patients with non-atrophic gastritis (NAG), 74 patients with gastric cancer, and 48 matched asymptomatic controls. In parallel, the serologic level of IL8 was determined.

Results: Mean mtDNA level was higher in patients with gastric cancer (P = 0.0095) than in controls, with values >8.46 significantly associated with gastric cancer (OR, 3.93). Three ranges of mtDNA values were identified: interval I, <2.0; interval II, 2.0–20; and interval III, >20. Interval I included mainly NAG cases, and few gastric cancer samples and interval III corresponded almost exclusively to patients with gastric cancer. All controls fell in interval II, together with some NAG and gastric cancer cases. IL8 levels were significantly higher in patients with gastric cancer (P < 0.05), with levels >50 pg/mL observed exclusively in patients with gastric cancer, allowing to distinguish them within interval II. We validated mtDNA results in a second cohort of patients, confirming that mtDNA was significantly higher in gastric cancer than in patients with preneoplasia.

Conclusions: Circulating levels of mtDNA and IL8 constitute a potential biomarker for the early detection of gastric cancer.

Impact: Our findings lead us to propose a new noninvasive method to detect patients with gastric cancer risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2430–8. ©2014 AACR.
Data from Association of Insurance and Race/Ethnicity with Disease Severity among Men Diagnosed with Prostate Cancer, National Cancer Database 2004-2006
Authors: Fedewa Stacey A. , Etzioni Ruth , Flanders W. Dana , Jemal Ahmedin , Ward Elizabeth M.
Published: March 2023

Abstract
Background: Previous studies documenting variations in severity of prostate cancer at diagnosis by race/ethnicity and insurance status have been limited to small sample sizes and patients ≥65 years of age. This study examines disease severity among patients ages 18 to 99 from the National Cancer Database (NCDB).

Methods: Patients diagnosed between 2004 and 2006 with prostate cancer were selected from the NCDB (n = 312,339). We evaluated the association among three disease severity measures: prostate specific antigen (PSA) level, Gleason score 8 to 10, and clinical T-stage 3/4, by race/ethnicity and insurance while adjusting for sociodemographic and clinical factors.

Results: Uninsured and Medicaid-insured patients had elevated PSA levels, higher odds of advanced Gleason score [uninsured odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.82-2.12; Medicaid OR, 1.67; 95% CI, 1.55-1.79], and advanced clinical T stage (uninsured OR, 1.85; 95% CI, 1.69-2.03; Medicaid OR, 1.49; 95% CI, 1.35-1.63) compared with privately insured patients. Black (OR, 1.19; 95% CI, 1.15-1.23), Hispanic (OR, 1.16; 95% CI, 1.10-1.23), and Asian patients (OR, 1.22; 95% CI, 1.24-1.43) had higher odds of advanced Gleason score and similar odds of advanced stage of disease relative to whites.

Conclusion: Insurance status is strongly associated with disease severity among prostate cancer patients.

Impact: Strong associations between insurance and disease severity may be related to lack of access to preventive services such as PSA screening and barriers to medical evaluation. Although the risks and benefits of PSA screening have not been fully elucidated, it is important that all men have the opportunity to be informed about this option and preventative medical services. Cancer Epidemiol Biomarkers Prev; 19(10); 2437–44. ©2010 AACR.
Data from Tumor and Salivary Matrix Metalloproteinase Levels Are Strong Diagnostic Markers of Oral Squamous Cell Carcinoma
Authors: Stott-Miller Marni , Houck John R. , Lohavanichbutr Pawadee , Méndez Eduardo , Upton Melissa P. , Futran Neal D. , Schwartz Stephen M. , Chen Chu
Published: March 2023

Abstract
Background: The matrix metalloproteinases (MMP) cause degradation of the extracellular matrix and basement membranes, and thus may play a key role in cancer development.

Methods: In our search for biomarkers for oral squamous cell carcinomas (OSCC), we compared primary OSCC, oral dysplasia and control subjects with respect to: (i) expression of MMP1, MMP3, MMP10, and MMP12 in oral epithelial tissue using Affymetrix U133 2.0 Plus GeneChip arrays, followed by quantitative reverse transcription-PCR (qRT-PCR) for MMP1, and (ii) determination of MMP1 and MMP3 concentrations in saliva.

