bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of kinase domain duplications across diverse cancer types in Chinese population by comprehensive genomic profiling (CGP).
Authors: Wang Baohua , Yu Ruoying , Ou Qiuxiang , Bao Hua , Wu Xue , Shao Yang , Zhang Tao 
Published: May 2020

e13522 Background: Kinase domain duplication (KDD) has recently been recognized as oncogenic and targetable mutations in some cancers. EGFR KDD was identified as an oncogenic driver in lung cancer showing partial response to EGFR TKI. BRAF KDD was reported in diverse tumor types with clinical response to RAF-targeted therapy. We retrospectively investigated the prevalence of KDDs in multiple cancer types of a large Chinese population. Methods: 50742 unique cancer cases were analyzed by comprehensive genomic profiling (CGP). DNA was extracted from formalin-fixed paraffin-embedded specimens (FFPEs), fresh tissue, blood or plasma samples and sequenced with gene panels targeting 400+ cancer-relevant genes. Among them, 53 cases were detected with KDD of various kinases. Results: In this Chinese cohort, KDD was identified in 0.1% of the total population across multiple cancer types including lung cancer (39), breast cancer (5), gastric cancer (3), colorectal cancer (2), mucoepidermoid carcinoma (1), unknown (3). The median age at diagnosis was 54 which was younger than the 60 yrs median age of total population. The distribution of KDDs was in EGFR(34) MET(5), JAK1(2), BRAF(2), FGFR2(2), FGFR1(1), JAK2(1), LYN(1), MAP3K1(1), RAF1(1), RET(1), AKT3(1), and CDK8(1). Thirty-one lung cancer cases were detected with EGFR-KDD, including kinase duplications of exon18-25 (22), exon17-25 (6), exon18-26 (2), exon14-26(1). Three patients with EGFR-KDD exon18-25 showed partial anti-tumor response to target therapy. MET-KDD was exclusively found in lung cancer involving the duplication of MET exon15-21 (2), exon14-17 (1), exon15-16 (1) and exon12-21 (1) while FGFR1/2-KDD was observed only in gastric cancer. Two female patients with breast cancer were detected with JAK1-KDD at age of 45 and 37, respectively. The canonical BRAF-KDD of exon 10-18 was identified in one female patient diagnosed of lung adenocarcinoma at age of 49. Frequently altered genes in patients with KDD were TP53(72%), EGFR (23%), FAT1(13%), BRCA1(10%). MCL1 amplification, a known oncogenic alteration, was identified in fifteen patients (11 EGFR-KDD,2 MET-KDD, 1 BRAF-KDD, 1 JAK2-KDD), representing the most common copy number variation observed. Conclusions: Kinase KDDs were rare but potentially oncogenic mutations in diverse cancer types with clinical outcome of EGFR-KDD to target therapy in lung cancer. Cancer-type specific KDDs were identified including MET-KDD in lung cancer, FGFR1/2-KDD in gastric cancer and JAK1-KDD in breast cancer.
Clinicopathological features of patients with ovarian and breast cancer with BRCA mutation.
Authors: Ozkan Metin , Fırat Sedat Tarık , Coşar Ramazan , Bozkurt Oktay , Inanc Mevlude , Dogan Muhammet Ensar 
Published: May 2020

