bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2547: Targeted sequencing of 5p15 locus defined by non-small cell lung cancer (NSCLC) GWAS using next-generation sequencing.
Authors: Wang Zhaoxi , Zhao Yang , Su Li , Lee Seunggeun , Lin Xihong , Christiani David C. 
Published: August 2014

Abstract
Recent genome-wide association studies (GWAS) have identified genetic loci associated with lung cancer risk. Direct sequencing is regarded as the ultimate approach for moving beyond genetic mapping to identify causal mutations and define disease candidate genes. We conducted a pilot next-generation sequencing (NGS) of all exons of TERT and CLPTM1L genes within the 5p15 locus from our NSCLC GWAS, replicating previous studies. We performed an amplicon capture-NGS on 138 samples, including 82 NSCLC cases and 56 controls. These results were highly consistent across samples, with the majority covering 85-95% of bases at 100-fold and with only 5 samples failing to achieve 100-fold coverage for at least 80% of bases. We identified 11 SNPs in TERT and 5 SNPs in CLPTM1L. Using our SKAT/SKAT-O method, we found that both genes were associated with NSCLC (TERT, p=0.006; and CLPTM1L, p=0.04). When the SNPs of the two genes were combined, we saw a greater joint effect (p=0.001). In a subgroup analysis focusing on functional SNPs, including 7 and 4 nonsynonymous SNPs in TERT and CLPTM1L, respectively, we found a stronger association with TERT (p=0.0005), as well as an increased joint effect (p=0.0001). Moreover, none of the sequenced subjects had functional SNPs in both TERT and CLPTM1L genes. Furthermore, most nonsynonymous variations seemed clustered either in the cases or in the controls. Bioinformatic annotation of these nonsynonymous SNPs revealed that those clustered in the controls had only benign effects on the encoded protein, whereas those overrepresented in the NSCLC cases had possible damage to the encoded protein. Using Sanger dideoxy-terminator sequencing at an independent core facility and Taqman genotyping, all of the 11 functional SNPs identified by amplicon capture-NGS were confirmed. In summary, the results seem to support the hypotheses that aggregated functional variations, but not the neutral ones, contribute to the risks of NSCLC development. However, the initial finding is not conclusive, as this pilot project was limited by a small sample set and structural variations were not examined.
Citation Format: Zhaoxi Wang, Yang Zhao, Li Su, Seunggeun Lee, Xihong Lin, David C. Christiani. Targeted sequencing of 5p15 locus defined by non-small cell lung cancer (NSCLC) GWAS using next-generation sequencing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2547. doi:10.1158/1538-7445.AM2013-2547
Abstract 2560: MicroRNA target site polymorphisms and colorectal cancer risk in the Ashkenazi Jewish population.
Authors: Stenzel Stephanie L. , Gollub Jeremy , Shapero Michael , Finn Andrea , Rennert Gad , Gruber Stephen B. 
Published: August 2014

Abstract
MicroRNAs (miRNAs) act as key post-transcriptional regulators of gene expression via binding to the 3’ untranslated regions (UTRs) of mRNAs. Single nucleotide polymorphisms (SNPs) found in the miRNA sequence and/or corresponding binding sites can affect the fidelity of this interaction, and evidence from candidate miRNA studies suggests that such SNPs may increase or decrease risk of tumor development. This study was designed to expand the search for miRNA-related polymorphisms important in cancer etiology across the genome and to investigate the association between thousands of genetic variants in miRNA target sites and colorectal cancer (CRC) risk using a novel genotyping platform, the Axiom® miRNA Target Site Genotyping Array (237,858 markers). The final study sample after quality control filtering included 605 cases and 615 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study of incident CRC cases in a geographically-defined area of northern Israel. The marginal association between each marker with minor allele frequency &gt;=1% and CRC risk was examined assuming a log-additive genetic model using logistic regression adjusted for sex, age, and the first two principal components (PC) to capture fine-scale population structure. There were 11 markers with p-values less than 3E-4, and the most statistically significant association involved rs12130051 (chr1:19545053; 3’-UTR of KIAA0090) with an OR of 2.24 (1.52,3.31) and p=4.48E-5. In addition, rs1051690 (chr5:142605172; 3’-UTR of ARHGAP26), was statistically significantly associated with decreased CRC risk (OR (95% CI): 0.71 (0.59, 0.85); p = 2.03E-4). Further, this study provided evidence for replication of a previously published locus, rs1051690 in the 3’UTR region of the insulin receptor gene, INSR (OR (95% CI): 1.27 (0.96,1.67); p = 0.09). A fixed-effects meta-analysis of sample-size weighted p-values from a recent publication in Carcinogenesis describing the INSR variant (Landi et al., 2012) and from the current MECC study yielded a combined p-value of 0.01. To our knowledge, this is the first study to examine the association between genetic variation in miRNA target sites and cancer risk using a genome-wide approach. Work is ongoing to replicate findings from this study and to characterize the functional impact of prioritized polymorphisms.