Results:MMP1 expression in primary OSCC (n = 119) was >200-fold higher (P = 7.16 × 10−40) compared with expression levels in nonneoplastic oral epithelium from controls (n = 35). qRT-PCR results on 30 cases and 22 controls confirmed this substantial differential expression. The exceptional discriminatory power to separate OSCC from controls was validated in two independent testing sets (AUC% = 100; 95% CI: 100–100 and AUC% = 98.4; 95% CI: 95.6–100). Salivary concentrations of MMP1 and MMP3 in OSCC patients (33 stage I/II, 26 stage III/IV) were 6.2 times (95% CI: 3.32–11.73) and 14.8 times (95% CI: 6.75–32.56) higher, respectively, than in controls, and displayed an increasing trend with higher stage disease.

Conclusion: Tumor and salivary MMPs are robust diagnostic biomarkers of OSCC.

Impact: The capacity of MMP gene expression to identify OSCC provides support for further investigation into MMPs as potential markers for OSCC development. Detection of MMP proteins in saliva in particular may provide a promising means to detect and monitor OSCC noninvasively. Cancer Epidemiol Biomarkers Prev; 20(12); 2628–36. ©2011 AACR.
Data from A Risk Prediction Model for Smoking Experimentation in Mexican American Youth
Authors: Talluri Rajesh , Wilkinson Anna V. , Spitz Margaret R. , Shete Sanjay
Published: March 2023

Abstract
Background: Smoking experimentation in Mexican American youth is problematic. In light of the research showing that preventing smoking experimentation is a valid strategy for smoking prevention, there is a need to identify Mexican American youth at high risk for experimentation.

Methods: A prospective population-based cohort of 1,179 adolescents of Mexican descent was followed for 5 years starting in 2005–06. Participants completed a baseline interview at a home visit followed by three telephone interviews at intervals of approximately 6 months and additional interviews at two home visits in 2008–09 and 2010–11. The primary endpoint of interest in this study was smoking experimentation. Information about social, cultural, and behavioral factors (e.g., acculturation, susceptibility to experimentation, home characteristics, and household influences) was collected at baseline using validated questionnaires.

Results: Age, sex, cognitive susceptibility, household smoking behavior, peer influence, neighborhood influence, acculturation, work characteristics, positive outcome expectations, family cohesion, degree of tension, ability to concentrate, and school discipline were found to be associated with smoking experimentation. In a validation dataset, the proposed risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.719 (95% confidence interval, 0.637–0.801) for predicting absolute risk for smoking experimentation within 1 year.

Conclusions: The proposed risk prediction model is able to quantify the risk of smoking experimentation in Mexican American adolescents.

Impact: Accurately identifying Mexican American adolescents who are at higher risk for smoking experimentation who can be intervened will substantially reduce the incidence of smoking and thereby subsequent health risks. Cancer Epidemiol Biomarkers Prev; 23(10); 2165–74. ©2014 AACR.
Data from Impact of EGFR Genetic Variants on Glioma Risk and Patient Outcome
Authors: Costa Bruno Marques , Viana-Pereira Marta , Fernandes Ricardo , Costa Sandra , Linhares Paulo , Vaz Rui , Pinheiro Céline , Lima Jorge , Soares Paula , Silva Ana , Pardal Fernando , Amorim Júlia , Nabiço Rui , Almeida Rui , Alegria Carlos , Pires Manuel Melo , Pinheiro Célia , Carvalho Ernesto , Oliveira Pedro , Lopes José M. , Reis Rui M.
Published: March 2023

Abstract
Background: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, −216G/T and −191C/A, and a polymorphic (CA)n microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis.

Methods: We conducted a case–control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed.

Results: None of the EGFR −216G/T variants was significantly associated with glioma risk. The −191C/A genotype was associated with higher risk for glioma when the (CA)n alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)n repeat cutoff point used, shorter (CA)n repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)n cutoff points, only −191C/A genotype was consistently associated with improved survival of patients with glioblastoma.

Conclusions: Our findings implicate EGFR −191C/A and the (CA)n repeat polymorphisms as risk factors for gliomas, and suggest −191C/A as a prognostic marker in glioblastoma.

Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies. Cancer Epidemiol Biomarkers Prev; 20(12); 2610–7. ©2011 AACR.
Data from Genetic Variants of Methyl Metabolizing Enzymes and Epigenetic Regulators: Associations with Promoter CpG Island Hypermethylation in Colorectal Cancer
Authors: de Vogel Stefan , Wouters Kim A.D. , Gottschalk Ralph W.H. , van Schooten Frederik J. , de Goeij Anton F.P.M. , de Bruïne Adriaan P. , Goldbohm Royle A. , van den Brandt Piet A. , Weijenberg Matty P. , van Engeland Manon
Published: March 2023

Abstract
Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of folate metabolizing enzymes (MTHFR, MTR, and MTRR), DNA methyltransferase DNMT3b, and histone methyltransferases (EHMT1, EHMT2, and PRDM2), with colorectal cancers, with or without the CpG island methylator phenotype (CIMP), MLH1 hypermethylation, or microsatellite instability. Incidence rate ratios were calculated in case-cohort analyses, with common homozygotes as reference, among 659 cases and 1,736 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852). Men with the MTHFR 677TT genotype were at decreased colorectal cancer risk (incidence rate ratio, 0.49; P = 0.01), but the T allele was associated with increased risk in women (incidence rate ratio, 1.39; P = 0.02). The MTR 2756GG genotype was associated with increased colorectal cancer risk (incidence rate ratio, 1.58; P = 0.04), and inverse associations were observed among women carrying DNMT3b C→T (rs406193; incidence rate ratio, 0.72; P = 0.04) or EHMT2 G→A (rs535586; incidence rate ratio, 0.76; P = 0.05) polymorphisms. Although significantly correlated (P < 0.001), only 41.5% and 33.3% of CIMP tumors harbored MLH1 hypermethylation or microsatellite instability, respectively. We observed inverse associations between MTR A2756G and CIMP among men (incidence rate ratio, 0.58; P = 0.04), and between MTRR A66G and MLH1 hypermethylation among women (incidence rate ratio, 0.55; P = 0.02). In conclusion, MTHFR, MTR, DNMT3b, and EHMT2 polymorphisms are associated with colorectal cancer, and rare variants of MTR and MTRR may reduce promoter hypermethylation. The incomplete overlap between CIMP, MLH1 hypermethylation, and microsatellite instability indicates that these related “methylation phenotypes” may not be similar and should be investigated separately. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3086–96)
Data from Melanocytic Nevi, Nevus Genes, and Melanoma Risk in a Large Case-Control Study in the United Kingdom
Authors: Newton-Bishop Julia A. , Chang Yu-Mei , Iles Mark M. , Taylor John C. , Bakker Bert , Chan May , Leake Susan , Karpavicius Birute , Haynes Sue , Fitzgibbon Elaine , Elliott Faye , Kanetsky Peter A. , Harland Mark , Barrett Jennifer H. , Bishop D. Timothy
Published: March 2023

Abstract
Background: Increased number of melanocytic nevi is a potent melanoma risk factor. We have carried out a large population-based case-control study to explore the environmental and genetic determinants of nevi and the relationship with melanoma risk.

Methods: We report nevus phenotype in relation to differing patterns of sun exposure, inherited variation at loci shown in recent genome-wide association studies to be nevus genes, and risk.

Results: Increased numbers of nevi were associated with holiday sun exposure, particularly on intermittently sun-exposed body sites (test for Ptrend < 0.0001). Large nevi were also associated with holiday sun exposure (P = 0.002). Single nucleotide polymorphisms (SNP) on chromosomes 9 and 22 were associated with increased numbers of nevi (P = 0.04 and P = 0.002 respectively) and larger nevi (P = 0.03 and P = 0.002), whereas that on chromosome 6 was associated only with large nevi (P = 0.01). Melanoma risk was associated with increased nevus count, large nevi, and atypical nevi for tumors in all body sites (including rare sites) irrespective of age. The risk persisted when adjusted for inheritance of nevus SNPs.

Conclusions: The at-risk nevus phenotype is associated with behaviors known to increase melanoma risk (holiday sun exposure). Although SNPs on chromosomes 6, 9, and 22 were shown to be nevus genes, they explained only a small proportion of melanoma risk and nevus phenotype; therefore, several nevus genes likely remain to be identified.

