bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic characterization in gastrointestinal cancer patients based on cfDNA sequencing.
Authors: Wang Minghua , Zheng Zhi , Wang Zhouyang , Cheng Shaochen , Chen Yaru , Liu Yuanyuan , Ren Xiaojing 
Published: June 2023

e15507 Background: Gastrointestinal cancer (GIC) is one of the most prevalent cancers worldwide. Late stages diagnosis is one of the main reasons for poor prognosis of GIC. The invasive nature of endoscopy assay has greatly decrease the willingness for early screening, nearly 50% of patients diagnosed with GIC were in advanced stages. With the advanced of next-generation sequencing (NGS) technology, liquid biopsy has quickly gaining interest in early cancer screening. In order to address the poor prognosis of GIC, mutation features and potential biomarkers were investigated using NGS data from 169 Chinese GIC patients with blood derived cell-free DNA (cfDNA). Methods: Blood-derived cfDNA sampels were collected from Chinese patients with colorectal cancer (CRC) (n = 121) and gastric cancer (GC) (n = 48) and then performed pan-cancer sequencing panel targeting 680 cancer-related genes. Genomic alterations of single nucleotide variations, short indels and tumor mutation burden were analyzed. Two-sided Fisher’s exact test was used for all statistical analyses. COSMIC data was retrieved from COSMIC database version 97. Results: Among GC patients, the proportion of patients possessing mutations in TP53 (43.75% vs 37%, p = 0.49) and KRAS (10.42% vs 5.6%, p = 0.19) showed consistent distribution with COSMIC database. While KIT (14.58% vs 3.42%, p = 0.0014) and SYNE1 (10.42% vs 30.8%, p = 0.0021) showed varied distribution outcomes. CRC patient cohort also showed coherent distribution compared with COSMIC database. No significant difference was detected between the two cohorts in TP53 (51.5% vs 44.57%, p = 0.085), KRAS (36.53% vs 32.33%, p = 0.24), APC (44.91% vs 47.74%, p = 0.48) and PIK3CA (14.37% vs 14.10%, p = 0.91). However, the proportion of SYNE1 mutation is still significantly lower than in the COSMIC database (17.37% vs 29.31%, p = 0.0006). As all patients from the study cohort are Chinese, whether a lowered occurrence of SYNE1 mutation is specific to Chinese or certain region can be further studied. Conclusions: This study revealed that the mutational landscape of liquid biopsy cfDNA sequencing is highly consistent with existing database, which has consolidated the feasibility of liquid biopsy in early cancer detection. Besides, this study also revealed a lowered occurrence of SYNE1 and increased KIT mutation in the cohort. While increased KIT mutation can be explained by the proportion of recruited gastrointestinal stromal tumor patients, the lowered SYNE1 can provide new insights into region-specific diagnosis and treatment selection.
Prevalence of hypertension, hyperlipidemia and diabetes in colon cancer patients and its impact on physical health and quality of life reported in the All of Us research program.
