bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative gene expression analysis in gliomas with different IDH1/2 status.
Authors: Timoshkina Natalya N. , Kit Oleg I. , Pushkin Anton , Antonets Anna V. , Rostorguev Eduard Evgenevich , Porksheyan David H. , Kavitskiy Sergey E. , Kuznetsova Natalya S. 
Published: May 2019

e13008 Background: The new 2016 WHO classification of tumors of the central nervous system takes into consideration mutational status of IDH genes. Research of molecular changes in gliomas remain to be an actual issue. We analyzed the gene expression of some significant pathways in gliomas. Methods: 27 patients (12 females, 15 males) aged from 27 to 76 years with verified brain tumors (glioblastomas (G4) – 67%, anaplastic astrocytomas and oligoastrocytomas (G3) – 11%, astrocytomas (G2) – 22%) were investigated. 7 mutations in the IDH1 gene and 5 ones in IDH2 in fresh frozen tumor tissues were detected by RT-qPCR with Therascreen IDH1/2 RGQPCR kit (Qiagen). The expressions of EGFR, SMAD4, SMAD7, SMO, NOTCH1, NOTCH2, HBP1, HIF1A, EGLN1, EGLIN3, KDM1B, KDM1A, MSI1, MSI2, TET1 genes in tumor and normal brain tissue obtained while surgical access were assessed with RT-qPCR. PSMC, TBP and RPLO were used as reference genes. Results: Analysis of IDH1/2 status revealed only R132H mutation of IDH1 in 6 patients. The ratio of the relative expression of genes in tumor tissue with mutation and wild-type and the significance of the differences in the Mann-Whitney test are presented in the table below . Conclusions: Expression of SMAD7, EGLN1, EGLN3 as an activating factor of TGF-b-signaling pathway potentially may be used as an additional prognostic marker of gliomas progression.[Table: see text]
A multi-institutional investigation assessing prevalence of germline genetic alterations in Chinese patients with gastric carcinoma.
Authors: Zhang Yinjie , Wang Xicheng , Zhu Changbin , Zhang Xiaotian , Wei Qing , Ren Lvzhi , Shao Di , Gao Jing , Li Yan Yan , Zhang Jingdong , Chen Xiao-Bing , Wang Chaojie , Meng Qiu , Wang Xin , Liu Baorui , Shen Lin 
Published: May 2019

e13020 Background: Gastric carcinoma is one of the most common malignancies in east asian. Previous studies demonstrated around 10% of patients with gastric cancer were found to have pathogenic germline variants. While, predisposition genes of gastric cancer in Chinese patients are still largely unknown. Thus, we aim to delineate prevalence of deleterious germline mutations in Chinese gastric patients with hereditary high-risk familial cancer history. We also aim to analyze clinical relevance of deleterious germline mutations. Methods: Forty index cases were recruited from 7 institutions in China. DNA samples extracted from blood specimens were captured using a 171-cancer predisposition gene panel and then sequenced by MGI-SEQ 2000 platform. Germline variants were determined to be deleterious according to the ACMG 2015 guidelines. Pathogenic and Likely pathogenic germline variants were further validated by Sanger sequencing. Results: 12 of 40 (30%) probands had 13 pathogenic/likely pathogenic germline variants involving 11 different genes: CHEK2 (n = 2), SPINK1 (n = 2), BLM (n = 1), CDH1(n = 1), EXT2 (n = 1), MLH1 (n = 1), MSH2(n = 1), MUTYH (n = 1), PALB2 (n = 1), NF1 (n = 1), ERCC2 (n = 1). For patients with multiple primary cancers, pathogenic germline alterations were exclusively presented (5 out of 12) (P=0.003). Besides,27 germline variants (like EPCAM, RAD54B, FANCD2, FANCA) with uncertain significance in 15 patients were predicated to be deleterious via in silico predictors. Conclusions: This multi-institutional study identified 30% (12/40) of Chinese gastric cancer patients with family history to have deleterious germline alterations. And potential deleterious variants were also identified. Our data illustrates a significantly distinguished spectrum of germline variants compared with Caucasian ones. This may indicate unique carcinogenesis of gastric cancer in Chinese patients. Since patients with pathogenic or likely pathogenic germline variants have dismal clinical outcome and higher rate of multi-cancer occurrence, genetic counseling of gastric cancer should be considered for individuals with family history at their early age.
MUC16 germline mutations may predispose inherited cancer family members to lung adenocarcinomas.
Authors: Wang Tao , Liu Hong , Xiao Shanshan , Mao Ruifang , Lin Rui 
Published: May 2019

