bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics in the development of endometrial cancer: How does it affect East Asians?
Authors: Gubernick Lindsay , Lee Jessica , Chern Jing-Yi , Gerber Deanna , Boyd Leslie R. , Curtin John Patrick , Levine Douglas A. , Pothuri Bhavana 
Published: September 2018

e13022 Background: Obesity and Lynch syndrome are well-known risk factors for the development of endometrial cancer. However, there is a paucity of data comparing patients across multiple ethnicities. Methods: All patients diagnosed with endometrial cancer or complex atypical hyperplasia between 2012 and 2015 were retrospectively identified and evaluated. Comparative statistical analyses were performed and stratified by ethnicity with appropriate two-sided statistical tests. Results: A total of 506 patients were diagnosed with endometrial cancer (n = 447) or complex atypical hyperplasia (n = 59) and of these, 31 were East Asian (EA, 6.3%). The remaining 475 patients (93.9%) were of Caucasian, black, Latino, South Asian, Southeast Asian or other unspecified ethnicity. Compared to other patients, EA were diagnosed at a younger age (median age 53 vs 62, p = 0.0003) and had lower body mass indices (BMI) (median BMI 23.0 vs 30.7, p < 0.0001). There were no differences in stage, tumor grade or histology. Differences in age and BMI remained significant despite controlling for these factors on multivariate analysis. Of the EA group, 10 of 31 patients (32.3%) underwent genetic testing and of these, three (30.0%) were found to have a germline mutation in a mismatch repair (MMR) gene. All three patients were of Chinese ancestry, and two had mutations in MLH1 and one in MSH2. In comparison, 69 (14.5%) of the remaining 475 had genetic testing, and six (8.7%) were diagnosed with Lynch syndrome. Chinese patients were more likely to have Lynch syndrome (42.9% vs 8.7%, p= 0.04). There were no differences found in family history of Lynch-related cancers between Chinese and other patients. There was no correlation between germline mutations and MMR testing on tumor immunohistochemistry. All three Chinese patients with Lynch syndrome had negative MMR tumor testing. Conclusions: EA patients with endometrial cancer are diagnosed at younger ages and with lower BMIs compared to patients of other ethnic backgrounds. Chinese patients have a high rate of germline Lynch mutations despite negative tumor MMR testing. EA, particularly Chinese patients, may represent a high-risk cohort, and referral for genetic counseling regardless of tumor MMR testing should be considered.
Do fears of getting cancer and family history of cancer influence participation in opportunistic screening or organized screening for gastric cancer?
Authors: Hahm Myung-Il , Choi Kui Son , Lee Hoo-Yeon , Suh Mina , Lee Yoon Young , Shin Dong Wook , Kim Bokmi 
Published: September 2018

e13045 Background: Cancer is the leading cause of death in Korea. Individuals with a family history of cancer might overestimate their personal risk for getting cancer and report high cancer-related worry or concern. Those factors could positively or negatively influence on cancer screening behavior. Although Korea has a universal screening program for common cancers, some people still choose opportunistic screening program with out-of-pocket costs. This study was to identify association between fears of getting cancer and participation on opportunistic anc organized screening programs for cancer. Methods: The study population was derived from the Korean National Cancer Screening Survey 2013, which is annual survey conducted by National Cancer Center of Korea in order to investigate trends of participation rates among general population in cancer screening. 3,004 individuals aged over 40 years were finally selected as study subjects. Chi-square tests and multinomial logistic regression model were used to identify factors associated with being screened for gastric cancer. Results: A total of 2,078 of the subjects (69.2%) underwent gastric cancer screening, of which 311 individuals (10.4%) participated in opportunistic and 1,767 individuals (58.8%) participated in organized screening programs. After adjusting socio-demographic factors and health behaviors, worry and concern about cancer were identified as factors positively associated with being screened for gastric cancer. ORs for undergoing gastric cancer screening were elevated for both screening programs according to the level of worry and concern about cancer (p for trend < 0.05). We did not found relationship between family history of gastric cancer and participation. Conclusions: The results of this study suggest that fears of getting cancer such as worry and concerned about cancer had a stronger influence on participation in not only organized screening program but also opportunistic screening program. We could identify that ORs for undergoing the opportunistic screening were slightly higher than those for undergoing the organized screening in terms of cancer worry and cancer concern.
Pathologic findings at risk-reducing salpingo-oophorectomy in germline BRCA mutation carriers: Optimal age of bilateral RRSO.
Authors: Kim Yong-Man , Lee Shin-Wha , Lee Young-jae 
Published: September 2018