Authors: Osei Noah , Eun Yong , Mohamed Salih Rajaa , Olusoji Rahman Adesoji , Ahluwalia Meena 
Published: June 2023

e15515 Background: The NIH All of Us research program is a prospective, nationwide cohort study currently enrolling more than 594,000 people in the United States. Chronic diseases such as hypertension (HTN), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD) are associated with increased morbidity and mortality in cancer patients. Few studies have assessed the impact of each illness on colon cancer patients using extensive population data in the United States. In this study, we investigate the prevalence of these disorders in colon cancer patients and how they affect physical health and quality of life using the All of Us research database. Methods: In this cross-sectional study, we included participants from All of Us dataset version 6, which includes data collected between May 6, 2018, and January 1, 2022, who had available electronic health records (EHR) data. We identified individuals with colon cancer using the ICD-9/ICD-10 diagnosis code and then examined the presence of three disease conditions from the EHR data. Each disease's prevalence and odds ratio were calculated among colon cancer patients (N = 2,366) compared to all participants with available EHR data (N = 258,188). Responses to two questions (perception of overall physical health and quality of life) were studied with options scored from 1 (Poor) to 5 (Excellent). We compared the mean scores between colon cancer patients and colon cancer patients with HLD (N = 1,254), T2DM (N = 356), and HTN (N = 1,234). The odds ratio was calculated using unconditional maximum likelihood estimation. The study compared scores using the Wilcoxon rank sum test, with a significance level of P < 0.05. Analysis was performed in the web-based platform Jupyter Notebook using the programming language R. Results: The prevalence of HTN, HLD, and T2DM in participants with colon cancer was 52.3%, 53.0%, and 15.1%, respectively, compared to 21.6%, 22%, and 7.9% in all participants. The calculated odds ratio of HTN, HLD, and T2DM in participants with colon cancer was 4.05 (95% confidence interval: 3.74-4.40), 4.06 (3.74-4.41), and 2.08 (1.86-2.33), respectively. Mean scores of physical health and quality of life were significantly lower in colon cancer with T2DM patients compared to colon cancer patients. However, the scores of participants with colon cancer and HLD or colon cancer and HTN were not significantly different from participants with colon cancer. Conclusions: Our analysis shows that individuals with colon cancer have a higher prevalence of HTN, T2DM, and HLD than all participants in the All of Us database. T2DM in colon cancer patients is associated with poor self-reported physical health and quality of life. This highlights the importance of regular screening and optimal control and management of chronic disorders in patients with colon cancer.
The risk of cerebrovascular accidents in colon cancer in the United States: A population-based national study.
Authors: Alkrekshi Akram , Al Armashi Abdul Rahman , Elantably Dina , Wang Jiasheng , Hammad Faris , Al Zubaidi Anas , Brell Joanna M. 
Published: June 2023

e15516 Background: Colon cancer is the 3rd most common cause of cancer death in the United States. However, death rates have been decreasing due to increased uptake of screening and advances in treatment; as a result, there are more than 1.5 million survivors. In addition, cancer as a risk for venous thromboembolism (VTE) is established, and the underlying mechanisms of VTE are shared with arterial thromboembolism. Yet, there is a lack of population-based data to define the risk of cerebrovascular accidents (CVA) in colon cancer. Methods: Retrospectively we analyzed data from a nationwide commercial database (Explorys, IBM) from 1999 to October 2022. It aggregates records from 26 healthcare systems across 50 states with almost 80 million patients. We identified adults over 18 years old with colon cancer and obtained data on risk factors, including sex, age over 65 years, hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), atrial fibrillation, obesity, and tobacco use. Multivariable logistic regression was used to adjust for the variables collected. All tests were two-sided, and a p-value ≤ 0.05 was considered statistically significant. Results: A population of 69,339,860 was included. Colon cancer was diagnosed in 304,650 (0.4%) and CVA in 237,290 (0.3%). Males made 45%. The colon cancer group, compared to the background population, had a higher prevalence of patients aged over 65 years (66.8% vs. 30.7%), HTN (61% vs. 21.1%), HLD (50.7% vs. 16.9%), DM (31.4% vs. 8.8%), obesity (20.7% vs. 8.0%), tobacco use (12.5% vs. 6.6%) and CVA (5% vs. 0.3%). Multivariable logistic regression of variable studies (Table). Colon cancer was significantly associated with CVA. Conclusions: Our study included over 69 million adults, making it the most extensive population-based study of the risk of CVA in colon cancer in the United States. After adjustment for most established risk factors that may confound the result, colon cancer was associated with a significantly increased risk of CVA, and it was preceded only by HTN. Colon cancer portrayed more risk than atrial fibrillation. Limitations of population-based studies are several, including inaccuracies and miscoding. Our findings suggest that colon cancer survivors and patients with stable disease on treatment may have their prognosis and quality of life jeopardized by CVA. Prospective studies are needed, and management of modifiable risk factors in collaboration with primary care is paramount. [Table: see text]
The risk of myocardial infarction and heart failure in colon cancer in the United States: A population-based national study.
