bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative risks of prostate cancer associated with different family cancer histories.
Authors: Beebe-Dimmer Jennifer Lynn , Kapron Ashley , Fraser Alison M , Smith Ken R , Cooney Kathleen A. 
Published: May 2019

1505 Background: Recently developed clinical guidelines have suggested that men in families with Hereditary Prostate Cancer (HPC), Hereditary Breast and Ovarian Cancer (HBOC), and Lynch Syndrome (LS) be referred for consideration of genetic testing, especially in the setting of aggressive disease. However, while a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of risk associated with specific FH, and particularly with respect to known familial cancer syndromes, in a single population is needed. Methods: The Utah Population Database was used to identify 569,320 men, 40+ years with a pedigree that included at least three consecutive generations. Each man was evaluated for FH of FPC, HPC, HBOC and LS, as well as their own PC status. PC cases (N=34,889) were identified from both the SEER Utah Cancer Registry and death certificates and classified into one or more subtypes: early-onset (EO [age of diagnosis <60 years]), lethal, and/or aggressive (Gleason Grade ≥7, metastatic, or lethal). Relative risks (RR) associated with each PC subtype, adjusted for important covariates, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding confidence intervals (CIs) for each FH definition. Results: A FH of HPC conveyed the greatest relative risk for all PC subtypes (RR=2.30; 95% CI 2.21-2.39), followed by HBOC and LS. Furthermore, the strongest risks associated with FH were generally observed for EO disease. No differences in risk by degree of FH were observed for either lethal or aggressive disease. Conclusions: In this large population-based family database, the risk of PC was shown to vary by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance. [Table: see text]
Clonal hematopoiesis of indeterminate potential (CHIP) mutations in solid tumor malignancies.
Authors: Conces Madison , Ni Ying , Bazeley Peter , Patel Bhumika , Funchain Pauline , Carraway Hetty E 
Published: May 2019

1507 Background: CHIP predisposes to a higher risk of developing hematological malignancies and cardiac events. Multiple germline mutations have been recognized as contributing to CHIP, most notably ASXL1, DNMT3A, and TET2. The frequency of CHIP mutations in solid tumor malignancies (STM) is unknown. We report the frequency and incidence of CHIP mutations in adult patients (pts) with STM. Methods: Data from 880 pts with STM who underwent next generation sequencing (NGS) at Foundation One from 2013-2017 was collected. This excluded two pts with known primary hematological malignancies who were removed. A list of CHIP mutations using NCCN guidelines as well as numerous original research articles was created, and tabulation of pathogenic or likely pathogenic mutations ( ASXL1, DNMT3A, TET2, JAK2, SF3B1, TP53, GNAS, N/KRAS) was performed. To date, only the lung, breast, and colorectal cancer pts have been annotated (N = 372) since these cancers have an overall higher incidence and prevalence in society. Results: Annotation of lung cancer pts (155/880), breast (118/880), and colorectal cancer pts (99/880) is collected and represents about 40% of all pts. At least one CHIP mutation was present in 44.5% (69/155) lung cancer pts, 32.2% (38/118) in breast cancer pts, and 7.1% (7/99) in colorectal cancer pts. Most common mutations found were TP53 and KRAS at 29.6% (110/372) and 28.0% (104/372), respectively. Mutations in genes not known to be somatic drivers for solid tumor malignancies, particularly SF3B1, DNMT3A, and JAK2, were found at very low frequencies 0.8% (3/372), 0.5% (2/372), and 0.3% (1/372), respectively. Notably, ASXL1 and TET2 mutations were not encountered in any pts. Conclusions: In tumor NGS testing, multiple CHIP mutations were noted to be present within the cohort of lung, breast, and colorectal cancers. There is a need to further understand clinical consequences of CHIP mutations incidentally found in pts with STM given known clinical implications of CHIP. We will report on clinical data (comorbidities), response/non-response to therapy, and identify specific molecular patterns of mutations to further understand the role of CHIP in pts with STM.
Antiviral therapy to reduce hepatocellular carcinoma recurrence in patients with low HBV-DNA levels: A randomized controlled trial.
Authors: Huang Gang , Li Peng-Peng , Lau Wan Yee , Pan Ze-Ya , Zhao Ling-Hao , Wang Zhen-Guang , Wang Meng-Chao , Zhou Wei-Ping 
Published: May 2019

