bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 30: The epidemiology of triple-negative breast cancer: A review.
Authors: McCullough Lauren E. , Family Leila , O'Brien Katie M. , Razzaghi Hilda , Backes Danielle M. , Mordukhovich Irina , Reiter Paul L. , Olshan Andrew F. 
Published: August 2013

Abstract
Background: Molecular profiling of breast tumors has enhanced our knowledge of the heterogeneity of breast cancer, including the identification of subtypes associated with differences in prognosis. However, the etiology of these intrinsic subtypes remains unknown. The triple-negative subtype accounts for 10-25% of breast tumors and is most common among African-American and premenopausal women. The purpose of this review was to summarize the existing literature on the risk factors for triple-negative disease.
Methods: Epidemiologic studies published between January 2000 and December 2011 that reported subtype-specific effect measure estimates for hormonal and other breast cancer risk factors in case-only or case-control analyses were included. A total of 20 studies from 17 populations met our pre-specified inclusion criteria.
Results: Compared to luminal A, triple-negative cases were more likely to have younger age at menarche, higher parity, shorter duration of breastfeeding, and increased premenopausal body mass. Case-control data suggest that there may be positive associations between parity, premenopausal body mass and risk of triple-negative disease, while inverse associations were observed for age at first term full-term pregnancy.
Conclusions: Our review confirms that risk factor profiles may vary by subtype; although we were unable to draw definitive conclusions regarding all hormonal risk factors and risk of triple-negative disease.
Impact: Because this subtype represents a small proportion of tumors, collaborative efforts should be undertaken to precisely evaluate potential associations. In addition, future investigations should focus on enrolling a greater number of African-American participants, as this population is underrepresented in the majority of current studies.
Citation Format: Lauren E. McCullough, Leila Family, Katie M. O'Brien, Hilda Razzaghi, Danielle M. Backes, Irina Mordukhovich, Paul L. Reiter, Andrew F. Olshan. The epidemiology of triple-negative breast cancer: A review. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 30.
Abstract 39: Exposure to heavy metals and polycyclic aromatic hydrocarbons and DNA damage in Taiwanese traffic conductors.
Authors: Huang Han-Bin , Chen Guan-Wen , Wang Chien-Jen , Lin Yong-Yang , Liou Saou-Hsing , Lai Ching-Huang , Wang Shu-Li 
Published: August 2013

Abstract
Introduction: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) and heavy metals, has been associated with the etiology and prognosis of many illnesses. However, the specific causal agents and underlying mechanisms for different health outcomes remain unclear. The aims of this study were to assess the relations between urinary biomarkers of exposure to PAHs (1-hydroxypyrene-glucuronide, 1-OHPG) and heavy metals (cadmium, Cd; nickel, Ni; arsenic, As; lead, Pb; copper, Cu) and their interaction effect on DNA damage (8-oxo-7,8-dihydro-guanine, 8-oxodG).
Methods: We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei, Taiwan. Post-shift urine samples from 2 consecutive days were analyzed for 1-OHPG, Cd, Ni, As, Pb, Cu and 8-oxodG. To estimate the effects from PAHs and metals on DNA damage, we constructed a linear mixed model adjusted for confounding variables.
Results: We found that urinary 1-OHPG and Cd levels were independent predictors of urinary 8-oxodG levels (β=0.112, p=0.015 for 1-OHPG; β=0.138, p=0.031 for urinary Cd). The joint effect of urinary 1-OHPG and Cd levels was associated with urinary 8-oxodG levels (p=0.001).
Conclusions: Co-exposure to environmental PAHs and Cd could cause oxidative DNA damage. These findings suggest that the additive interaction between exposure to environmental PAHs and Cd could enhance the burden of oxidative stress.
Citation Format: Han-Bin Huang, Guan-Wen Chen, Chien-Jen Wang, Yong-Yang Lin, Saou-Hsing Liou, Ching-Huang Lai, Shu-Li Wang. Exposure to heavy metals and polycyclic aromatic hydrocarbons and DNA damage in Taiwanese traffic conductors. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 39.
Abstract 69: Blood leukocyte DNA methylation and colorectal cancer among male smokers in Finland.
Authors: Gao Ying , Paul Meltzer , Caporaso Neil 
Published: August 2013