Authors: Brell Joanna M. , Elantably Dina , Al Armashi Abdul Rahman , Wang Jiasheng , Hammad Faris , Al Zubaidi Anas , Alkrekshi Akram 
Published: June 2023

e15517 Background: Colon cancer ranks third in cancer mortality and estimated new cases in the United States. Along with the improved treatment and increased participation in screening, there are more than 1.5 million survivors. Venous thromboembolism (VTE) is associated with cancers due to various mechanisms that are common with arterial thromboembolism. Still, there are limited population-based studies on the risk of myocardial infarction (MI) and heart failure (HF) in colon cancer. Methods: Retrospectively we analyzed data from a nationwide commercial database (Explorys, IBM) from 1999 to October 2022. It gathers records from 26 healthcare systems in 50 states with nearly 80 million patients. We identified adults over 18 years old with colon cancer, MI, and HF. In addition, we obtained data on risk factors, including sex, age over 65 years, hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), atrial fibrillation, obesity, and tobacco use. Multivariable logistic regression (MLR) was used to adjust for the variables collected. All tests were two-sided, and a p-value ≤ 0.05 was considered statistically significant—data presented as odds ratio (OR) with a 95% confidence interval (CI). Results: A population of 69,339,860 was included. Colon cancer was diagnosed in 304,650 (0.4%), MI in 1,691,900 (2.4%), and HF in 2,415,450 (3.5%). Males made 45%. The colon cancer group, compared to the background population, had a higher prevalence of patients aged over 65 years (66.8% vs. 30.7%), HTN (61% vs. 21.1%), HLD (50.7% vs. 16.9%), DM (31.4% vs. 8.8%), obesity (20.7% vs. 8.0%), and tobacco use (12.5% vs. 6.6%). MLR of variable studies (Table). Colon cancer was significantly associated with MI and HF. Conclusions: This is the largest population-based study of the risk of MI and HF in colon cancer in the United States. After adjustment for established risk factors that may confound the result, colon cancer was independently associated with a significant increase in the risk of MI and HF. Raising awareness among oncologists and cardio-oncologists' involvement at the time of diagnosis is essential to optimally and aggressively manage modifiable risk factors. Prospective studies are needed. [Table: see text]
Identification and evaluation of a reliable, non-invasive diagnostic method using serum microRNA expression to diagnose high-risk colorectal cancer candidates.
Authors: Foo Dominic Chi-Chung , Ng Lui , Law Wai-Lun 
Published: June 2023

e15519 Background: Screening is of paramount importance in early colorectal cancer detection which can significantly reduce its mortality. This study aims to identify a non-invasive diagnostic method using serum microRNA expression to diagnose colorectal cancer patients. Methods: Serum samples were prospectively collected from CRC patients or normal subjects during 2017 to 2021 in Queen Mary Hospital of Hong Kong and divided into 3 study cohorts: Training cohort (n = 129 per group), Validation cohort (n = 200 per group) and Prediction cohort (n = 260). Quantitative PCR was applied to detect the serum level of 20 candidate microRNAs. Multiple linear regression was used to formulate a serum microRNA panel for diagnosing CRC patients. The performance was evaluated by ROC analysis. The cost-effectiveness was investigating by comparing the cost of two CRC diagnostic strategies comprising of (i) colonoscopy alone and (ii) microRNA panel and followed by colonoscopy strategies to microRNA panel tested positive patients. Results: The values of 3 pairs of serum microRNAs, including miR-106b/miR-1246, miR-106b/miR-16 and miR-106b/miR-21 showed statistical significant difference between CRC patients and normal subjects. A serum microRNA panel formulated from these 3 pairs of microRNAs was able to diagnose CRC patients from normal subjects with high accuracy for both training cohort [AUC: 0.9078 (95% CI, 0.9122 To 0.9734; p < 0.0001)] and Validation cohort (AUC: 0.8904), suggesting that this microRNA panel had a consistent performance across different patient cohorts. Our prediction cohort showed that this microRNA panel was able to screen CRC patients with 85.8% sensitivity, 80.95% specificity, 86.9% positive predictive value and 79.4% negative predictive value. Cost-effectiveness analysis revealed that the strategy of combining serum miRNA test and colonoscopy was a more cost-effective approach compared to colonoscopy alone. The average cost saved per patient was around HK$4010. Conclusions: The serum miRNA test was a feasible, promising and cost-effective non-invasive biomarker for diagnosing CRC patients from normal subjects.