1510 Background: Despite antiviral treatment has been shown to reduce hepato- cellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. Methods: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were ran- domly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. Results: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P 1/4 0.016, P 1/4 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409– 0.884; P 1/4 0.010] and 0.509 (95% CI, 0.333–0.778; P 1/4 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recur- rence (hazard ratio [HR] 1/4 0.316, 95% CI 0.157 – 0.637; P 1/4 0.001) but not of early tumor recurrence (HR 1/4 0.782, 95% CI, 0.493–1.240; P 1/4 0.296). Conclusions: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection. Clinical trial information: ChiCTR-IPR-15006587.
Adequacy of self-reported family history in electronic health record for genetic risk assessment for Lynch syndrome.
Authors: Pande Mala , Okon Connie , You Y. Nancy , Peterson Susan K. , Arun Banu , Lynch Patrick M. 
Published: May 2019

1515 Background: Self-reported family cancer history (FCH) is one of the key indicators of hereditary cancer risk. Studies have shown that accurate FCH documentation by healthcare providers is suboptimal, but data regarding patient-provided FCH are limited. We evaluated the quality of FCH as entered by the patient into the electronic health record (EHR) to determine its adequacy for Lynch syndrome (LS) risk assessment. Methods: At our tertiary referral cancer center, FCH is self-reported via an online questionnaire sent prior to appointment, which is reviewed/updated by clinic nurse during initial visit and then imported into EHR review of systems. Records of all new patients from September 2016 to August 2017 were retrospectively reviewed and analyzed. FCH quality was estimated by calculating rates of reporting of 3 FCH variables required for PREMM5, a risk-prediction model for LS. Parameters required for the model were sex, age, personal history of cancer, and for FCH, degree of kinship (first/second degree), cancer site/type, and age at diagnosis. Results: Of 47,647 unique patients, 47.5% reported FCH for 1 or more relative (46.1% were first degree, 64.8% second degree, 3.0% other, and 2.4% missing). A cancer type/site was specified for 88.8% reporting FCH. Age at diagnosis was listed for 21.7% of the relatives’ cancers. Overall, only 20.9% provided all 3 FCH data elements required for running PREMM5 (9.9% of the total sample, n=4738). Fewer men (9.5%) than women (28.1%) provided all 3 FCH elements. Furthermore, 46.7% of breast cancer patients, 21.9% of gastrointestinal cancer patients, 47.2% and 23.1% of patients seen for cancer prevention screening and endoscopy respectively, reported 3 FCH elements. Lower rates were observed for other cancers. Conclusions: Patient self-reported FCH is suboptimal for estimation of LS risk and genetic counseling referral. Future steps to optimize online patient-facing FCH collection to enable routine automated risk-assessment in an essentially provider-free setting may include, patient education regarding importance of FCH, EHR prompts for FCH completion, and implementation of algorithms in EHRs using FCH to identify patients at risk for hereditary cancer predisposition syndromes.
Preventive surgery after multiplex genetic panel testing (MGPT).
Authors: Idos Gregory , Kurian Allison W. , Ricker Charité , Sturgeon Duveen , Culver Julie , Kingham Kerry , Koff Rachel , Chun Nicolette M. , Rowe-Teeter Courtney , Levonian Peter , Hong Christine , Mills Meredith , Ma Cindy , Lancaster Johnathan M. , Brown Krystal , Kidd John , McDonnell Kevin , Ladabaum Uri , Ford James M. , Gruber Stephen B. 
Published: May 2019

1525 Background: Guidelines recommend consideration of prophylactic surgery for patients with a germline pathogenic variant in some cancer predisposition genes. We assessed surgery utilization in a prospective, multi-institutional cohort study of MGPT. Methods: 2000 patients had MGPT and completed questionnaires at 3, 6, and 12 months. Patients reported surgical utilization and indication (treatment or prevention). Surgery utilization was assessed according to cancer history and MGPT test results: Positive, pathogenic variant; VUS, variant of uncertain significance; Negative, benign variants. Results: Overall, 12.9% (198/1537) of patients reported surgery after MGPT (median follow-up 13 months). Only 31.3% (62/198) of patients specified that their surgery was preventive. Preventive surgery utilization was significantly higher among patients who tested positive (n=30, 14.9%) compared to those testing negative (n=20, 2.3%, p<0.001) or VUS (n=12, 2.2%, p<0.001). Preventive surgery was very low among patients testing negative or VUS who had no personal history of cancer in the relevant organ (Table). For example, mastectomy was not reported among any patients testing negative or VUS who had no personal history of breast cancer (Table). Conclusions: More than one year after MGPT, prophylactic surgery use was low among patients with VUS or negative results, especially among those with no personal history of cancer at the relevant site. Surgery utilization. [Table: see text]
Germline variants in urothelial carcinoma: Analysis of pathogenic and likely pathogenic variants in 645 subjects.
Authors: Abou Alaiwi Sarah , Nassar Amin , Mouw Kent William , Kwiatkowski David J. , Choueiri Toni K. , Curran Catherine , Van Allen Eliezer Mendel , Esplin Edward D. , Yang Shan , Garber Judy Ellen , Rana Huma Q. , Sonpavde Guru 
Published: May 2019