Abstract
Aim: To explore the association between methylation in leukocyte DNA and colorectal cancer (CRC) risk in male smokers using the α-tocopherol, β-carotene cancer prevention study.
Methods: About 221 incident CRC cases, and 219 controls, frequency-matched on age and smoking intensity were included. DNA methylation of 1505 CpG sites selected from 807 genes were evaluated using Illumina GoldenGate Methylation Cancer Panel I in pre-diagnostic blood leukocytes of study subjects. Tertiles of methylation level classified according to the distribution in controls for each CpG site were used to analyze the association between methylation level and CRC risk with logistic regression. The time between blood draw to cancer diagnosis (classifying cases according to latency) was incorporated in further analyses using proportional odds regression.
Results: We found that methylation changes of 31 CpG sites were associated with CRC risk at P &lt; 0.01 level. Though none of these 31 sites remained statistically significant after Bonferroni correction, the most statistically significant CpG site associated with CRC risk achieved a P value of 1.0 × 10(-4). The CpG site is located in DSP gene, and the risk estimate was 1.52 (95% CI: 0.91-2.53) and 2.62 (95% CI: 1.65-4.17) for the second and third tertile comparing with the lowest tertile respectively. Taking the latency information into account strengthened some associations, suggesting that the methylation levels of corresponding sites might change over time with tumor progression.
Conclusion: The results suggest that the methylation level of some genes were associated with cancer susceptibility and some were related to tumor development over time. Further studies are warranted to confirm and refine our results.
Citation Format: Ying Gao, Paul Meltzer, Neil Caporaso. Blood leukocyte DNA methylation and colorectal cancer among male smokers in Finland. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 69.
Abstract 73: Evaluation of bead-based assays of inflammation markers for epidemiologic studies.
Authors: Poole Elizabeth M. , Townsend Mary K. , Eliassen A Heather , Neville-Golden Janine , Tworoger Shelley S. 
Published: August 2013

Abstract
Given finite sample availability in epidemiologic studies, minimizing assay volumes is an important consideration in studies of biomarker-disease relationships. Consequently, there is great interest in multiplex assays that use less volume than standard assays and provide data on multiple markers in one assay. This is particularly true for markers of inflammation, a key factor in cancer and other age-related diseases. Therefore, we conducted pilot studies of three bead-based, multiplex, inflammatory marker panels at three laboratories. The first pilot evaluated assay reproducibility by calculating the coefficient of variation (CV) using 12 blinded replicate samples, and the second evaluated the role of delayed processing using samples from 12 participants who had one-third of their sample processed immediately after blood draw, and one-third each processed 24 and 48 hours later. Minimum criteria for an analyte to pass the pilots were: (1) &gt;50% of samples had levels above the limit of detection (LOD), (2) a CV ≤20%, and (3) an intraclass correlation across processing times &gt;0.80. For Panel 1, 200uL of plasma was used to assess 10 biomarkers in 2007. For Panel 2, 50uL of plasma was used to assess 17 markers in 2011. For Panel 3, 250uL of plasma was used to assess 12 markers in 2012. More than half of the biomarkers in two of the panels (1 and 3) had &gt;50% of samples with levels less than the LOD; in Panel 2 29% of biomarkers had &gt;50% of samples below the LOD. Of the biomarkers with more than half the samples above the LOD, all had CVs &lt;20%. Overall, 3 (30%) of markers passed the LOD and CV criteria in Panel 1, 12 (71%) passed in Panel 2, and 4 (33%) passed in Panel 3. Among these, none of the markers in Panels 1 and 3 and 7 markers in Panel 2 were stable with delayed processing, resulting in an overall pass rate of 0% in Panels 1 and 3 and 41% in Panel 2. Further, for Panel 2, we observed that the correlation between the multiplex and the standard ELISA for IL-6 was only 0.25. Our results suggest that assessing inflammatory markers on bead-based multiplex platforms may not be appropriate for epidemiologic studies, possibly reflecting poor assay optimization for specific biomarkers and thus lowered overall assay sensitivity and specificity.
Citation Format: Elizabeth M. Poole, Mary K. Townsend, A Heather Eliassen, Janine Neville-Golden, Shelley S. Tworoger. Evaluation of bead-based assays of inflammation markers for epidemiologic studies. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 73.
Abstract 77: Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women.
Authors: Bauer Scott R. , Fortner Renee T. , Gates Margaret A. , Eliassen Heather , Hankinson Susan E. , Tworoger Shelley S. 
Published: August 2013

