bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential expression of micro-RNA in tumor and non-tumor tissues of patients with colorectal cancer.
Authors: Novikova Inna A. , Timoshkina Natalya N. , Kit Oleg Ivanovich , Poluektov Sergey I. , Dashkov Andrey V. , Haragezov Dmitry , Tolmakh Roman E. , Kolesnikov Evgeniy N. , Dontsov Vladimir A. , Petrov Dmitry S. , Soldatkina Natalya V. , Gevorkyan Yuriy A. , Kutilin Denis S.
Published: May 2020

e13516

Background: The colorectal cancer (CRC) incidence is steadily increasing. Moreover, the problem of its early diagnosis remains unresolved due to the low specificity of known tumor markers, and the problem of creating new therapeutic approaches is due to the lack of a complete understanding of the mechanisms of regulation of gene expression in this oncopathology. The study of micro-RNAs (short non-coding RNAs that regulate gene expression) can be the solution to both problems. The aim of the study was to analyze micro-RNA differential expression in the tumor and non-tumor tissues of CRC patients. Methods: 5 patients with CRC (colon adenocarcinoma, G2) were selected for the multiple parallel micro-RNA sequencing. The mirVana miRNA Isolation Kit protocol was used to isolate small RNA fractions. The miRNA library was prepared using the TruSeq Small RNASample Preparation Kit. Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The copy numbers of micro-RNA were determined by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the differential expression of micro-RNA, the DESeq2 method implemented in R medium was used. Results: Six differentially expressed micro-RNAs were detected (p < 0.05): 2 that decrease expression (hsa-miR-143-3p,hsa-miR-26a-5p) and 4 increase expression in the tumor relative to non-tumor (hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p). The highest level of expression in both tumor and non-tumor tissue was observed for hsa-miR-143-3p, the lowest one for hsa-let-7i-5p. Moreover, the largest difference in micro-RNA expression in tumor tissue relative to non-tumor was shown for hsa-miR-92a-3p (4.5 times, p = 0.02), the smallest for hsa-miR-143-3p (2.4 times, p = 0.04). For miRNAs that differentially changed their expression, a search was made for target genes using the miRWalk 3.0 database. 14573 target genes were found, of which 3346 were for hypo-expressed micro-RNAs and 11228 for hyper-expressed micro-RNAs. Conclusions: Sequencing revealed 6 differentially expressed micro-RNAs (hsa-miR-143-3p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p) in the tumor tissue is relatively non-tumor tissues of the colon. The data obtained expand the understanding of the mechanisms of gene regulation in the context of this oncopathology and may possibly become the basis for highly specific tumor markers panel.
Druggable fusion gene landscape in solid tumors.
Authors: Williams Gareth Haydn , Thatcher Robert Paul , Nevado Polo Borja , Haddow Tiffany Eira , Hardisty Keeda-Marie , Loddo Marco
Published: May 2020

e13517

Background: Kinases activated by gene fusions represent an important class of oncogenes in solid tumors highlighted by the unique site agnostic FDA approval of larotrectinib for NTRK gene rearrangements. However, the frequency and types of druggable fusions in solid tumors are not well characterized from the clinical perspective. Methods: Oncofocus is a clinically validated precision oncology platform that includes analysis of 399 druggable driver-partner oncogenic fusion genes linked to 140 unique targeted therapy protocols. A retrospective analysis of Oncofocus trending data in a real-life cohort of 1111 patients has been used to determine the actionable fusion gene landscape in solid tumors. Results: Eighty nine actionable fusion genes were identified in 1111 samples of solid tumors linked to 73 targeted therapy protocols. Seven of the samples harbored multiple fusion genes. Eighty two of the 1111 samples tested had at least one actionable fusion gene representing a frequency of 7.38%. The highest frequency of actionable fusions were observed in glioblastoma (23%), head and neck (12%), kidney (11%) and prostate (10%) cancers. Four of the seven samples with multiple actionable fusions were found in glioblastoma. Pancreatic, lung and endometrial cancers and cancer of unknown primary (CUPs) had an actionable fusion gene frequency ranging from 7-9%. TBL1XR1-PIK3CA, MET-MET, WHSC1L1-FGFR1 and EGFR VIII fusions were identified as the most common druggable fusions. All actionable fusion genes were found to interact with one or more of the following pathways RAS/RAF/MEK/ERK, PI3K/AKT/MTOR, PLCy/PKC and JAK/STAT. Although a targeted agent for TRK fusions now has FDA approval, this rearrangement appears to be a rare event. In contrast, inhibitors targeting the TBL1XR1-PIK3CA, MET-MET, WHSC1L1-FGFR1 fusions and linked downstream signalling pathways appear to offer much broader clinical utility. Conclusions: Druggable fusions were identified at an unexpectedly high frequency and should therefore be included as part of routine comprehensive precision oncology testing. Notably, many of the actionable fusions are not tumor type specific reinforcing the “site agnostic” approach to profiling and supporting the concept of “molecular basket” clinical trials. Precision oncology trending data also provides actionable mutational landscapes which can be used to refine precision oncology testing, patient selection for targeted therapy protocols and enhancement of clinical trial design.
Genomic and epigenomic profiles to distinguish pulmonary enteric adenocarcinoma from lung metastatic colorectal cancer.
Authors: Wang Jie , Zuo Ying , Bai Hua , Duan Jianchun , Wang Zhijie , Li Weihua , Ying Jianming , Han Jie-Fei , Tian Yanhua , Chen Yedan , Shao Yang
Published: May 2020

