bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1208: Is the decrease in the incidence of large cell carcinoma of the lung due to changes in classification towards adenocarcinoma
Authors: Hashim Dana , Znaor Ariana , Travis William , Boffetta Paolo 
Published: August 2018

Abstract
Background: Data from many populations show a decrease in the incidence of large cell carcinoma (LCC) of the lung while incidence of lung adenocarcinoma (AC) is decreasing to a lower rate or even increasing from the 1990s. We compared the changes in incidence of lung LCC and AC worldwide to test the hypothesis that at least part of the decline in LCC incidence was due to classification of these tumors as AC.
Methods: We analyzed the annual percent change (APC) in the age-standardized rates (ASRs) of lung LCC and AC incidence between 1996 and 2007 in 78 high-quality cancer registries from Europe, Asia, North America, and South America, using linear regression.
Results: Among women, the median APC of LCC incidence was -5.42, and that of AC incidence was -0.96. There was a positive correlation between the two measures (β=0.29; p=0.01). The APC of LCC incidence was negative in 64 populations (82.1%); that of AC incidence was negative in 50 populations (63.3%, p of the χ2 distribution = 0.07). Among women, the median APC for LCC and AC incidence was -5.06 and +2.11, respectively. The correlation between the two measures was 0.17 (p=0.03). The APC of LCC incidence was negative in 59 populations (76.6%); that of AC incidence was negative in 23 populations (29.9%, p of the χ2 distribution = 0.41).
Conclusions: The decrease in LCC may be, in part, due to changes in histologic classification and triaging towards a diagnosis of adenocarcinoma.
Citation Format: Dana Hashim, Ariana Znaor, William Travis, Paolo Boffetta. Is the decrease in the incidence of large cell carcinoma of the lung due to changes in classification towards adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1208.
Abstract 1210: Trend in the incidence of gynecologic malignancies in Federal Teaching Hospital Abakaliki: A 5-year review
Authors: Agboeze Joseph , Onoh Robinson , Igwe Matthew 
Published: August 2018

Abstract
Background: Gynecological malignancies are common and are among the leading causes of cancer-related deaths worldwide Objective: To determine the trend in the incidence of gynaecological malignancies in Federal Teaching Hospital, Abakaliki, Nigeria.
Methods: This was a retrospective study. The study population was the patients diagnosed of gynaecological cancers at the Federal Teaching Hospital, Abakaliki between January, 2012 to December 2015. Data were extracted from case notes of patients, discharge books and the operating theatre record books. The data were analyzed using Epi Info version 7.1.4 and the results expressed in descriptive statistics by simple percentages.
Results: There were 2528 gynaecological admissions during the period. There were 97 women who had genital tract malignancies giving an incidence of 3.8% of gynaecological admissions. Cervical cancer was the most common female genital tract malignancy occurring in 68% of gynaecological cancers, followed by ovarian cancer (11.3%), Endometrial cancer (8.3%), Vulva cancer (6.2%),Choriocarcinoma (4.1%), and the least was leiomyosarcoma (1.0%). The mean age was 54.2 ±11.9 years.The incidences of cervical, ovarian vulva and endometrial cancers showed a steady increase over the period. Choriocarcinoma did not show a significant change in incidence.
Conclusion: This study showed the rising incidences of gynaecological cancers. Cancer of the cervix is the commonest gynaecological malignancy and most patients presented late. Cervical cancer screening programmes, early detection and awareness campaign is highly recommended.
Citation Format: Joseph Agboeze, Robinson Onoh, Matthew Igwe. Trend in the incidence of gynecologic malignancies in Federal Teaching Hospital Abakaliki: A 5-year review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1210.
Abstract 1212: Urinary bladder cancer in Sokoto, Northwestern Nigeria: A 10-year histopathological review
Authors: Sahabi Saddiku Malami , Abdullahi Kabiru 
Published: August 2018