e13046 Background: Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age of 40. Methods: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2013 to 2015. Both fallopian tubes of all cases were examined according to the SEE/FIM protocol and immunohistochemically (IHC) staining was performed when a precursor lesion was suspected. Results: RRSO was performed in 55 patients. The median age at RRSO was 44 years (32–73 years). Of the 36 patients with IHC staining, 7 showed p53 overexpression, 1 showed Ki-67 overexpression, 2 showed serous tubal intraepithelial carcinoma, 2 showed occult cancer, and 1 showed metastatic cancer of breast origin. All occult invasive cancer cases were tubal origin and detected in patients older than 40 years. The detection rate of premalignant lesions or cancer was 21.8% (12/55). Among patients who underwent RRSO under the age of 40, premalignant lesions were found only in BRCA 1 mutation carriers (40.0% vs 0%). In BRCA 2 mutation carriers, premalignant lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of premalignant lesions in BRCA1 mutation carriers. Conclusions: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers, especially in BRCA 1 mutation carriers.
Age standardized pattern of cancers in Pakistani population from 2008 to 2014.
Authors: Syed Binafsha Manzoor , Mangi Fayaz Hussain , Qureshi Jawaid Naeem , Shaikh Noshad Ahmed , Ujjan Ikram Uddin , Laghari Naeem Ahmed 
Published: September 2018

e13060 Background: Cancer is a heterogeneous disease, influenced largely by gender, genetic makeup and environmental factors. This study was therefore aimed to assess age-standardized pattern in both males and females in Pakistani population. Methods: During the period of seven years (January 2008 to December 2014) prospectively collected institutional data was retrieved. All patients presented with primary cancers were included and pattern of top ten tumors was assessed. The data was analyzed using SPSS 21.0. Results: During the study period, a total of 15,906 patients with primary cancer were reported. Pattern of distribution is given in the table below. Conclusions: Among males and females there has been a different pattern of cancers. However among young males oral cancers remains at the top while lung at the older age and breast cancer among females remains at the high rate regardless of age. [Table: see text]
Anion gap and cancer mortality: Insight from NHANES database.
Authors: Verma Ashish , Qayyum Rehan 
Published: September 2018

e13068 Background: The serum anion gap is an effective tool to analyze acid- base disorders for the past 40 years. Anion gap and non-anion gap acidosis is prevalent in cancer patients and contributes to morbidity and mortality The aim of the present study was to investigate the independent association of serum anion gap with cancer mortality. Methods: We examined the 34,370 participants ( ≥ 20years of age) using National Health and Nutrition Examination survey data (1999-2010) combined with National Death Index for mortality status through December 2011.The serum anion gap was calculated by subtracting sum of chloride and bicarbonate from sodium concentrations in meq/l. We divided the data set in to four quartiles of serum anion gap. Cox proportional hazard models were made to estimate the hazard ratios for cancer mortality for each unit increase in serum anion gap. The models were adjusted from demographic and confoundig variables. Results: The mean age of participants was 49.59±18.42 years. Out of total population 33,717(98.1%) were alive and 651 (1.9%) were dead secondary to cancer. The mean period of follow up was 5.55±3.53 years. In univariate regression model using serum anion gap as continuous variable, we found 6% (HR-1.06;95%CI,1.0-1.1), increase in cancer mortality with each unit increase in serum anion gap. After adjusting for potential confounders using multivariate regression model we found 8%(HR-1.08;95%CI,1.03-1.14), increase in cancer mortality with each unit increase in serum anion gap. In univariate regression model using quartiles, we found 47% (HR-1.47;95%CI,1.04-1.93), increase in cancer mortality with each unit increase in serum anion gap in highest quartile compared to the lowest quartile. After adjusting to the potential confounders the risk for cancer mortality increases to 60% in highest quartile comparison to lowest quartile (HR-1.60;95%CI,1.12-2.26). Conclusions: We found a linear association between serum anion gap and cancer mortality. A high serum anion gap is associated with increase in cancer mortality and may be the prognostic indicator of cancer mortality in general population. This should be validated by performing further investigation.
Breast cancer in Angola, molecular subtypes: The first preliminary study.
Authors: Santos Lúcio Lara , Miguel Fernando , Lopes Lygia Vieira , Oliveira Julio , Ferreira Eduardo , Lopes Carlos 
Published: September 2018