e13039 Background: Familial lung cancer is rare. Previous studies have identified random EGFR mutations associated with the inherited lung cancer. Reports also show that TP53 and CDKN2A mutations may predispose individuals to lung cancer, and MUC16 plays important roles in tumorigenesis and metastasis of lung cancer cells through regulating TP53. However, the molecular findings of familial lung cancer are still few. Methods: We have identified an extremely rare family, four siblings diagnosed with lung adenocarcinomas and one with bladder cancer; all lung cancer patients had multiple synchronous nodules. Their father was also lung cancer patient and deceased. We extracted tumor tissue DNA, genomic DNA (gDNA) and circulating cell-free DNA (ctDNA) from the 5 patients and analyzed the DNA samples using a 500-gene next generation sequencing (NGS) panel. Results: TP53 P72R and other 3 CDKN2B-AS1 germline mutations were identified in all the 5 patients. Although the 3 CDKN2B-AS1 mutations are commonly occurred in population according to dbSNP, these observations are consistent with a hypothesis that TP53 P72R and the CDKN2B-AS1 germline mutants may synergize in predisposing the family members to cancer. Interestingly, 3 MUC16 mutations ((rs754254000, rs754856910, and rs746152510) were all identified in the four lung cancer patients, but none were identified in the bladder cancer patient. All of the 3 MUC16 mutants had very low population allele frequency (all below 0.1%,) suggesting that the MUC16 germline mutations may play roles in the familial lung cancer, which is consistent with previous reports demonstrating the involvement of MUC16 in lung cancer cell growth. Moreover, all the four lung cancer patients had somatic mutations of EGFR L858R/exon 19 deletion prior to treatment with EGFR tyrosine kinase inhibitor (TKI), including one patient with L858R and exon 19 deletion in different tumor nodules, which is consistent with molecular characteristics in synchronous primary lung cancer. Conclusions: We have demonstrated in this study that germline MUC16 mutations may predispose the inherited cancer family members to lung adenocarcinomas. This study provides a clue of the cause of familial lung cancer and also warrants further mechanistic study of MUC16 gene in lung cancer.
Procancerous immune cells in primary tumor is associated with breast cancer recurrence.
Authors: Takeshita Takashi , Yan Li , Takabe Kazuaki 
Published: May 2019

e13042 Background: Breast cancer (BC) recurrence is largely determined by cancer factors as well as host factors. It has been implicated that infiltrating immune cells play critical roles in long term survival. We hypothesize that immune cell infiltration profile rather than clinical characteristics or gene expression signatures of the primary tumors associate with the timing of cancer recurrence. Methods: 308 primary BCs in TCGA with cancer recurrence data was divided into; recurrence < 2 years (Early, n = 103), 2-5 years (Late, n = 20), and no recurrence > 5 years (Control, n = 185). 1410 primary BCs in METABRIC with BC specific death data was divided into; death < 10 years (Early Death, n = 499), death > 10 years (Late Death, n = 123), and survived > 10 years (Survivors, n = 788). Results: We found that Early tumors demonstrated more aggressive clinical characteristics such as larger tumor, more lymph node metastases, higher pathological grades, higher Stages, and negative estrogen and progesterone receptors, compared with Control tumors. On the other hand, no clinical characteristics of Late tumors were significantly different from Control tumors, which implicate that clinical characteristics cannot distinguish late recurrence from Control. Gene set enrichment analyses revealed that there was no significant gene sets that enriched with Early nor Late recurrence compared with Control, which implicate that gene expression signatures cannot distinguish recurrent tumor from Control. Utilizing CIBERSORT algorithm, we found that M1 was low and M2 was high macrophages in Early compared from Control. Further, anti-cancer lymphocytes, memory CD4 T cells and gamma delta T cells, were significantly lower, and pro-cancerous regulatory T cells were significantly higher in Early and Late compared from Control. In agreement, cytolytic activity score that assess immune cell killing were significantly lower in Early and Late compared from Control. Interestingly, only elevation of regulatory T cells was similar in METABRIC cohort when Early Death and Late Death were compared with Survivors. Conclusions: We found that not clinical characteristics or gene expression signatures, but pro-cancerous immune cells in primary BC associate with cancer recurrence and breast specific death.
Results of NGS panel of hereditary breast and ovarian cancer in Lebanese women.
Authors: Al Ajami Joseph , Jalkh Nadine , Moubarak Ghadi , Eid Roland , Haddad Fady , Kattan Joseph Gergi , Ghosn Marwan , Atallah David M. , Chouery Khoury Eliane , Kourie Hampig Raphael 
Published: May 2019