Abstract
Background: Urinary Bladder Cancer is a common disease worldwide. It ranks ninth in cancer incidence and is the 13th leading cause of cancer death among men and women worldwide. The highest incidence is seen usually in developed countries. In our environment, it is the leading cause of cancer and cancer deaths among males because of endemicity of urinary schistosomiasis. Yet, little is done to curb this preventable risk factor of bladder cancer.
Objective: The objectives of this study were to describe histopathological pattern of urinary bladder cancer in Sokoto, Northwestern Nigeria.
Method: This was a retrospective study of all histologically confirmed cases of bladder cancer seen at the Department of Histopathology, Usmanu Danfodiyo University Teaching Hospital, Sokoto between the years 2006 and 2015. Information was obtained from the database of the Department of Histopathology. The data were validated using Microsoft Excel and exported to SPSS for analysis. The data were analysed for age, sex and histological types using SPSS version 20 software. The results are presented in the form of simple frequency tables and percentages.
Results: A total of 190 patients were seen with histologically confirmed bladder cancer out of the 3933 patients with malignancies between the years 2006 and 2015, constituting 4.8% of all malignancies diagnosed in the same period and comprises 160(84.2%) males and 30(15.8%) females with male to female ratio of 5.3:1. Their mean age was 50.8, SD ±14.9 years and range from 1-90 years. The most common bladder cancer was squamous cell carcinoma with 97 (51.1%) cases. 81 (42.6%) patients had urothelial carcinoma, 5(2.6%) were metastatic carcinoma, 4(2.1%) were sarcomatoid carcinoma, 2(1.1%) were rhabdomyosarcoma and only 1(0.5%) case of a signet ring cell carcinoma was recorded.
Conclusion: Squamous cell carcinoma remained the most common histological type of bladder cancer in our setting followed by urothelial carcinoma. Preventive measures aim at eradicating urinary schistosomiasis, a predominant and known risk factor of bladder cancer in our environment will go a long way in curtailing the burden of this disease among our people.
Citation Format: Saddiku Malami Sahabi, Kabiru Abdullahi. Urinary bladder cancer in Sokoto, Northwestern Nigeria: A 10-year histopathological review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1212.
Abstract 1222: Functional single-nucleotide polymorphisms in the TGFb and TGFbRI gene and their association with prostate cancer in Western Mexicans
Authors: Martínez-Rizo Abril , González-Cordova Brenda , Peña-George Christopher , (CA-UAN-266) Cuerpo Académico de Investigación Bioquímica , Navarro-Partida José , González-Carrillo Martha , Arvizu-Gómez Jackeline , Álvarez-Rodríguez Adriana 
Published: August 2018

Abstract
Background: Prostatic carcinogenesis has been linked to chronic inflammation. Several studies demonstrated the duality of TGFβ during carcinogenesis. This pleiotropic cytokine participates in cell proliferation, migration and survival, epithelial-mesenchymal transition, and apoptosis, among other functions. An increase in its expression is associated with antiproliferative effects, tumor angiogenesis and metastasis of cancer cells. Single-nucleotide polymorphisms (SNPs) of the TGFB1 and TGFBR1 genes have been associated with risk and progression of many cancers.
Aim: To investigate the synergic role T29C (rs1800470) of the TGFβ gene and TGFBR1 rs334348 polymorphisms in risk, progression and severity of prostate cancer.
Materials and Methods: The present cases-control study includes 211 patients with PCa, and as controls 297 patients with benign prostatic hyperplasia (BPH) were obtained. The functional polymorphisms rs1800470 of the TGFβ gene and TGFBR1 rs334348 were detected by real-time PCR using the TaqMan probe system, according to the manufacturer's amplification recommendations. Hardy Weinberg Equilibrium was calculated by chi-square (χ2) test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were calculated. The haplotypes were analyzed using the Haploview program.
Results: The genotype frequencies of the SNPs analyzed in this work were no significant deviation from Hardy-Weinberg Equilibrium. Chi-square analysis established that there was no significant association between prostate cancer risk and TGFβ or TGFBR1 genotypes and alleles. Neither of the polymorphisms was associated with progression or severity of prostate cancer. Furthermore, the GT haplotype revealed protection for development of prostate cancer (OR=0.57, 95% CI (0.36-0.89) p=0.01).
Conclusion: To our knowledge, this research is the first genetic association study to show that GT haplotype confers protection in patients from Western Mexico with PCa.
Citation Format: Abril Martínez-Rizo, Brenda González-Cordova, Christopher Peña-George, Cuerpo Académico de Investigación Bioquímica (CA-UAN-266), José Navarro-Partida, Martha González-Carrillo, Jackeline Arvizu-Gómez, Adriana Álvarez-Rodríguez. Functional single-nucleotide polymorphisms in the TGFb and TGFbRI gene and their association with prostate cancer in Western Mexicans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1222.
Abstract 1232: Familial mesothelioma: Beyond BAP1
Authors: Cheung Mitchell , Ohar Jill A. , Howard Suzanne E. , Howard Timothy D. , Hesdorffer Mary , Testa Joseph R. 
Published: August 2018