e13524 Background: Breast cancer is the most common cancer and the leading cause of cancer death in women. Ovarian cancer contributes significantly to mortality and morbidity rates. BRCA1 and BRCA2 are the best known genes associated with breast and ovarian cancer, which are important in DNA repair and transcriptional regulation. Methods: In this study, we retrospectively analyzed the clinicopathological features of breast and ovarian cancer patients who were found to have BRCA 1/2 mutations in Erciyes University Medical Oncology between 2009-2019. Results: BRCA mutation was detected in 14 patients with breast cancer and 10 patients with ovarian cancer. The median age of patients with breast cancer was 41 (25-67). Of 14 BRCA mutated patients, 9 (64 %) patients had BRCA2 mutations while 5 (36 %) patients had BRCA1 mutations. All patients had invasive ductal carcinoma. Of 14 patients, 7 patients were grade 3, 6 patients were grade 2, 1 patient was grade 1. At the time of diagnosis, 5 of 14 patients were stage 3 and 5 patients were stage 4. 4 (80%) of 5 patients with stage 4 had BRCA 2 mutation. 5 of 10 patients who received adjuvant therapy after surgery had 4 or more lymph node metastases. Hormone receptor positive / HER2 negative disease was the most common molecular subgroup (8/14, 57%). Five patients were triple negative histology. 4 (80%) of triple negative patients had BRCA1 mutation. Ovarian cancer developed in 2 of 14 patients who had breast cancer with BRCA mutation. Median age of patients with ovarian cancer with BRCA mutation was 52.5 (19-67). 2 of 10 patients with ovarian cancer had germ cell tumors and 8 had epithelial serous carcinoma. Of 10 BRCA mutated patients, 7 (70 %) patients had BRCA2 mutations while 3 (30 %) patients had BRCA1 mutations. Both patients with germ cell tumors were stage 1 at the time of diagnosis, 7 of the patients with epithelial serous carcinoma were stage 3, and 1 was stage 2. While patients with germ cell tumors were followed without recurrence, 6 patients with epithelial serous carcinoma developed recurrence, and all of these patients were platinum sensitive. Breast cancer developed in 1 patient with BRCA1 mutation at follow-up. All patients were alive according to the last control date. Median DFS was 29 months. Conclusions: BRCA-related breast cancer is characterized by a more aggressive phenotype than sporadic breast cancer, BRCA1-associated breast cancer is more frequently high-grade and triple negative histology. BRCA-related ovarian cancer is more sensitive to treatment, especially platinum-based chemotherapy, and is associated with improved prognosis.
YsRNA aberrant expression in colorectal cancer patients.
Authors: Novikova Inna A. , Kutilin Denis S. , Timoshkina Natalya N. , Poluektov Sergey I. , Tolmakh Roman E. , Dashkov Andrey V. , Haragezov Dmitry , Kolesnikov Evgeniy N. , Dontsov Vladimir A. , Soldatkina Natalya V. , Petrov Dmitry S. , Gevorkyan Yuriy A. , Kit Oleg Ivanovich 
Published: May 2020

e13525 Background: Cancer is a disease characterized by uncontrolled cell proliferation. DNA replication is the main driving force behind cell proliferation in both normal development and cancer. Non-coding Y-RNAs are important factors in initiating DNA replication in the nuclei of human cells. Excessive expression of Y-RNA is characteristic of tumors of the bladder, cervix, kidney, lung and prostate. It has also been shown that the level of small RNAs formed from the 3'- and 5'-ends of Y-RNA is significantly higher in patients with certain types of cancer compared to healthy people, therefore, these RNAs may have diagnostic value. However, for colon tumors, data on the expression of Y-RNA/YsRNA obtained in previous studies are ambiguous. The aim of the study was to analyze the differential expression of YsRNA in the tumor and non-tumor tissue of patients with CRC using next generation sequencing (NGS). Methods: For NGS, 10 patients with CRC (colon adenocarcinoma, G2). were selected. Small RNA fractions were isolated using the mirVana miRNA Isolation Kit protocol (Ambion, Life Science Technologies, USA). The library was prepared for sequencing using the TruSeq Small RNASample Preparation Kit (Illumina, USA). Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The determination of the copy number of Y-RNA fragments (YsRNA, 19-34 bp) was carried out by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences presented in the databases. In the analysis of differential expression, the edgeR method, implemented in the R language, was used. Results: Several different fractions of YsRNA were detected in tumor and non-tumor tissues: hY3sRNA (the most represented fraction, more than 70%), hY5sRNA and hY1sRNA. In tumor tissue relatively non-tumor, a statistically significant (p < 0.001) increase of 4 and 6 times the number of copies of hY3sRNA and hY5sRNA, respectively, was detected. The function of YsRNA in tumor and normal cells has not yet been established. Conclusions: Thus, in the tumor colon tissue differential expression of 2 YsRNA fractions - hY3sRNA and hY5sRNA, was detected. These YsRNAs can become promising tumor markers and targets for the treatment of CRC, as well as make certain contributions to understanding the mechanisms of carcinogenesis in this nosology.
Comprehensive analysis of advanced-stage solid tumors from TCGA reveal widespread variation of genomics evidence levels across cancer types.
Authors: Weeraratne Dilhan , Ferreira Elisa Napolitano , Mitne Neto Miguel , Huang Hu , Brotman David , Fraga Ana Maria , Ramalho Rodrigo Fernandes , Burger Matheus , Felipe-Silva Aloisio Souza , Snowdon Jane 
Published: May 2020