Citation Format: Stephanie L. Stenzel, Jeremy Gollub, Michael Shapero, Andrea Finn, Gad Rennert, Stephen B. Gruber. MicroRNA target site polymorphisms and colorectal cancer risk in the Ashkenazi Jewish population. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2560. doi:10.1158/1538-7445.AM2013-2560
Abstract 2571: Genetic variations in telomere maintenance pathway genes are associated with risk of esophageal cancer.
Authors: Ye Yuanqing , Ajani Jaffer , Wu Xifeng 
Published: August 2014

Abstract
Many studies have shown the association of telomere dysfunction with aging and cancer development. We hypothesize that genetic variations in telomere maintenance genes may modulate esophageal cancer risk. To test this hypothesis, we comprehensively assessed the association of 616 SNPs in 45 telomere maintenance pathway genes in 602 esophageal adenocarcinoma cases and 1,512 healthy controls. Unconditional multivariate logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) while adjusting for age, gender, and smoking status. In single SNP analysis, a total of 77 SNPs had P value &lt; 0.05. 5 SNPs remained significant after adjusting for multiple comparisons at FDR &lt; 0.10 including 3 SNPs in PINX1 gene and 2 SNPs in TPP1 gene. The most significant association was observed for rs9657541 in PINX1 gene that exhibited a significantly reduced risk of esophageal cancer in dominant model (OR = 0.62, 95% CI = 0.50-0.77, P = 1.54×10−5, FDR = 0.020). Cumulative effects of SNPs were assessed by the number of unfavorable genotypes. Each subject was classified into low (zero unfavorable genotype), medium (one to three unfavorable genotypes), and high-risk groups (more than three unfavorable genotypes). Compared with the low-risk group, the OR was 1.58 (95% CI = 1.20-2.09) for the median-risk group and 2.57 (95% CI = 1.87-3.54) for the high-risk group. Classification and regression tree (CART) analysis was performed to identify genetic profiles that can classify individuals into differential risk of esophageal cancer. CART analysis identified 3 terminal nodes. Compared to terminal node 1, individuals in terminal nodes 2 and 3 had significantly increased risks of esophageal cancer with ORs of 1.43 (95% CI = 1.13-1.80) and 2.46 (95% CI = 1.81-3.34), respectively. We also performed gene-based analysis to determine the combined effect of SNPs within a gene region and identified four genes (TPP1, PINX1, TNKS, TERF1) significantly associated with the risk of esophageal cancer. In conclusion, our results suggest that genetic variants in telomere maintenance pathway genes may contribute to the altered risk of esophageal cancer, both individually and jointly.
Citation Format: Yuanqing Ye, Jaffer Ajani, Xifeng Wu. Genetic variations in telomere maintenance pathway genes are associated with risk of esophageal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2571. doi:10.1158/1538-7445.AM2013-2571
Abstract 2572: Vitamin D intake and lung cancer risk in the Women's Health Initiative (WHI).
Authors: Cheng Ting-Yuan David , LaCroix Andrea Z. , Beresford Shirley A.A. , Goodman Gary E. , Thornquist Mark D. , Zheng Yingye , Chlebowski Rowan T. , Ho Gloria Y.F. , Neuhouser Marian L. 