e13045 Background: Hereditary breast (BC) and ovarian cancer (OC) genetic alterations are considered the most prevalent among familial cancer. To date, four studies have exposed the mutations related to hereditary BC predisposition in the Lebanese population , with percentage of BRCA-related pathogenic mutations ranging between 5 % and 15 %. Methods: Between 2017 and 2019, 117 patients with high risk hereditary breast and ovarian cancer were referred to undergo the testing at the Unité de Génétique médicale (UGM) of Saint-Joseph University of Beirut, Lebanon. The sequencing was accomplished by using the 21-panel Next-Generation Sequencing (NGS) method for all of our patients, to which we also added the MLPA technique followed by the Sanger sequencing for validation whenever a genetic alteration was found. Results: From 117 Lebanese women with high-risk hereditary breast and ovarian cancer predisposition, 19 pathogenic mutations were identified in this study: 11 BRCA1, 1 BRCA2, 2 PALB2, 1 ATM, 1 CDH1, 1 MSH6, 1 RAD51C, and 1 BRIP1. Among those, 13 patients had BC, one had OC and five were healthy individuals. Five similar mutations were found within the BRCA1 gene, the p.C44F mutation, accounting for 45.4 %, thus suggesting a founder effect. Average age at diagnosis in the BC patients carrying a mutation was 41 years and 38.5% had a triple negative BC. Conclusions: The overall pathogenic mutation rate was equal to 16.2% while the BRCA deleterious mutation rate was 10.3% lower to those reported in the literature. The p.C44F mutation appeared five times suggesting a founder effect. [Table: see text]
Colorectal cancer: Improving screening in a rural clinic.
Authors: Le Thuy Thanh Thi , Johnson-wall Helen 
Published: May 2019

e13054 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Between 2012-2016, the age adjusted mortality rate was 18-25 per 100,000 persons in Robeson County, North Carolina. During this timeframe, it is estimated that if all people aged 50 and older in NC were routinely screened, 40 out of 100 deaths from late stage CRC can be prevented. A chart review in a rural primary care clinic identified patients not being appropriately screened for targeted intervention. Methods: Our retrospective chart review at Lumberton Medical Clinic, a rural outpatient Internal Medicine Clinic, reviewed 1622 records from adults 50-75 years old during the timeframe September 2017 through August 2018. Patients with history of CRC or status-post colectomy for other reasons were excluded from this study. Patient records were assessed for compliance with USPTF CRC screening guidelines. USPTF recommends adults aged 50 to 75 years receive screening as follows: 1) Fecal occult blood testing (FOBT) annually 2) Flexible sigmoidoscopy every 5 years 3) Colonoscopy every 10 years OR 4) Combined FOBT (every 3 years) plus flexible sigmoidoscopy (every 5 years). Results: The review showed that during the timeframe studied, 56% of patients received appropriate screening, 44% were found with no documentation of screening, and 17% were never offered screening or informed about current guidelines. Following data analysis, intervention to increase screening rates has been initiated. This involves provider education, posters in clinic, and individualized letters mailed to patients found deficient during the study. The success of this direct patient outreach effort will be measured over six months. Conclusions: The mortality rate from CRC cancer is higher in Robeson County compared to the NC state rate. Additionally, 40% of deaths from late-stage CRC may be prevented by doing a routine screening. It is the responsibility of providers to emphasize the importance of proper screening. This retrospective review found that a large percentage (44%) of adults are not being adequately screened in our rural clinic. Direct outreach is underway to increase compliance rates in this high-risk population served by our rural clinic.
The results of colorectal cancer screening in the Republic of Kazakhstan during the period from 2013 to 2018.
Authors: Kaidarova Dilyara , Zhylkaydarova Alma , Ukolova Yelena , Jumanov Abay 
Published: May 2019