Abstract
BAP1 germline mutations are associated with some, but not all, familial malignant mesotheliomas. We sought to identify new genetic risk factors from a large cohort of malignant mesotheliomas cases with a family history of cancers but no germline BAP1 mutation. Whole genome sequencing was performed on 15 samples (14 peripheral blood and 1 MM sample). Promising mutated candidate genes were identified in 12 of 14 BAP1 mutation-negative cases, with 3 different candidate genes mutated in 3 cases, 2 different candidates mutated in 5 cases, and 1 candidate mutated in 4 cases. Candidate genes encoded proteins involved in DNA damage repair, DNA polymerase, DNA and histone methytransferase, as well as mitotic control, helicase, and kinase factors. All mutations were confirmed by Sanger sequencing. Mutations included in/dels predicting frameshifts (4), splice site mutations (6), and missense mutations (14). Notably, in addition to being BAP1 mutation-negative, germline mutations were not identified in any of the genes known to be commonly mutated somatically in malignant mesothelioma, i.e., CDKN2A, NF2, TP53, SETD2, or PBRM1. Sequencing of blood and/or tumor DNA from several available affected members of these families validated co-segregation of mutations in candidate genes with the development of various cancers. Malignant mesothelioma specimens from two members of one family showed somatic loss of heterozygosity of the wild-type allele, indicating biallelic inactivation of the candidate gene—a suspected tumor suppressor locus—in these tumors.
Citation Format: Mitchell Cheung, Jill A. Ohar, Suzanne E. Howard, Timothy D. Howard, Mary Hesdorffer, Joseph R. Testa. Familial mesothelioma: Beyond BAP1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1232.
Abstract 1234: Somatic mutations of FAT1 in oral cancer are associated with tumor progression and survival
Authors: Liu Chung Ji , Lin Shu-Chun , Lin Li-Han 
Published: August 2018

Abstract
In recent years, the incidence and mortality rates of oral squamous cell carcinoma (OSCC) have increased worldwide. Therefore, understanding genomic alterations in OSCC carcinogenesis is crucial for appropriate diagnosis and therapy. Procadherin FAT1, which encodes 4588 amino acid residues, regulates complex mechanisms to promote oncogenesis or suppression of malignancies. Multiplex polymerase chain reaction (PCR)-based next-generation sequencing (NGS) revealed FAT1 somatic mutations. The clinicopathologic implications of FAT1 in OSCC were investigated using expression assays, and the functional role of FAT1 in HNSCC pathogenesis was determined using ectopic expression and knockdown experiments. Approximately 29% of patients with OSCC harbored damaging FAT1 mutations. Each type of mutation (missense, nonsense, and frameshift mutations) accounted for nearly one-third of deleterious mutations. FAT1 mutations correlated with lower FAT1 expression in tumors. The knockdown of the endogenous expression of FAT1 and exogenous expression of crucial FAT1 domains unequivocally indicated that FAT1 suppressed the migration and invasion capability of OSCC cells. Functional analysis suggested that nonsense mutations in FAT1 result in the loss of the suppression of tumor progression. FAT1 mutations and downregulation defined nodal involvement, lymphovascular permeation, and tumor recurrence. In addition, FAT1 mutations and downregulation are independent predictors of poor disease-free survival in patients with HNSCC. This study is the first to perform multiplex PCR-based NGS to indicate marked nonsynonymous FAT1 mutations in OSCC, which are prognostic indicators. The gene analysis strategy proposed for detecting FAT1 mutations may be a valid method for mutation screening.
Citation Format: Chung Ji Liu, Shu-Chun Lin, Li-Han Lin. Somatic mutations of FAT1 in oral cancer are associated with tumor progression and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1234.
Abstract 1247: Hereditary paraganglioma-pheochromocytoma syndrome: Patterns of presentation in a Brazilian oncogenetics clinic
Authors: Soares Diogo C. , Camacho Ana Milena G. , Achatz Maria Isabel , Formiga Maria Nirvana C. 
Published: August 2018