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.
Tissue trauma and the subsequent risk of soft tissue sarcoma of the extremity: A population based case-control study in Sweden.
Authors: Olsson Hakan Lars , Wagner Philippe 
Published: September 2018

e13088 Background: Soft tissue sarcomas (STS) are a rare group of heterogeneous tumors that may occur in the extremities. Little is known of their etiologies and only a handful putative risk factors have been identified. Studies as well as case reports have connected soft tissue tumors to events of physical trauma. There is mounting evidence of inflammation as both an initiator and promotor of tumorigenesis, as well progression. Moreover, as the physiological response of tissue repair and regeneration is mediated through inflammation, it is not unlikely that physical injury may cause and/or contribute to tumor initiation, promotion and/or progression, not least when the subsequent inflammation becomes chronic. Methods: We conducted a matched case control study in a total population in the South of Sweden 1988-2009, collecting 249 cases to examine the risk of STS of the extremities (STSE) following exposure to physical trauma such as accidental injury and/or surgery. Results: Having been exposed to surgery or injury from accidents to any part of the body both increased the risk of STSE, OR 2.1 (1.5 – 3) and 1.5 (1.1 – 2.1), respectively. Adjusting for potential confounders yielded ORs of 2.4 (1.6 – 3.6) and 1.4 (1.00 – 2.00). Surgery related odds ratios (SOR) varied with STSE histological subtype, from 1.2 to 4.2. UPS/MFH, Leiomyosarcoma and Liposarcoma showed significantly elevated SORs that were significantly greater than for remaining subtypes (P = 0.029). The accident related odds ratio (AOR) varied from 0.8 to 3.5, being significantly elevated for Leiomyo- and Liposarcoma, and the AOR of the two combined was significantly greater than remaining subtypes (P = 0.045). Analyzing surgery or accidental injury to a given part of the body and the subsequent STSE risk in the same location showed the SOR to be 4.13 (1.87 – 9.15) and the AOR was 2.29 (1.21 – 4.32). Conclusions: The population attributable risk of having had surgery was 37% (20 – 53%) and accidental injury was 13% (2 – 24%). Combined, the PAR was 43% (25 – 57%), indicating that tissue trauma may be an important contributing factor in sarcomagenesis of the extremities.
Prevalence of germline TP53 p.R337H mutation in Brazilian young breast cancer patients.
Authors: Fortes Fernanda Paschoal , Tonhosolo Renata , Jbili Rima , Santiago Karina Miranda , Andrade Kelvin , Nobrega Amanda Franca , Achatz Maria Isabel Isabel 
Published: September 2018