e13547 Background: Improved scalability and affordability of next generation sequencing (NGS) has pivoted cancer care toward genomics-driven treatment decisions. Particularly in advanced-stage or refractory cancer, clinical insights gleaned from NGS have become an integral option as these patients have typically exhausted all lines of available therapy. As precision oncology evolves, NGS is expected to have a differential impact based on the cancer type. In this study, a comprehensive NGS panel was used to determine the strength of clinical evidence in various advanced stage tumor samples from The Cancer Genome Atlas (TCGA). Methods: A hybrid capture panel, Oncofoco, was developed to evaluate SNVs, INDELs, CNVs and TMB in 366 genes. The panel’s utility was validated by interrogating a broader cohort of 2847 TCGA samples (advanced tumors with T3 or T4; or N > = 1; or M > = 1). Watsonä for Genomics, an artificial intelligence offering, was used for variant interpretation and annotation of the 366 genes. A clinical evidence classification system that evaluated the strength of biomarker/drug response associations was used for annotation with level 1/R1 strongest and level 4 weakest from clinical literature, FDA drug labels and guidelines (PMID:28890946). Results: The highest level of evidence for the top nine frequently occurring advanced stage cancers in TCGA is shown in Table. Conclusions: Thyroid cancer and cutaneous melanoma have emerged as the cancer types with the most level 1 evidence (FDA approved drugs) owing to BRAF V600E mutations. Kidney and prostate cancers show no cases with level 1 evidence and also had the largest fraction of unactionable tumors. Over half of colorectal cancer cases had level R1 resistance evidence attributed to KRAS and NRAS mutations. The clinical utility of NGS in late-stage refractory cancer varies widely by tumor type. The presence of level 3 and level 4 evidence in all cancer types bodes well for the development of new targeted drugs. [Table: see text]
Missed opportunities? A retrospective analysis of lung cancer screening utilization among patients with lung cancer.
Authors: Olazagasti Coral , Kohn Nina , Aviles Karen , Ehrlich Matthew , Hoilett Aldane , Seetharamu Nagashree 
Published: May 2020

e13565 Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tobacco smoking is implicated as the causative factor in 85% of LC. The U.S. Preventive Services Task Force (USPSTF) and National Comprehensive Cancer Network (NCCN) recommendations for annual low-dose CT chest (LDCT) for LC screening in high risk adults who meet appropriate criteria, which primarily focuses on age and smoking history. Medicare coverage for LC screening for eligible individuals went into effect in February 2015. Despite this, screening rates remain low and patients with LC are typically diagnosed at a later stage. We conducted a single center retrospective analysis of patients with established diagnosis of lung cancer to evaluate if screening guidelines were appropriately followed prior to the cancer diagnosis. Methods: Patients diagnosed with LC between 2016 and 2019 were included in the analysis. Charts were reviewed for demographics, detailed smoking history, as well as histology and stage of LC. Associations between categorical factors and screening and were examined using the chi-square test. Associations between continuous and ordinal factors and screening and were examined using the Mann-Whitney test. Results: A total of 530 charts were reviewed. Of those, 52.5% (278) met NCCN and/or USPSTF criteria and 10.8% (30/278) underwent screening. The median age for those who were screened was 69 years. There was no association between age at diagnosis and screening. There was a significant association between active smoking status and screening (p < 0.0191). An average of 16.8% (16/95) of current smokers and 7.7% (14/183) of former smokers were screened. Patients who had screening CT scans were diagnosed at earlier stages of LC compared to those who were not screened (p < 0.0083) [table]. Conclusions: Our study showed that despite established guidelines for LC screening and insurance coverage, a vast majority of screening-eligible LC patients have never had LDCT. We found that patients who underwent screening as per guidelines were diagnosed at earlier stages of disease compared to those not screened, which goes along with published data. Ongoing efforts to increase awareness and adherence to LC screening guidelines will be of paramount importance in improving early detection and reducing mortality from LC. [Table: see text]
Detect Early Be Safe–Care for Mother (DEBS-CaM) project: School-based interventions to improve awareness and screening for breast cancer among the young mothers of Kerala.
Authors: Warrier Narayanankutty , Sankar Uma V , P S Sreedharan , V Nirmal , K V Sajeevan , Sherif Ajmal 
Published: May 2020