1528 Background: While small studies have supported a genetic cancer predisposition among subjects with urothelial carcinoma (UC), systematic germline evaluation of this population is lacking. Here, we report the prevalence of germline variants among subjects with UC from multiple centers completing panel-based testing at a large, commercial laboratory. Methods: 1149 UC subjects underwent germline testing of 1 to 126 genes using massively parallel sequencing with customized capture bait-sets to analyze exonic regions, flanking intronic sequences, and copy number alterations. Pathogenic (P) and likely pathogenic (LP) were confirmed using orthogonal technology in accordance with Invitae standard operating practices. Analysis was limited to 645 subjects who completed testing of a shared set of 42 genes. P/LP variants including single nucleotide variants/indels/ copy number variants are reported. De-identified personal and family cancer histories were evaluated. Fisher’s Exact test and the Mann-Whitney test were used to analyze categorical and continuous variables respectively. Results: Among the 645 UC subjects with 42-gene testing for any indication, median age at testing was 60 years (6-88) and 326 (51%) were female. P/LP variants were identified in 21 (50%) of the 42 genes in 98 (15%) of subjects, including Lynch syndrome genes (n = 26 [4%]), BRCA1/2 (n = 16 [2.5%]), CHEK2 (n = 15 [2.3%]), and heterozygous MUTYH (n = 12 [1.9%]). Among 18 DNA damage repair (DDR) genes assessed, 90 P/LP variants were detected in 88 subjects (12.2%). There was no significant association between presence of a DDR gene variant and age at diagnosis, gender or reported family history of UC in a first degree relative (n = 48). Among subjects with documented history of UC only without other cancers (n = 195), 24 (12.3%) had P/ LP variants, of which 23 (11.8%) were in a DDR gene. Conclusions: Germline P/LP variants were identified in 15% of UC subjects most of which (92%) were in DDR genes, including 27% in Lynch syndrome genes. PARP and T-cell checkpoint inhibitors may warrant evaluation in subjects with germline DDR mutations. Further validation in unselected UC pts is warranted to propose examining germline P/LP variants in all UC patients.
Prognosis value of a genetic score based on germline genetic variants in a prospective cohort of early triple-negative breast cancer patients.
Authors: Curtit Elsa , Henriques Julie , Paget-Bailly Sophie , Ladoire Sylvain , Darut-Jouve Ariane , Debled Marc , Romieu Gilles , Garnier-Tixidre Claire , Jacquin Jean-Philippe , Soulie Patrick , Jouannaud Christelle , Rios Maria , Petit Thierry , Bachelot Thomas Denis , Faure-Mercier Céline , Gambotti Laetitia , Blanché Hélène , Deleuze Jean-Francois , Cox David , Pivot Xavier 
Published: May 2019

1529 Background: Triple-negative breast cancers (TNBC) are a heterogeneous group of tumors with poor outcome. In this study, the association between germline genetic variants and invasive disease-free survival (iDFS) was analyzed in TNBC patients. Methods: A genome wide-association study (GWAS) aimed to identify variants (single nucleotide polymorphisms – SNPs) associated with prognosis in 1121 patients with TNBC in the SIGNAL prospective cohort. Associations between gene variants and iDFS were assessed in univariate Cox regression models. Variants were combined in a score to identify risk categories. A prognostic model based on breast cancer stage and genetic variants was estimated using a multivariate Cox regression. Interaction between stage and genetic score was tested. Discrimination of the model was assessed by the Harrell’s C statistic and internal validity by bootstrap method. Results: The characteristics of the 1121 patients were representative of a population with early TNBC. Four SNPs on chromosomes 9 and 2 were found significantly associated to iDFS in univariate Cox models. Homozygous status for the most frequent allele was associated with poorer iDFS for two SNPs and this status was present in 50% and 57% of the population. For the two other SNPs, the most frequent allele was associated with more favorable iDFS. Three prognostic categories were derived from the genetic score. The following table presents the results from the multivariate Cox model including genetic score and disease stage. Clinical trial information: RECF1098. Conclusions: In a prospective cohort of 1121 patients with early TNBC, 4 genetic variants (SNPs) were associated with iDFS. A score involving SNPs provided similar prognostic indications as breast cancer stages. A search assessing the function and the role of the involved genes is ongoing.[Table: see text]
Test of InheRET, an online tool to facilitate NCCN Guideline compliant referrals for cancer genetic counseling.
Authors: McCain Lynn , Milliron Kara J. , Cook Amanda , Schroeder Lee , Arthurs James , Harper Diane M , Ernst Susan , Zazove Philip , Parvaz Jasmine Diana , Keren David , Merajver Sofia 
Published: May 2019