e13101 Background: Germline TP53 mutations are associated with Li-Fraumeni syndrome (LFS), a disease that predisposes carriers to a wide variety of early onset tumors. Pre-menopausal breast cancer is the most frequent tumor found in carriers. In Southern and Southeastern Brazil, a germline TP53 mutation in exon 10, p.R337H, was diagnosed in 0,3% of the population due to a founder effect, a prevalence that is substantially higher than other LFS mutations. Methods: In this study we investigated the prevalence of the p.R337H TP53 germline mutation in 287 young female breast cancer patients (diagnosed before the age of 40) at A. C. Camargo Cancer Center, Sao Paulo, Brazil. DNA was extracted from saliva and Sanger sequencing of exon 10 was performed. All patients were consented. Results: The p.R337H TP53 mutation was present in 1.74% (5/287). Family history of cancer was present in three cases although it did not fulfill LFS clinical criteria. Conclusions: The identification of germline p.R337H mutation in this cohort strengthen the role of TP53 mutations in the early onset of breast cancer in pre-menopausal cancer in Brazil.
Clinical implementation of a comprehensive targeted amplicon sequencing system for cancer in Japan.
Authors: Hayashi Hideyuki , Tanishima Shigeki , Mori Ryo , Okamura Yasunobu , Amano Toraji , Kinoshita Ichiro , Komatsu Yoshito , Akita Hirotoshi , Nishihara Hiroshi 
Published: September 2018

e13115 Background: The development of clinical sequence systems in hospitals is a critical issue in Japan, especially for medical oncology, as multiplex gene profiling enables precision medicine for cancer. We have launched an in-house clinical sequencing system,“CLHURC” to perform exhaustive targeted exome sequencing for patients with all types of cancer, as an outpatient service. We have analyzed the clinical utility of this system. Methods: Genomic DNA was extracted from tumor tissues and peripheral blood sera of 81 patients with different stages of cancer, during April-December 2016. The top five types of primary cancer were pancreas (16%), colorectal (16%), breast (10%), stomach (9%), and lung (6%). We performed a targeted amplicon exome sequencing for 160 cancer-related genes. The sequencing data was analyzed using an original bioinformatics pipeline within three days, and we identified cancer-specific somatic gene alterations such as SNV (Single Nucleotide Variation), Ins (Insertion)/Del (Deletion), and CNV (Copy Number Variation). The primary endpoints were the detection rates of potential actionable and druggable genes. The secondary endpoints were the detection rates of incidental germline variants and the period from initial visit to elucidation of the results to the patients. Results: Actionable and druggable gene alterations were detected in 90% (73/81) and 51% (41/81) of the subjects, respectively. Druggable gene alterations were frequently detected in BRCA1/2 (11/41), PIK3CA (9/41), AKT1/2 (6/41), TSC1 (5/41), and PTEN (5/41). Surprisingly, incidental germline variants were detected in 31% (25/81) of the patients, and were found in BRCA1/2 (5/25), APC (5/25), and TSC1(3/25), among others. The median period of examination was 21 days (10-66 days). Twelve out of the 81 patients (15%) were treated with therapeutic agents, based on the results of our clinical sequencing. Conclusions: We have established a robust in-house clinical sequencing system, “CLHURC,” and have initiated the development of precision medicine for cancer in Japan. Our novel clinical sequencing system could improve individualized medicine against cancer throughout Japan and Asia.
AWARE: Randomized study of an EMR-based intervention targeting hereditary cancer (CA) risk awareness in peri-op CA patients (pts).
Authors: Hall Michael J. , Handorf Elizabeth , Chertock Yana , Keleher Cindy A , Siemon Mark , Rubin Stephen C. , Sigurdson Elin R. , Uzzo Robert , Savage Michelle , Daly Mary Beryl 
Published: September 2018