e13074 Background: Colorectal cancer (CRC) remains one of the actual problems in oncology. In 2017, in the structure of oncopathology of the Republic of Kazakhstan (RK), CRC took the 3rd place in terms of incidence - 17.5, and in mortality - 8.2 per 100 thousand people. The population screening of CRC has been introduced in the Republic of Kazakhstan since 2011, among the population aged 50 to 70 years, with a survey interval every 2 years. Fecal immunochemical test (FIT) and total colonoscopy (TC) were introduced in 2013. Methods: For the period 2013 - 2018, 5133602 subjects were examined. The analysis of screening indicators was carried out: the number of positive results of FIT, completion rate of follow-up colonoscopy and CRC detection rate. The analyzed groups were divided into regions with: A - high (26 - 30.7 per 100 thousand people), B - medium (13.2-21.8), C - low (5.9 - 10.8) incidence. Results: The positive FIT for the study period was found on average, in 1.23% (62971) positive results in the Republic of Kazakhstan, in group A it was 1.50% (27675), in group B - 1.26% (17178), and in group C - 0.94% (18118). The number of TC: in group A - 76.1% (21067), in group B - 75.8% (13016), in group C was 66.7% (12080), in total - 46163 cases in the Republic of Kazakhstan, which is 73.3% of indications. During the period of study 2480 patients with colorectal cancer were identified: in group A - 0.07% (1236), in group B - 0.05% (638), in group C - 0.03% (606) people. Conclusions: For regions with different incidence rates is necessary to define performance indicators to improve the quality assurance in CRC screening.
Features of adolescent and young adult cancer patients in Japan.
Authors: Suzuki Hideo , Aida Yuka , Fukushima Hiroko , Bando Hiroko , Hashimoto Sachie , Ishikawa Eiichi , Muroi Ai , Satoh Toyomi , Shikama Ayumi , Sekine Ikuo 
Published: May 2019

e13081 Background: The number of deaths because of cancer among adolescent and young adults (AYAs) in Japan is about 2,300 per year, which accounts for 17.3% of all deaths in these populations. This study aimed to investigate the clinicopathological features of AYA cancer patients. Methods: Patients registered to the Ibaraki Cancer Registry from our hospital between 2007 and 2017 were included in this study. The proportion of patients by cancer types were calculated by age groups and gender. Results: There were 27281 cancer patients in the registry, among whom, 1972 patients (7.2%) were aged between 15 and 39 years (AYA group) and 2445 were aged between 64 and 66 years (reference group). Female patients were the majority (68.2%) in the AYA group, whereas male patients were the majority (59.7%) in the reference group. Among male patients, central nervous system (22.3%) and germ cell (22.3%) tumors were the most common types in the AYA group, whereas prostate (14.7%) and lung (11.3%) cancers were the dominant ones in the reference group. Among female patients, cervical (35.8%) and breast (14.5%) cancers were the top two cancer types in the AYA group, whereas breast (19.3%) and lung (8.2%) cancers were the dominant ones in the reference group. The proportion of cancer types by 5-year age bands showed three distinctive patterns that could be associated with their etiology. Pattern 1 included central nervous system neoplasm, ovarian cancer, hematopoietic malignancy, bone sarcoma, soft tissue sarcoma, and germ cell tumor, in which the proportion peaked in teenage year group and gradually decreased in the older age groups. Pattern 2 included thyroid, breast, cervix, and uterine cancers, as well as malignant melanoma and lymphoma, which peaked in the twenties and thirties. The other cancer types belonged to pattern 3, in which the proportion increased with age and peaked in the sixties. Conclusions: Cancers in AYAs had a distinctive pattern compared to that in older age patients. The proportion of each cancer by age groups showed three different patterns.
Geographic variation in the incidence of marginal zone lymphoma (MZL) subtypes and infectious risk factors.
Authors: Di Mengyang , Olszewski Adam J. 
Published: May 2019