Abstract
The use of common analgesics, such as aspirin, non-aspirin NSAIDs and acetaminophen, may be associated with the risk of several hormone-related cancers, possibly via effects on sex hormone and prolactin concentrations. Therefore, we assessed the cross-sectional relationship between analgesic (aspirin, non-aspirin NSAIDS, and acetaminophen) use and sex hormone and prolactin concentrations among 2,034 premenopausal women, 32 to 54 years old, from the Nurses' Health Study II. Approximately 84% of women provided timed luteal and follicular blood samples; the remainder provided a single untimed sample. After adjustment for age, BMI, parity, and other potential confounders, acetaminophen use was inversely associated with prolactin levels (ptrend= 0.04). Compared to non-users, prolactin concentrations were 11.8% lower among women who reported using acetaminophen at least 2 times per week (p&lt;0.01). Similarly, acetaminophen was inversely associated with free testosterone, when comparing use at least 2 times per week to non-users (7.1% lower, p = 0.04; ptrend= 0.04). Use of non-aspirin NSAIDs was positively associated with follicular free estradiol, with 13.5% higher levels in women who reported use 4 or more days per week as compared to non-users (p = 0.04; ptrend= 0.11); results for free follicular estradiol were similar (13.2% higher, p = 0.06; ptrend= 0.11) though not statistically significant. There were no clear associations observed between analgesic use and luteal estradiol, estrone, estrone sulfate, DHEA, DHEAS, androstenedione, and estrogen/androgen ratios. After adjustment for multiple comparisons, none of the associations were statistically significant. In conclusion, our study provides modest evidence for an association of acetaminophen use with prolactin and free testosterone concentrations in premenopausal women, and the suggestion of an association between non-aspirin NSAIDs and follicular free estradiol among those with frequent use.
Citation Format: Scott R. Bauer, Renee T. Fortner, Margaret A. Gates, Heather Eliassen, Susan E. Hankinson, Shelley S. Tworoger. Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 77.
Abstract IA01: New assays, old specimens: Multiplexing for plasma and urine.
Authors: Sluss Patrick M. 
Published: August 2013

Abstract
A key concept in medical science is that by comparing DNA, RNA, or proteins from healthy and diseased individuals, insight can be gained into the etiology of disease leading to better diagnostics and therapeutics. In this context, biorepositories have long played a key role by allowing the accumulation of biological fluids and tissues from large numbers of individuals for longitudinal or cross-sectional comparisons. Approaches to understanding human disease are based on the central dogma that information flow in living systems is from DNA to RNA to protein. At all levels, aberrations could indicate either the presence of disease or suggest underlying mechanisms of disease. However, historically DNA and RNA have been more useful for identifying risk of disease than the presence of disease, except in surgical specimens. Proteins in biological fluids [blood, urine, aspirates, etc.] have played a more prominent role in diagnostics. Indeed given that proteins are in essence the effectors of gene expression a long held goal has been to associate specific proteins in peripheral circulation that indicate the presence of disease, e.g. biomarkers of disease, especially early disease before the appearance of symptoms or other clinical indicators.
This presentation will focus on issues associated with the use of biorepository fluids in this context. Three issues are fundamental: 1) specimen volume is limited and precious, 2) specimen processing requirements are not known a'priori, and 3) analytical targets are often not precisely defined. Limited specimen volume is an inherent problem because each blood draw represents a discrete end point. Unlike nucleic acids, proteins are subject to numerous post-translational biological modifications and to extensive, often rapid, degradation post specimen collection. These issues drive method development and validation, ultimately determining the amount and quality of data that can be obtained from biorepository specimens. Protein analytical methods will be reviewed from this perspective with emphasis on recent developments in multi-analyte systems and newer, highly sensitive methods.
Citation Format: Patrick M. Sluss. New assays, old specimens: Multiplexing for plasma and urine. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA01.
Abstract IA02: New specimens: Buccal cells, nasal swabs, fecal samples.
Authors: Cox David 
Published: August 2013