Published: August 2014

Abstract
Background: Prior research suggests that vitamin D protects against lung cancer with evidence only among subgroups including women and non-smokers. We investigated whether vitamin D intake was associated with lung cancer and explored whether vitamin A intake modified the association.
Methods: Data from 128,779 postmenopausal women including 1,771 incident lung cancers in the Women's Health Initiative, 1993-2010, were analyzed. Twelve percent of women received active intervention (1 g calcium+400 IU vitamin D3 daily) in the Calcium/Vitamin D Trial. Baseline total intake was assessed by a food frequency questionnaire and supplement bottle labels. Hazard ratios (HR) were estimated by Cox proportional hazard models.
Results: No association was observed overall. Among never smokers, vitamin D intake was inversely associated with total lung cancer (HR=0.37, 95% confidence interval [CI]=0.18-0.77, ≥800 vs. &lt;100 IU/d; P-trend=0.01). The Calcium/Vitamin D Trial active intervention was not associated with a lower lung cancer risk among women with vitamin A intake ≥1,000 μg/d Retinol Activity Equivalent (RAE), but among those with vitamin A intake &lt;1,000 μg/d RAE (HR=0.69, 95% CI=0.50-0.96; P-interaction=0.09). Among current smokers with excess vitamin A intake (≥3,000 μg/d RAE), the intervention was associated with a higher lung cancer risk (HR=2.26, 95% CI=1.02-5.01), as no association was observed among current smokers with vitamin A intake &lt;3,000 μg/d RAE (P-interaction=0.01).
Conclusion: Vitamin D intake was associated with a lower lung cancer risk in never-smoking, postmenopausal women. Lower vitamin A intake may be important for a beneficial association of 1 g calcium+400 IU vitamin D3 supplementation with lung cancer.
Citation Format: Ting-Yuan David Cheng, Andrea Z. LaCroix, Shirley A.A. Beresford, Gary E. Goodman, Mark D. Thornquist, Yingye Zheng, Rowan T. Chlebowski, Gloria Y.F. Ho, Marian L. Neuhouser. Vitamin D intake and lung cancer risk in the Women's Health Initiative (WHI). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2572. doi:10.1158/1538-7445.AM2013-2572
Abstract 2573: Serum proteomic analysis of early pregnancy-induced protection against breast cancer.
Authors: Gutierrez Christina , Arumugam Arunkumar , Lopez Rebecca , Boopalan Thiyagarajan , Nandy Sushmita , Agullo Pamela , Parada Jacqueline , Love Susan , Lakshmanaswamy Rajkumar 
Published: August 2014

Abstract
The incidence of breast cancer is very high in western countries and is increasing rapidly in the third world. It is the most common cancer in women worldwide. Since it is difficult to defeat breast cancer after it has occurred, finding new strategies to delay or prevent the development of breast cancer has been an important area for clinical and experimental investigations. Women who undergo a full- term pregnancy before the age of 20, with or without lactation, have about one half the risk of developing breast cancer compared to women who undergo their first pregnancy after the age of 35 or women who have never undergone a full term pregnancy. This universal protective effect of pregnancy serves as a major clue and starting point in the search for new strategies and novel biomarkers related to the prevention of breast cancer. For the current study, women were recruited into one of the following categories; 1) had their first child ≤ 25 years of age [early parous], 2) had their first child ≥ 35 years of age [late parous], and 3) a control group of women the same age as those in groups 1 and 2 but who have never given birth [nulli parous]. Blood was collected these women and serum was separated. A high throughput proteomic analysis was performed with the samples collected. Briefly, protein was extracted from the samples and conjugated to a phosphoexplorer antibody array, detected with Cy3- streptavidin, and scanned with a microarray scanner. Using bioinformatic software, significantly differentially expressed proteins of interest have been found in late parous and nulli parous samples when compared to the early parous samples. We have identified the top 20 differentially expressed total (LIMK1, p53, Paxillin, Ret, Tyrosine hydroxylase) and phosphorylated (p14-3-3 theta, p14-3-3 zeta, pCav1, pCD3Z, pDok-1) proteins between the different groups. Several proteins identified using the phosphoexplorer antibody arrays have been validated using Western blots. Overall, this study focuses on the analysis of human breast tissue and serum to gain a deeper understanding of how early parity confers protection against breast cancer.