e13119 Background: Pts having CA surgery have high information needs related to diagnosis, stage, and what caused their CA. Direct EMR access via web portals has grown, and offers a novel means to integrate supplemental health information into the e-chart, such as relevant genetic risk of CA. The AWARE trial (Advancing Web-based Medical Record Access and Risk Evaluation for Cancer Patients) studied the impact of providing personalized pathology (pPATH) and pers/fam history (PFHx) summaries enhanced with information about genetic CA risk and risk assessment. Methods: Peri-op CA pts completed baseline and 3-mo follow-up surveys. Pts randomized to enhanced (E) arm received pPATH & PFHx summaries with embedded tailored info about genetic CA risk and relevant high-risk features. Unenhanced (U) arm got pPATH & PFHx only. Use of summaries and 2 “Genetic risk: Learn more” links was tracked. Outcomes-Primary: awareness, knowledge (of genetic CA risk); Secondary: perceived risk, use of “Learn more” links, intentions/actions toward risk assessment--were stratified by genetic risk factors reported at baseline (0-1, 2+) & use of “Learn more” links. Results: 171 pts consented; men (p = 0.003) & non-White (p = 0.02) were more likely to decline the study. Overall 149 (87%) were randomized & eligible to use AWARE: 109 (73%) logged in, 120 (81%) completed follow-up. Predictors of AWARE use: White race (p < 0.05), sib w/CA (p < 0.05), and use intention (p = 0.005). Reporting 2+ genetic risk factors at baseline predicted use of pPATH, PFHx, and “Learn more” (all p < 0.001). Awareness increased overall (p < 0.002), but between arm changes in primary outcomes were not significant. E arm (vs U) was borderline more likely to seek risk assessment (32% v 18%, p = 0.09), with impact stronger in pts reporting baseline 0-1 (p = 0.035) vs 2+ risk factors (p = 0.7). Among E arm pts who used “Learn more” links, intentions (p = 0.054) & behaviors (p = 0.035) to seek risk assessment increased. Conclusions: AWARE increased genetic risk awareness overall, but primary outcomes were not met. Usage data and secondary outcomes highlight potential for EMR-based interventions to positively impact preventive behaviors toward genetic risk assessment.
TG6002: A novel oncolytic and vectorized gene pro-drug therapy approach to treat glioblastoma.
Authors: Idbaih Ahmed , Erbs Philippe , Foloppe Johann , Chneiweiss Hervé , Kempf Juliette , Homerin Michel , Schmitt Charlotte , Nguyen Them Ludovic , Delattre Jean-Yves 
Published: September 2018

e13510 Background: Glioblastoma (GBM) is an incurable disease challenging innovations for significant therapeutic progress. TG6002 is a vaccinia virus that replicates mainly in tumor cells after deletion of genes coding for thymidine kinase and ribonucleotide reductase. TG6002 alsoexpresses the yeast-originated gene FCU1 encoding cytosine deaminase and uracilphosphoribosyltransferase that transforms the pro-drug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluoro-uridilyl monophosphate (5-FUMP), respectively. The proof of this ‘suicide gene’ concept has been demonstrated in man, using a non-replicative vaccinia virus hosting the FCU1gene (Husseini F et al, ASCO 2012). TG6002 mechanism of action then associates oncolysis of tumor cells, immune reaction against released tumor antigens and local chemotherapy. Methods: Prior to initiating clinical development, the anti-tumor activity of the TG6002/5-FC combination was investigated, using U-87MG human GBM cell line and patient-derived cell lines (PDCL). Results: The growth of U-87MG subcutaneous tumors implanted in nude mice was inhibited by systemic administration of TG6002 with or without 5-FC. Mice treated with TG6002 only survived significantly longer than controls; this survival benefit was not modified by addition of 5-FC to TG6002. In contrast, in an orthotopic brain tumor model, mice survived significantly longer when treated intravenously by TG6002 alone, and oral 5-FC added a significant survival benefit. In this model, TG6002 was found in the brain of xenografted mice but not in that of control mice without tumor, indicating a tumor-specific replication of TG6002. PDCL were also exposed in vitro to TG6002. Evidences of virus replication and tumor cells death were detected. In addition, TG6002 exhibited a synergistic cytotoxic effect when combined with temozolomide in this model, suggesting a potential interest for clinical development of this combination. Conclusions: Taken together, our results support initiation, in recurrent GBM patients, of a phase 1 clinical trial testing TG6002 safety in combination with 5-FC, as a first step toward investigation of clinical efficacy of this therapeutic combination in GBM.