Abstract
Buccal swabs have been used for decades as an economical method to obtain biomaterials suitable for genomic DNA extraction for use in forensics and molecular epidemiology studies. Using buccal swabs, as opposed to methods such as saliva collection or rinsing with mouthwash, was considered sub-optimal as they contained large quantities of microbial DNA. As there is roughly an order of magnitude more non-human than human cells in our bodies, a large proportion of non-human DNA in many biospecimens is to be expected. While some bacteria are pathological, many carry out important functions or protect the body. The complex interactions between environmental factors, the human microbiome, and the human host can provide important clues with respect to various diseases and response to treatment. Advances in technology with respect to DNA sequencing allow for not only highly accurate determination of specific strains of bacteria but also the detection of very low proportions of those strains in biological samples. Similarly, advanced techniques such as mass spectroscopy provide information as to how changes in the microbiome and/or the host influence overall metabolism. These techniques have opened the door for a new wave of interest in the microbiome and its influence on metabolism and human health.
Citation Format: David Cox. New specimens: Buccal cells, nasal swabs, fecal samples. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA02.
Abstract IA04: Searching for GxE interactions in genome-wide association studies.
Authors: Conti David V. 
Published: August 2013

Abstract
Although both genetic and environmental factors play important roles in the etiology of many complex human traits, scans for gene(G)-environment(E) interaction have been mostly neglected in current GWAS. This is mainly due to the substantial lack of power for interaction tests coupled with the massive number of interactions available for testing. The conventional statistical approach for interactions, the case-control analysis, suffers from low power. The alternative case-only analysis can be more powerful but slight violations in the underlying assumption of independence can greatly bias the results. In this talk, I discuss several recently proposed alternatives ranging from two-step analyses to Bayesian approaches. Each approach attempts to leverage various aspects of the data, from ascertainment, to marginal test, to estimates of G-E association in the controls. For example, in the two-step approach proposed by Murcray et al. (2009), a preliminary screening step tests the association of G with E in the combined sample of cases and controls, thus capturing any G-E association that may be present in the study sample by leveraging the oversampling of cases from the population. This step is followed by a conventional case-control analysis. Overall, there is a substantial increase in power compared to a genome-wide scan of interactions due to the drastic reduction in the number of tests evaluated. In contrast, several Bayesian approaches (Mukherjee and Chatterjee, 2008; Li and Conti 2009) attempt to obtain an estimate of interaction that is a combined estimate between the case-only and case-control estimates. While originally conceived as an approach for a single GxE interaction test, I will discuss recent extensions leveraging the fact that most SNPs in a GWAS are not associated with either the outcome nor the environmental factor. For these and several other approaches, I will discuss the underlying assumptions and the sensitivity of the performance of each to G-E association in the population, population prevalence, and the assumed causal model.
Citation Format: David V. Conti. Searching for GxE interactions in genome-wide association studies. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA04.
Abstract IA06: Identification of tumor-associated cassette exons in human cancer through exon-array and RNA-Seq data analysis.
Authors: Valletti Alessio , Palumbo Orazio , D'Antonio Mattia , Castrignano' Tiziana , Gigante Margherita , Carella Massimo , Picardi Ernesto , Maria D'Erchia Anna , Elena Ranieri , Pesole Graziano 
Published: August 2013

Abstract
Many evidences report that alternative splicing, the mechanism producing mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumor biomarkers, as well as of new targets for more selective and effective therapies.
We developed novel and effective computational tools for performing a genome-wide analysis of the alternative splicing pattern of human genes using both exon array and RNA-Seq data. Notably, we sought to identify “cassette exon” generated by exon skipping differentially expressed in the tumor and normal conditions.
To this aim we analyzed data obtained by exon array hybridization from clear cell renal carcinoma (ccRC) and colorectal cancer (CRC) samples as well as from the corresponding normal controls. Furthermore, high-throughput transcriptome sequencing from CRC and control samples were also analyzed. By using our computational strategy we identified several cassette exons differentially expressed in the tumoral and normal conditions.
In order to test the effectiveness of our computational strategy, we experimentally verified the occurrence of tumor- and normal-specific cassette exons by RT-qPCR assay. Remarkably, we were able to confirm “in vivo” the differential expression of these predicted cassette exons in patients affected by CRC and ccRC.
This study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific candidate biomarkers for CRC and ccRC.
Citation Format: Alessio Valletti, Orazio Palumbo, Mattia D'Antonio, Tiziana Castrignano, Margherita Gigante, Massimo Carella, Ernesto Picardi, Anna Maria D'Erchia, Elena Ranieri, Graziano Pesole. Identification of tumor-associated cassette exons in human cancer through exon-array and RNA-Seq data analysis. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA06.