Genomic characterization of MSI-H and TMB in gastrointestinal cancer.
Authors: Zheng Zhi , Wang Zhouyang , Cheng Shaochen , Zhou Yujun , Liao Wenting , Zhen Baoling , Chen Yaru 
Published: June 2023

e15524 Background: Microsatellite instability (MSI) is a molecular marker of a deficient in mismatch repair (MMR) system. It is one of the main hallmarks in colorectal cancer (CRC) and gastric cancer (GC), occurring in 15% and 18% of CRC and GC respectively. Mutations occur in MMR system genes will impair DNA mismatch recognition and cause accumulation of mutations in DNA microsatellite regions. As a result, microsatellite instability-high (MSI-H) patients often possess an abnormally high number of somatic mutations and would lead to high tumour mutation burden (TMB), which is a prevalent biomarker in cancer immunotherapy. Here we analysed the genomic landscape of 974 gastrointestinal cancer patients to provide new insights on the relationship between MSI, TMB and other genetic mutation characteristics. Methods: Panel sequencing targeting 680 cancer-related genes were performed on patients with colonrectal cancer (n = 569), gastric cancer (n = 375), intestinal cancer (n = 25) and oesophagal cancer (n = 5) on either fresh tumour tissue or formalin-fixed paraffin embedded tumor DNA. Genomic alterations including single nucleotide variations, short insertions and deletions, copy number variations, tumour mutation burden and micro-satellite instability were analysed. Results: Among the 974 patients, 86 patients (8.83%) were classified as MSI-H based on evaluation of 117 MMR-related loci, while rest of the patients (n = 888, 91.2%) were classified as microsatelite stable (MSS). In MSI-H cohort, 68.6% of the patients were classified as TMB-H with a TMB level higher than 10 Muts/Mb, while in MSS cohort, only 3.71% of the patients were classified as TMB-H. The TMB value of MSI-H cohort is also significantly higher than the MSS cohort (p < 0.0001, two-tailed T-test). Meanwhile, we discovered that proportion of patients with mutated lysine methyltransferase family gene KMT2D (54.65% vs 7.17%, p < 0.0001), KMT2B (48.84% vs 3.25%, p < 0.0001) and KMT2C (44.19% vs 7.17%, p < 0.0001) showed significant difference between MSI-H and MSS cohorts (Two-sided Fisher’s exact test). Conclusions: This study demonstrated that MSI-H is highly correlated with TMB-H, providing a new insight of evaluating gastrointestinal cancer treatment on MSI-H patients. The study also revealed novel MSI-H genetic mutation landscape for KMT gene family. Concurrent with recent researches, this study further boosts the potential of KMT genes to be used as a biomarker in both diagnosis and immunotherapy treatment.
Oncologic outcomes in patients with radiation associated rectal adenocarcinoma.