Abstract
Introductory Sentence: More than 35% of pheochromocytomas and paragangliomas (PPGL) are thought to occur due to an underlying genetic predisposition, which explain approximately 30% of familial cases. Methods: We analyzed data of four families with clinical and molecular diagnosis of PPGL followed at Oncogenetics Department of A.C. Camargo Cancer Center, from 2010 to 2017. Results: The proband of Family 1 is a 40-year-old woman with glomus jugulare paraganglioma and confirmed SDHB mutation. Her two children have the same mutation in SDHB gene and her son had the diagnosis of retroperitoneal paraganglioma at the age 13. The brother of the index case had a pheochromocytoma and her nephew had an abdominal paraganglioma at the age of 8. In the Family 2 the index case is a 33-year-old woman with paraganglioma of the carotid body bilateral and had a molecular diagnosis with SDHB mutation. There are no other paraganglioma cases in the members of this family. Family 3 initiated counseling in our clinics with a woman with paraganglioma of the carotid body bilateral at 25-year-old with recurrence at 35-year-old and it was found in genetic test a SDHD mutation. She had two cousins with bilateral cervical paraganglioma, but without genetic testing. Our fourth family: Man with pheochromocytoma at 28-year-old and mutation in the SDHD gene. A son with metastatic phaeochromocytoma in the retroperitoneum, mediastinum and lung at 11-year-old and bilateral carotid paraganglioma at 12-year-old. Sister of the index case with glomus jugulare paraganglioma at the age of 38. Conclusions: Although PPGL are rare tumors, it is estimated that up to 30-40% of cases are hereditary, based on this it is relevant to raise the PPGL syndrome suspicion and refer a paraganglioma or pheochromocytoma patient to a cancer genetic counseling. There are clear follow-up guidelines for the early detection of these tumors in carriers and the genotype-phenotype correlation can direct the diagnosis and in some cases the management of these patients.
Citation Format: Diogo C. Soares, Ana Milena G. Camacho, Maria Isabel Achatz, Maria Nirvana C. Formiga. Hereditary paraganglioma-pheochromocytoma syndrome: Patterns of presentation in a Brazilian oncogenetics clinic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1247.
Abstract 1254: Metformin's potential as a breast cancer preventative agent by altering epigenetic patterns
Authors: Tyndall Caitriona , Lam Charlene , Gunter Marc , Flanagan James 
Published: August 2018