Citation Format: Christina Gutierrez, Arunkumar Arumugam, Rebecca Lopez, Thiyagarajan Boopalan, Sushmita Nandy, Pamela Agullo, Jacqueline Parada, Susan Love, Rajkumar Lakshmanaswamy. Serum proteomic analysis of early pregnancy-induced protection against breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2573. doi:10.1158/1538-7445.AM2013-2573
Abstract 2576: Novel resveratrol analog ARSHA shows higher potency for inhibiting the growth of triple negative breast cancer cells.
Authors: Chatterjee Anwesha , Ronghe Amruta M. , Singh Bhupendra , Padhye Subhash B. , Bhat Hari K. 
Published: August 2014

Abstract
Resveratrol (Res) (3, 5,
4’-trihydroxystilbene) is a well known naturally occurring polyphenol that exhibits anti-tumor activity. However, its poor bioavailability and rapid metabolism limits its use as a preferred anticancer agent. In an attempt to improve the bioavailability and anticancer potential of Res, we have synthesized five new Res analogs. We then tested the ability of these analogs to inhibit the proliferation of 5 breast cancer cell lines and 3 non-neoplastic breast epithelial cell lines and compared their inhibition potential with
Res. MTT assay for cell proliferation was carried out in human breast cancer and non-neoplastic breast epithelial cell lines. The breast cancer cell lines tested were MCF-7, T47D, MDA-MB-231,
MDA-MB-468 and BT-20. The non-neoplastic breast cell lines tested were MCF-10A,
MCF-10F and HMLE. Of all the analogs tested, one namely ARSHA showed higher potency for inhibiting the proliferation of breast cancer cells compared to
Res. Furthermore, ARSHA showed higher potency for inhibiting the growth of triple negative breast cancer cells (MDA-MB-231, MDA-MB-468 and BT-20) compared to estrogen receptor positive breast cancer cells MCF-7 and T47D. There was neither inhibition nor proliferation by ARSHA of non-neoplastic breast epithelial cell lines tested when compared to vehicle-treated controls.
ARSHA induced Beclin-1 and LC3II which suggest autophagy mediated inhibition of cell growth. Beclin-1 is known to be suppressed in breast cancers and it's over expression is reported to inhibit breast cancer. Results from our studies demonstrate that Res-analog ARSHA is better than Res in inhibiting specifically breast cancer cell growth and shows higher potency for inhibiting the growth of triple negative breast cancer cells by inducing autophagy with an earlier onset for triple negative breast cancer cells. Therefore, ARSHA may be a better chemotherapeutic agent than Res against breast cancer and more specifically against triple negative breast cancer cell growth, a cancer type prevalent in minority African American population with poor prognosis.
Citation Format: Anwesha Chatterjee, Amruta M. Ronghe, Bhupendra Singh, Subhash B. Padhye, Hari K. Bhat. Novel resveratrol analog ARSHA shows higher potency for inhibiting the growth of triple negative breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2576. doi:10.1158/1538-7445.AM2013-2576
Abstract 2577: ARSHA, a novel analog of resveratrol inhibits proliferation of breast cancer cells by modulating expressions of ERα and ERβ.
Authors: Ronghe Amruta M. , Chatterjee Anwesha , Singh Bhupendra , Padhye Subhash B. , Bhat Hari K. 
Published: August 2014

Abstract
Epidemiologic evidence suggests that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Resveratrol, a bioflavonoid found naturally in grapes, has been very effective as an antiproliferative agent in vitro. However, its poor bioavailability and rapid metabolism limits its use as a preferred anticancer agent.