e13570 Background: The prognosis rate among the breast cancer patients was less than 50% in India when compared to European countries due to the late diagnosis and most of them diagnosed at an advanced stage of disease. Early detection can reduce the risk of advancement of disease by 30%. There is an immediate need to target both younger population to empower the women with the knowledge on their breast cancer risk and self-breast examination (SBE). So the project aimed to examine the efficacy of a Brief Motivational Intervention (BMI) and Student based Parental intervention (SBPI) based on motivational interviewing as a universal preventive and early diagnosis interventions to fight against breast cancer among the school students using a randomized factorial design. Methods: Daughters and Mothers are always a good dyads for doing an personal health intervention. Since it is a ‘matter of closeness’, a mother and a daughter can easily communicate, intervene and ensure the act of doing in self breast examination.We identified 85 schools (including the Junior high and senior high schools in the northern region of Kerala. The female resource person from the MVR Cancer Centre & Research Institute delivered the awareness session on risk factors of breast cancer breast and SBE. So the attendees demonstrated the SBEs to their mothers and ensure the act of doing monthly. The study utilized a 2 × 2 × 3 factorial design, crossing a BMI; (yes, no) and SBPI (yes, no), with one within-subjects factor (Time; baseline and 10 months). Over 10 months, we recruited cohorts of parent-student dyads and randomize by dyad to one of four experimental conditions: BMI only and BMI and SBPI only. We did the randomization by computer algorithm to ensure that the experimental conditions will balance on prognostic indicators of students and their mother’s on breast cancer risk and including waist to hip ratio, frequency of SBE, healthy dietary intake and physically active. Results: Baseline data collected from students and parents during the summer prior to college matriculation. Follow-ups occurred at 10 months post-baseline for parents in the face to face interview with students at their schools. We found 17% of mothers detected any kind of breast abnormalities and among that, 68% of mothers went for further detailed diagnostic tests. Conclusions: It is an innovative approach incorporating the principles of primary prevention and early detection for the breast cancer among the young mothers of Kerala.
Proximity to oil refineries and risk of cancer: A population-based analysis.
Authors: Williams Stephen B. , Shan Yong , Jazzar Usama , Kerr Preston , Okereke Ikenna , Klimberg V. Suzanne , Tyler Douglas S. , Putluri Nagireddy , Lopez David S , Prochaska John D , Elferink Cornelis , Baillargeon Jacques G. , Kuo Yong-Fang , Mehta Hemalkumar B 
Published: May 2020

e13586 Background: Proximity to oil refineries and cancer incidence is largely unknown. We sought to compare the incidence of cancer (bladder, breast, colon, lung, lymphoma, and prostate) according to proximity to an oil refinery in the State of Texas. Methods: A total of 6,302,265 persons aged ≥20 years from January 1, 2001 through December 31, 2014 were identified. We used zero-inflated Poisson regression models to examine the association of proximity to an oil refinery with cancer incidence. Results: We observed that proximity to an oil refinery was associated with a significantly increased risk of incident cancer diagnosis across all cancer types. For example, persons residing within 0-10 (Risk Ratio (RR) 1.16, 95% Confidence Interval (CI) 1.13-1.19) and 11-20 (RR 1.08, 95% CI 1.05-1.11) miles were significantly more likely to be diagnosed with lymphoma than individuals who lived within 21-30 miles from an oil refinery. We also observed differences in stage of cancer at diagnosis according to proximity to an oil refinery. We also found persons residing within 0-10 miles were more likely to be diagnosed with distant metastasis and/or systemic disease than people residing 21-30 miles from an oil refinery. The greatest risk of distant disease was observed in patients diagnosed with bladder cancer living within 0-10 vs. 21-30 miles (RR 1.33, 95% CI 1.06-1.68), respectively. Conclusions: Proximity to an oil refinery was associated with an increased risk of multiple cancer types. We also observed significantly increased risk of regional and distant/metastatic disease according to proximity to an oil refinery.
Impact of the molecular pathology of breast cancer on mortality rates and overall survival in a Haitian cancer clinic.
Authors: Bernard Joseph , Henderson Rebecca , Alexis Lynn Gabrielle , Gilbert Doukens Patrick , Pierre Lenz Sacha Christyl , DeGennaro Vincent A. 
Published: May 2020