e13094 Background: Helicobacter pylori is a known etiologic factor for gastric MZL, but data for infectious etiology in other MZL subtypes are controversial. Proposed hypothetical factors include Borrelia burgdorferi for cutaneous MZL (cMZL), Campylobacter (Cmp) for intestinal MZL (iMZL), and hepatitis C (HCV) for splenic (SMZL) or nodal MZL (NMZL). We explored geographic variation in the incidence rate (IR) of MZL and reportable infections in the United States (US) to examine these hypotheses. Methods: Using the National Program of Cancer Registries, we calculated age-adjusted IR (per 100 000 person-years) of MZL subtypes for each US state in 2001-2015. We linked them to the 2010 US census data, data on IR (per 10 000) of Lyme disease (2001-2015) and Cmp infections (2016) from the Center for Disease Control, and to published estimates of HCV prevalence (2013-2016). We examined the hypotheses in multivariable Poisson models adjusting for median age, proportion of men, Black or Asian individuals in each state, reporting adjusted IR ratios (IRR) with 95% confidence intervals (CI). Results: The study included 5,085 cases of cMZL, 3,948 of iMZL, 26,648 of NMZL, and 12,184 of SMZL. Across the US, IR varied between 0.02 and 0.22 for cMZL, 0.04-0.12 for iMZL, 0.33-0.91 for NMZL, and 0.12-0.47 for SMZL. For all subtypes, IR was highest in the Northeast, and lowest in the South ( P<.0001), consistent with general lymphoma epidemiology. However, the IRR for South relative to Northeast was significantly lower for cMZL (0.42; CI, 0.38-0.45) than iMZL (0.65), NMZL (0.65), SMZL (0.67), or aggregate MZL (0.65; CI, 0.64-0.66). In adjusted models, IR of Lyme disease was significantly associated with increased IR of cMZL (IRR=1.11; CI, 1.07-1.16), and Cmp infection was associated with iMZL (IRR=1.19; CI, 1.02-1.38). In contrast, HCV, prevalent in the South, was inversely associated with all MZL subtypes. Conclusions: These results support the putative association between cMZL and Lyme disease, and between iMZL and Cmp infection. Conversely, lack of positive association between any MZL subtype and HCV suggests that it is not a major pathogenic factor in the US. These ecological results do not rule out associations at the individual level, which will require further research.
Metformin, aspirin and statin and risk of cancer: A population-based study in Thailand.
Authors: Oranratnachai Songporn , Phetchoo Piyaporn , Rattanasiri Sasivimol , Thakkinstian Ammarin , Lukerak Somthawin , Vathesatogkit Prin , Sritara Piyamitr , Sirachainan Ekaphop , Reungwetwatttana Thanyanan 
Published: May 2019

e13095 Background: : There were the conflicted results of the association of ASA, metformin or statin and risk of cancer in the previous studies. This is a population-based study in Thai population which aims to investigate the association between these drugs and the risk of cancer. Methods: A population-based retrospective study was done in Electricity Generating Authority of Thailand (EGAT) 1 and 2 databases which have been contained the 27-year and 15-year follow-up time, respectively. This database composed of the clinical characteristics, onset of cancer, and history of interested drugs from the questionnaire, together with the laboratory result from January 2002 to December 2015. We adjusted for age, sex, BMI, smoking and alcohol consumption. The incidence rate ratio (IRR) was estimated for the association between incidence of cancer and interested drugs. Results: Among 2508 and 2731 participants in EGAT1 and 2 respectively, the incidence of cancer was 8.3% in EGAT 1 and 3.5% in EGAT 2. From univariate analysis, use of interested drugs was significant associated with increased risk of cancer with IRR 1.74 ( P< 0.001) for ASA, IRR 1.54 ( P= 0.043) for metformin and IRR 1.64 ( P= 0.001) for statin. In multivariate analysis, only ASA showed significant increasing risk of cancer with IRR 1.47 ( P= 0.021). There was a trend increasing risk of cancer for metformin and statin users but not significant. Older age, low BMI, and female significantly associated with higher risk of cancer. In sub-group analysis, age and alcohol were significantly increased risk of GI cancer, while ASA use showed a non-significant trend of increasing risk of GI cancer. HBV infection was a strongly risk factor for hepatobiliary cancer and statin use had a trend lowering risk of this cancer but it was not statistically significant. Metformin also showed a non-significant trend of increasing risk of thoracic cancer. Conclusions: ASA use significantly associated with increasing risk of cancer but metformin and statin showed a trend of higher risk of cancer. These drugs may associate with cancer metabolome pathway which maybe an important role of carcinogenesis. However, ASA, metformin or statin use and risk of cancer is needed to confirm in the longer follow-up and larger cohort.