1530 Background: Identifying the ~60 million unaffected persons in the US at risk for inherited cancers has the potential to reduce their cancer risk by up to 95%. However, most of these individuals are not identified currently because of multifactorial deficits in the 3-generation pedigree collection in clinical settings. Methods: Here we evaluated the impact InheRET, an online family history gathering and risk assessment reporting tool, has on facilitating National Comprehensive Cancer Network (NCCN) Guideline-compliant referrals for cancer genetic counseling/genetic evaluation by decreasing and/or removing the barriers of 1) in-clinic 3-generation family history collection, and 2) interpretation of the family and personal history in light of current NCCN Guidelines. Patients enrolled from primary care and specialty clinics completed the family health history from a web-enabled devices using InheRET Inherited Risk Evaluation Tool. Results: Of 255 enrolled patients, 78.4% completed the history form and, of these, 86.5% completed the feedback survey. 39.2% of primary care and 79.9% of specialty cancer genetics patients were found to be at increased risk. Patients with ≤ HS education ranked InheRET at 4.7/5.0 for Understandability and 3.33/5.0 for Ease of Use. Following the addition of clarifying directions, they ranked InheRET at 5.0 and 4.0, respectively. Pts. <60 ranked InheRET between 3.5 and 3.8 on Ease of Use, while those 60-69 and 70+ ranked it 3.0 and 2.7, respectively, potentially reflective of lower technical skills. Age did not impact Understandability. In the cancer genetics clinic, 86% of pts. completed the online survey, in ~ 1 week, compared to paper forms, which required reminders, and >4 weeks to obtain. Conclusions: In this pilot, InheRET accelerated appropriate referrals and efficient utilization of genetic counseling services; improvements to navigation are being implemented prior to dissemination.
Effectiveness of low-dose CT scan for lung cancer screening in the community setting.
Authors: Mouabbi Jason Aboudi , Hadid Tarik H. , Uh Eugene 
Published: May 2019

1543 Background: Lung cancer is the leading cause of cancer death in the United States (US) and worldwide. Chest X-ray (CXR) is ineffective in reducing lung cancer mortality. National Lung Cancer Screening Trail (NLST) reported 20% reduction in mortality with the use of low-dose computed tomography (LDCT) scan to screen high risk individuals. Therefore, major organizations including US Preventive Services Task Force has adopted LDCT for lung cancer screening in high risk populations. However, The generalizability of this approach in community setting is yet to be confirmed. Our objective is to assess the ability of LDCT in detection of lung nodules and lung cancer in the community setting and compare the results to those reported in the NLST. Methods: Charts of subjects who underwent LDCT screening between 2013 and 2016 at SJHMC were retrospectively reviewed. Demographic data, the results of the LDCT scans, interventions performed, complications of procedures and pathology findings were collected. All cancer cases found by LDCT and the stage of cancers were documented. The results of our study were statistically compared to the results of both arms of the NLST (CT and CXR arms). Since CXR is ineffective for lung cancer screening, CXR arm serves equivalently to no screening. Results: The baseline characteristics of the subjects are significantly different between this study and NLST. LDCT in our study detected significantly higher positive findings. There are more cancers detected in this study compared to NLST CT and CXR arms, which could reflect higher incidence of cancer in this community or higher proportion of current smokers in our study. In this study, LDCT detected cancers at higher stages compared to that of the NLST CT arm but similar stages to NLST CXR arm. This may indicate that LDCT when performed in the community is less effective in detecting cancer at early stages. Conclusions: The community population have different characteristics compared those enrolled in clinical trials. This may limit the generalizability of the results. Population-based studies are needed to confirm the results of the NLST. [Table: see text]
A comparison of risk factors for cigarette and e-cigarette use in the United States adult population.
Authors: Chen Leo , Wang Nai Wen , Cheung Winson Y. 
Published: May 2019

1546 Background: The US CDC and public health agencies have reported alarming increases in e-cigarette (ecig) use among youth, even as cigarette (cig) use among youth decline. In this study, other risk factors for cig and ecig use are compared. Methods: This study used data from the Health Information National Trends Survey 5 Cycle 1 survey, conducted in 2017. Univariate survey-weighted logistic regression analyzed responses as a nationally representative US population. Results: Inverted trends included being 35 or older (cig: OR=1.22, p<0.01; ecig: OR=0.79, p<0.01), being a student (cig: OR=0.77, p<0.01; ecig: OR=1.24, p<0.01) or retired (cig: OR=1.09, p<0.01; ecig: OR=0.89, p<0.01) compared to being employed, and being single (cig: OR=0.92, p<0.03; ecig: OR=1.18, p<0.01). Having considered quitting smoking was not significantly associated with ecig use. Conclusions: Segments of the US adult population educated with anti-tobacco campaigns may remain at increased risk for ecig use.[Table: see text]