Impact: This article confirms the importance of nevi in melanoma pathogenesis and increases understanding of their genetic determinants. Cancer Epidemiol Biomarkers Prev; 19(8); 2043–54. ©2010 AACR.
Data from Circulating Markers of Interstitial Lung Disease and Subsequent Risk of Lung Cancer
Authors: Shiels Meredith S. , Chaturvedi Anil K. , Katki Hormuzd A. , Gochuico Bernadette R. , Caporaso Neil E. , Engels Eric A.
Published: March 2023

Abstract
Background: Inflammation and pulmonary diseases, including interstitial lung diseases, are associated with increased lung cancer risk. Circulating levels of surfactant protein-D (SP-D) and Krebs von Lungren-6 (KL-6) are elevated in interstitial lung disease patients and may be useful markers of processes contributing to lung cancer.

Methods: We conducted a nested case–control study, including 532 lung cancer cases, 582 matched controls, and 150 additional controls with chest X-ray (CXR) evidence of pulmonary scarring, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serum SP-D and KL-6 levels were measured using enzyme immunoassay. Logistic regression was used to estimate the associations of SP-D and KL-6 with lung cancer and CXR scarring.

Results: Cases had higher levels than controls for SP-D (median 118.7 vs. 105.4 ng/mL, P = 0.008) and KL-6 (372.0 vs. 325.8 μg/mL, P = 0.001). Lung cancer risk increased with SP-D (Ptrend = 0.0003) and KL-6 levels (Ptrend = 0.005). Compared with the lowest quartile, lung cancer risk was elevated among those with the highest quartiles of SP-D (OR = 1.87, 95% CI: 1.32–2.64) or KL-6 (OR = 1.58, 95% CI: 1.11–2.25). Among controls, participants with CXR scarring were more likely than those without scarring to have elevated levels of SP-D (quartile 4 vs. quartile 1: OR = 1.67, 95% CI: 1.04–2.70, Ptrend = 0.05) but not of KL-6 (OR = 1.04, 95% CI: 0.64–1.68, Ptrend = 0.99).

Conclusion: Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk.

Impact: Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed. Cancer Epidemiol Biomarkers Prev; 20(10); 2262–72. ©2011 AACR.
Data from Accuracy of Self-Reported Nevus and Pigmentation Phenotype Compared with Clinical Assessment in a Population-Based Study of Young Australian Adults
Authors: Cust Anne E. , Pickles Kristen M. , Goumas Chris , Vu Thao , Schmid Helen , Nagore Eduardo , Kelly John , Aitken Joanne F. , Giles Graham G. , Hopper John L. , Jenkins Mark A. , Mann Graham J.
Published: March 2023

Abstract
Background: Awareness of individual risk may encourage improved prevention and early detection of melanoma.

Methods: We evaluated the accuracy of self-reported pigmentation and nevus phenotype compared with clinical assessment, and examined agreement between nevus counts from selected anatomical regions. The sample included 456 cases with invasive cutaneous melanoma diagnosed between ages 18 to 39 years and 538 controls from the population-based Australian Melanoma Family Study. Participants completed a questionnaire about their pigmentation and nevus phenotype, and attended a dermatologic skin examination.

Results: There was strong agreement between self-reported and clinical assessment of eye color [κ, = 0.78; 95% confidence interval (CI), 0.74–0.81]; and moderate agreement for hair color (κ = 0.46; 95% CI, 0.42–0.50). Agreement between self-reported skin color and spectrophotometer-derived measurements was poor (κ = 0.12; 95% CI, 0.08–0.16) to moderate (Spearman correlation rs = −0.37; 95% CI, −0.32 to −0.42). Participants tended to underestimate their nevus counts and pigmentation; men were more likely to underreport their skin color. The rs was 0.43 (95% CI, 0.38–0.49) comparing clinical total body nevus counts with self-reported nevus categories. There was good agreement between total body nevus counts and site-specific nevus counts, particularly on both arms.

Conclusions: Young adults have suboptimal accuracy when assessing important risk characteristics including nevus numbers and pigmentation. Measuring nevus count on the arms is a good predictor of full body nevus count.

Impact: These results have implications for the likely success of targeted public health programs that rely on self-assessment of these factors. Cancer Epidemiol Biomarkers Prev; 24(4); 736–43. ©2015 AACR.