The problem of poor bioavailability of resveratrol can be solved by the synthesis of its analogs with appropriate chemical modifications that would enhance the stability and anticancer potency of resveratrol. To achieve this objective, we have synthesized a library of resveratrol analogs that resemble the basic skeleton of resveratrol but have structural modifications. These novel analogs were screened for their potential to inhibit growth of breast cancer cells. One analog, namely, ARSHA showed better potential and selectivity in inhibiting the proliferation of breast cancer cells.
Our next goal was to identify the mechanism by which ARSHA specifically inhibits the growth of breast cancer cells. Estrogen receptor (ER) expressing cell lines MCF-7 and T47D, and ER negative cell line MDA-MB-231 as well as ERβ-transfected cell line MDA-MB-231 were treated with 50μM doses of ARSHA for upto 72 hours. mRNA and protein was isolated from respective cell lines. Real-time PCR and western blot analyses were performed. ARSHA significantly induced the expression of ERβ (∼3-fold) and inhibited the expression of ERα (0.2-fold) compared to vehicle treated controls. Taken together, our findings indicate that novel resveratrol analog ARSHA may inhibit the proliferation of breast cancer cell lines by inhibiting the expression of ERα and inducing the expression of ERβ. Estrogen receptor α acts as a mediator of proliferation while ERβ acts as an inhibitor of estrogen signaling.
Citation Format: Amruta M. Ronghe, Anwesha Chatterjee, Bhupendra Singh, Subhash B. Padhye, Hari K. Bhat. ARSHA, a novel analog of resveratrol inhibits proliferation of breast cancer cells by modulating expressions of ERα and ERβ. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2577. doi:10.1158/1538-7445.AM2013-2577
Abstract 2582: In vitro effects of 4-OXO-docosahexaenoic ester on cell signaling in molecular subtypes of human breast cancer cell lines.
Authors: Thompson Henry J. , Jiang Weiqin , Zhu Zongjian , Vanden Heuvel John P. , Amin Shantu , Gowda Krishne , Manni Andrea , El-Bayoumy Karam 
Published: August 2014

Abstract
In vivo preclinical evidence of a heterogeneous effect of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of mammary carcinomas (Cancer Res. 2012 Aug 1;72(15):3795-806) is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of breast cancer. Similarly, available evidence indicates that specific metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite specific biological activities. To begin to unravel the complex relationships among molecular subtype specific cell signaling and effects exerted by specific N3FA metabolites on those pathways, a series of proof-in-concept experiments were conducted using cell lines representing 5 molecular subtypes of human breast cancer (BT-474, MCF-7, SKBR-3, MDA-MB-231, MDA-MB-468) and 4-oxo-docosahexaenoic keto ester (4-oxo-DHA), a putative metabolite of docosahexaneoic acid (DHA) that has superior activity to that of DHA in inducing PPARγ activation in vitro. 4-oxo-DHA induced dose dependent inhibition of cell number accumulation of all molecular subtypes but the dose and time responses varied markedly with MCF-7 cells being the least affected and MDA-MB-468 being inhibited to the greatest extent. Detailed mechanistic studies in BT-474, SKBR-3, and MDAMB-463 revealed subtype specific patterns of cell cycle inhibition and apoptosis induction with apoptosis induction dominating in BT-474 and SKBR-3 and inhibition of cell proliferation and apoptosis induction accounting for growth inhibition of MDA-MB-468. While some molecular subtypes were inhibited by mechanisms involving PPARγ activation, others underwent cell growth inhibition via modulation of multiple regulatory nodes in the mTOR signaling network. Evidence is consistent with differential sensitivity among cell types based on whether they are basal or luminal in origin. The experiments described offer a useful complementary approach to the in vivo experiments needed to resolve the N3FA-breast cancer conundrum.
This work was supported by grant KG081632 from the Susan G. Komen Foundation.
Citation Format: Henry J. Thompson, Weiqin Jiang, Zongjian Zhu, John P. Vanden Heuvel, Shantu Amin, Krishne Gowda, Andrea Manni, Karam El-Bayoumy. In vitro effects of 4-OXO-docosahexaenoic ester on cell signaling in molecular subtypes of human breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2582. doi:10.1158/1538-7445.AM2013-2582