Abstract
Metformin is one of the most commonly prescribed Type II Diabetes Mellitus (T2DM) drugs and has been shown in diabetic long-term users to reduce the likelihood of breast cancer by 56%. Breast cancer is the most commonly diagnosed cancer in the UK accounting for 55,000 new cases per year. It has been estimated that as much as 27% of cases could be prevented based on current knowledge. This study aims to investigate the novel hypothesis that metformin acts as a preventative agent by altering epigenetic patterns in non-cancerous breast epithelial cells and the T2DM environment, namely hyperinsulinemia and hyperglycaemia, potentially modulates this.
Crystal Violet cell viability assay and Western Blot for p-AMPK, a known target for metformin, were performed to assess the response of two non-cancerous breast epithelial cells lines, MCF10A and MCF12A, to metformin in a range of insulin and glucose concentrations. Western blot was performed to assess changes in histone post-translational modifications (PTMs), such as H2K27ac and H3K27me3, following 3-days treatment with metformin at 2.5mM and 5mM. Additionally, we conducted an Illumina MethylationEPIC Array on MCF10A and MCF12A cell lines treated for 3-days with 2.5mM and 5mM metformin. Pyrosequencing assay was used to further validate interesting CpG sites.
Our findings suggest non-cancerous breast epithelial cells, MCF10A and MCF12A cell lines, are sensitive to metformin following 3 and 7-days treatment. Further to this, our data suggests the T2DM environment impacts the effectiveness of metformin where low glucose and high insulin significantly increase metformin effectiveness in MCF10A and MCF12 cell lines following 3-day treatment, respectively. Metformin treatment leads to the activation of p-AMPK in normal breast epithelial cells. Analysis of Illumina MethylationEPIC array suggests metformin in hyperglycaemic and hyperinsulinemic conditions induces differential DNA methylation changes in MCF10A and MCF12A non-cancerous breast epithelial cell lines and the effects are dose dependent. Of the 850,000 probes, 13 CpG sites in MCF10A and 5 CpG sites in MCF12A showed significant changes in methylation following metformin treatment (p&lt;0.001).
In summary, this study has shown a potential mechanism of metformin action through altering of epigenetic patterns in non-cancerous breast epithelial cells. Future work aims to further explore epigenetic changes induced by metformin in the context of the T2DM environment and whether these changes could potentially predict reduced breast cancer risk.
Citation Format: Caitriona Tyndall, Charlene Lam, Marc Gunter, James Flanagan. Metformin's potential as a breast cancer preventative agent by altering epigenetic patterns [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1254.
Abstract 1259: Loss of TFF1 promotes growth and chemotherapeutic resistance in gastric cancer
Authors: Chen Zheng , Li Zheng , Soutto Mohammed , Wang Weizhi , Zhu Shoumin , Corvalan Alejandro , Xu Zekuan , El-Rifai Wael 
Published: August 2018

Abstract
Background: Downregulation or loss of TFF1 expression occurs in more than half of human gastric adenocarcinomas through gene deletions, mutation, and a loss of heterozygosity or hypermethylation. Our previous studies have shown that Tff1 knockout (KO) in mice induces gastric lesions from low- grade dysplasia (LGD), high- grade dysplasia (HGD) to adenocarcinoma. BRD2, a family member of BET proteins, promotes aberrant gene expression in a variety of malignant tumors. In this study, with the analysis of Tff1 KO mice and human gastric cancer tissue samples, we discovered that loss of Tff1 promotes gastric cancer proliferation and drug resistance through upregulating BRD2 expression level.
Methods and Results: Integration Next Generation Sequencing data analysis in both Tff1 KO mice and human gastric cancer tissue samples demonstrated that miR-143-3p was significantly down-regulated in both mice and human gastric cancer samples (P&lt;0.05). Our findings were further validated by RT-PCR in Tff1 KO mouse gastric legions (LGD and adenocarcinoma) and 3 different cohorts of human gastric cancer tissue samples from USA, Chile, and China. Using different gastric cancer cell models we further confirmed the decrease of miR-143-3p regulated by loss of TFF1. Next, we wanted to find out the downstream effector of miR-143-3p down-regulation. Western blot data showed that BRD2 protein level was regulated by miR-143-3p in 4 gastric cancer cell lines. BRD2 3'UTR luciferase reporter assay further confirmed that miR-143-3p decreased BRD2 protein expression through directly binding to its 3'UTR sites. These data suggested that, for the first time, BRD2 is a direct downstream target of miR-143-3p. At the meantime, the reconstitution of TFF1 in gastric cancer cells up-regulated miR-143-3p expression level, which in turn, decreased the protein expression levels of BRD2, MYC and BCL-2. Using western blot, we showed the synergistic effect of BRD2 inhibitor and CDDP chemotherapy in human gastric cancer cells. Data from 320 human gastric cancer patients demonstrated that high BRD2 expression level in gastric cancer tissues significantly decreased the overall patient survival rate (P&lt;0.0001).
Conclusion: This study unveils, for the first time, loss of TFF1 promotes BRD2 activation in gastric cancer through decreasing miR-143-3p. This axis presents novel therapeutic opportunities by using approaches that reconstitute miR-143-3p or utilizing the recently developed clinical trials in human gastric cancer.
Citation Format: Zheng Chen, Zheng Li, Mohammed Soutto, Weizhi Wang, Shoumin Zhu, Alejandro Corvalan, Zekuan Xu, Wael El-Rifai. Loss of TFF1 promotes growth and chemotherapeutic resistance in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1259.