Authors: Omer Dana Mohamed Rashid , Verheij Floris S , Luthra Anisha , Rosen Roni , Thompson Hannah M , Romesser Paul Bernard , Paty Philip , Garcia-Aguilar Julio , Sanchez-Vega Francisco 
Published: June 2023

e15529 Background: The rectal wall is often irradiated during pelvic radiotherapy for prostate cancer, potentially increasing the risk of rectal adenocarcinoma. The oncologic outcomes of rectal adenocarcinoma in previously irradiated patients remain largely unknown. Methods: We performed a retrospective analysis of patients with stage I-IV rectal adenocarcinoma after radiotherapy for prostate cancer (RCRPC). Clinical characteristics and treatment were compared to a background set of patients with rectal cancer not associated with prostate cancer (RCNAPC). We investigated the differences in survival using propensity score matching (1:1 ratio). Patients were matched based on stage, tumor size, distance from anal verge and circumferential tumor location, but were unable to be matched on age. Five-year disease-free survival (DFS), overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were visualized using Kaplan-Meier curves and statistical significance was assessed using log-rank tests. Results: The study included 66 RCRPC patients treated with prostate brachytherapy (n = 19), external beam radiation therapy (n = 31) or both (n = 16). The median latency period between the completion of prostate radiotherapy and the diagnosis of rectal cancer was 11.7 years. The median follow-up from rectal cancer diagnosis was 2.4 years. The median prostate radiation dose was 74 Gy. Compared to the 609 RCNAPC patients, the RCRPC group was older (median 78 vs 55 years, P < 0.001) and more likely to be stage I (24% vs 5%, P < 0.001). Tumors were more frequently found within the distal rectum (47% vs 22%, P < 0.001) and along the anterior rectal wall (33% vs 11%, P < 0.001). Patients in the RCRPC group were less likely to receive neoadjuvant chemotherapy (50% vs. 93%, P < 0.001), neoadjuvant radiation (21% vs 85%, P < 0.001), or undergo surgery (54% vs 61%, P < 0.001) compared to the RCNAPC group. The oncologic outcomes for the RCRPC group and matched cohort of patients with RCNAPC are presented in table 1. Conclusions: Patients with radiation associated rectal cancer have earlier stage tumors but show higher rates of distant metastasis and lower survival compared to nonirradiated patients. They are older and less likely to receive chemotherapy or radiation and are often poor candidates for radical surgery. Whether the worse outcomes are attributable to differences in patient characteristics, available treatment options or a more aggressive biology remains unknown. [Table: see text]
Colorectal cancer mortality in young adults in the United States.
Authors: Didier Alexander , Hamouda Danae M. , Sutton Jeffrey M. 
Published: June 2023

e15530 Background: Colorectal cancer (CRC) is typically considered a disease that affects older adults. However, recently a concerning increase in the incidence rates of CRC among young adults (age < 50) has been noted. Given the limited analysis of colorectal cancer mortality assessing for age-based differences, we aimed to characterize trends in mortality rates of CRC between 1999 and 2020 in the United States, with the hypothesis that younger patients would also experience an increasing morality rate from CRC in concert with the increasing incidence. Methods: We queried the Centers for Disease Control database for mortality statistics with an underlying cause of death of colon and rectal cancer between the years 1999 - 2020. Crude mortality rates (CMR) were calculated per 100,000 deaths. Patients were stratified based on early-onset (30-49 years), average-onset (50-69 years), and late-onset (70+ years) CRC. For each cohort, we examined race and U.S. Census Region variables to assess drivers in mortality. Temporal trends were assessed using Joinpoint regression software. Average annual percent change (AAPC) were considered statistically significant if p < 0.05. Results: Between 1999 and 2020, 1,166,158 deaths due to CRC occurred and the CMR decreased from 20.3 to 15.7. For patients aged > 70, colorectal cancer mortality rate decreased from 148.6 to 75.9 at an average of 3.2% annually during this time frame. For the group aged 50-69, there was a decrease in CMR from 32.7 to 24.2, reflecting an average annual decrease of1.4%. In patients aged 30-49, CMR increased from 3.6 to 4.2, reflecting an average annual percent increase in mortality of 0.7%. This increase in CRC mortality in the youngest cohort occurred independent of geographical location. Mortality in young adults increased the fastest in the West at a rate of 1.1% annually and slowest in the South at 0.4% annually. Similar increases in mortality rates were identified when cohorts were stratified by race, with Non-Hispanic American Indian/Native American populations experiencing the most rapid increases in mortality at 3.4% annually. Conclusions: These results demonstrate age-related disparities in recent CRC mortality trends. While the overall mortality of CRC has decreased over the last two decades, this decrease was largely due to declining mortality in older adults. In contrast, younger adults experienced a sharp rise in CRC mortality rates, increasing at an average annual percentage increase of almost 1% each year independent of racial or geographic factors. These results highlight a concerning emerging trend with significant public health implications and provide rationale for increased surveillance in young adults.