e13588 Background: Breast cancer in the most common malignancy among women in Haiti and is mostly diagnosed at an advanced stage. While it is well known that molecular subtype is a prognostic factor, it needs to be investigated among Haitian patients with breast cancer. This study aimed to evaluate the impact of molecular classification of breast cancer on the survival of patients managed in Haiti’s largest cancer clinic. Methods: A retrospective study was conducted on the breast cancer patients of Innovating Health International (IHI) in Port-au-Prince, Haiti from January 2014 to December 2018. Chart review included all patients with breast cancer and tested for molecular classification. Data on variables such as date of admission, age, TNM staging, molecular classification, outcome and date of death were collected for the analysis. Mortality rate and median overall survival (OS) were estimated as of December 31st, 2019 and stratified according to molecular subtypes. Results: Among the 948 breast cancer cases diagnosed for the study period, 234 (24.7%) of them had a complete molecular classification. The mean age was 51.5 years [range: 23-94]. 55.1% of the patients were ER-positive, among them 33.7% ER+/PR+/HER2-, 15.4% ER+/PR-/HER2-, 2.1% ER+/PR-/HER2+ and 3.8% ER+/PR+/HER+ (triple positive). There were overall 25.6% of luminal A and 29.5% of luminal B cases. 44.9% were ER-negative, among them 14.1% ER-/PR-/HER2+ (HER2-enriched) and 29.1% ER-/PR-/HER2- (triple-negative). 92.2% of the patients had advanced breast cancer (stages IIB to IV). 29.5% had metastatic breast cancer, 22.8% for luminal A cases, 27.0% for luminal B, 36.7% for HER2-enriched and 32.8% for TNBC. Overall mortality rate was 42.3%, respectively 33.3% for luminal A cases, 37.7% for luminal B, 42.4% for HER2-enriched cases and 55.9% for TNBC. Median OS was not yet reached for luminal A, luminal B and HER2-enriched breast cancer, with a respective mean survival of 52.4 months, 51.3 months and 51.6 months. However, OS was 30.6 months for triple-positive breast cancer and 23.7 months for TNBC. Conclusions: Patients with luminal A breast cancer were less likely to have metastatic disease and thus had lower mortality rate and better overall survival. This was likely due to its less aggressive biology and the availability of hormone therapy. Poor availability and inaccessibility of HER2-targeted drugs were the main cause of the higher mortality rate among HER2-enriched patients. TNBC remains the most aggressive subtype.
Can body size explain the excess cancer risk in men?
Authors: Radkiewicz Cecilia , Sjölander Arvid , Benyi Emelie , Lambe Mats , Dickman Paul , Sävendahl Lars , Edgren Gustaf 
Published: May 2020

e13593 Background: Men are at increased risk of a majority of malignancies affecting both sexes. Since tall stature is associated with elevated cancer risk and since men are taller than women, we decided to investigate to what extent body stature, as a proxy for stem cell number within tissue, can explain the excess cancer risk in men. Methods: We performed a population-based cohort study investigating the association between male sex and cancer, accounting for body height. The analyses included all Swedish men and women with an adult height registration in either the Swedish Passport Register, the Conscription Register, and/or the Medical Birth Register (n = 6,156,659). Height data was linked to the Swedish Cancer Register where we observed 285,778 non-sex-specific cancer cases, diagnosed in 1960-2012. We applied contemporary causal mediation analysis methodology to assess the relative effect of male sex on lifetime cancer risk mediated by body height. Results: A vast majority of the investigated cancer sites were significantly associated with male sex (33 of 39) and height (27 of 39). The proportion of the excess cancer risk in men explained by sex differences in body height ranged from 0.5% (laryngeal) to 100% (salivary glands, colon, melanoma, and AML). The effect of body height and the mediated effect through height on cancer risk was most consistent and pronounced in malignancies with weak, few, or no known risk factors. Conclusions: A large proportion of the excess cancer risk in men is explainable by height. There is no known, height-associated cancer risk factor strong enough to provide an alternative pathway. Our findings supports the notion that a substantial proportion of cancer cases arise stochastically rather than are caused by underlying hereditary and/or environmental factors.