e13528

Background: As an extremely rare variant of lung adenocarcinoma, the diagnosis of pulmonary enteric adenocarcinoma (PEAC) remains challenging in the clinic due to shared morphological and immunohistochemical features with lung metastatic colorectal cancer (mCRC). Current differentiation of PEAC and mCRC mainly relies on clinical history and pathological examination while which still remain risks of misdiagnosis. Due to their distinct treatment regimens, effective molecular markers are essential for accurate diagnosis. However, comprehensive molecular features of PEAC is still poorly understood. Methods: We performed whole-exome sequencing and targeted bisulfite sequencing of 23 PEAC and 20 mCRC and matched normal tissue to improve molecular characterization. For DNA methylation profiling, differentially methylated regions (DMR) were analyzed by comparing PEAC with normal lung tissue and with mCRC. We also trained machine learning methods to distinguish PEAC from mCRC and validated the classifier in an independent cohort with 10 PEAC and 10 mCRC. Results: Mutations of KRAS, APC, and EGFR, alterations of chromosome arms 13q, 14q and 18p were found to be the major differential genetic alterations between PEAC and mCRC (P < 0.05), yet not enough to aid clinical diagnosis. For epigenomic profile, we identified 524 DMRs (false discovery rate ≤0.05) which were further reduced to 30 DMRs according to importance rank by the random forest algorithm. Based on these DMR features, we developed a diagnostic classifier that correctly classified 95.1% of patients in this discovery cohort. We further validated this predictive model in the validation cohort, with a prediction accuracy of 90.0%. We demonstrated its clinical application in two cases with difficulties to diagnosis by traditional methods. Conclusions: We have illustrated the unique genetic and methylation profiles of PEAC and mCRC. Our approach for disease classification may have a substantial impact on diagnostic precision and therapeutic decision for PEAC.
The effect of transcriptional activity of genes regulating DNA repair and apoptosis on the effectiveness of radiation therapy in rectal cancer patients.
Authors: Kosheleva Natalia G , Gusareva Marina A. , Udalenkova Irina A. , Rozenko Lyudmila Y. , Donskaya Aliya K. , Fatkina Natalya B. , Gabrichidze Peter N. , Solntseva Anna A. , Karnaukhova Elena A. , Krokhmal Julia N. , Vasilyeva Ekaterina O. , Kit Oleg Ivanovich , Kutilin Denis S.
Published: May 2020

e13531

Background: Preoperative radiation therapy (RT) followed by surgery is the main effective treatment for colorectal cancer. However, some patients do not respond to preoperative RT due to the radioresistance of tumor cells, depending on their molecular characteristics, in particular on the expression of a certain group of genes. The aim of this work was to study the effect of expression of BRCA2, H2AX, RBBP8, CASP9 and BCL2 genes on the effectiveness of preoperative RT for rectal tumors. Methods: In the study, paired biopsy preparations (obtained by VCS before irradiation) of normal and tumor tissues of the rectum (adenocarcinoma G1-2) in 30 patients were used. RT was carried out on a Novalis TX linear accelerator (Varian, USA) (SFD = 2.4 Gy to TFD = 54 Gy). RNA isolation was performed by Chomczynski&Sacchi method. Reverta-L kits were used to synthesize cDNA libraries. Using the RT-qPCR method, the relative expression of 5 genes was determined: BRCA2, H2AX, CASP9, RBBP8 and BCL2 (reference GAPDH, ACTB and B2M). Statistical analysis was performed using the Shapiro–Wilk and Mann–Whitney criteria. Results: 2 clusters of patients were identified that differed in the expression of the BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes. In cluster 1, 81% of patients had increased expression of the CASP9 gene and 100% decreased expression of the BRCA2, H2AX, RBBP8, and BCL2 genes. In cluster 2, the expression of the CASP9 gene was reduced in 100% of patients and the expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was increased in 93%. A subsequent analysis of the results of RT showed that 16 patients had complete tumor regression after RT, while expression of the H2AX and RBBP8 genes was reduced by a factor of 2 (p < 0.05), and the expression of the CASP9 gene was increased by a factor of 4 (p < 0.005) relative to normal tissues. 8 patients showed slight tumor regression, and 6 patients had no regression at all, while their expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was statistically significantly (p < 0.005) 2, 4, 6 and 3 times higher, respectively, and that of CASP9 gene was 4 times lower than in patients with complete tumor regression. Conclusions: The study found that the expression of BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes affects the effectiveness of RT, enhancing it in patients with increased expression of CASP9 and reduced expression of H2AX and RBBP8, and vice versa, the effectiveness of therapy decreases with increased expression of H2AX, RBBP8, BRCA2 and BCL2.
Characteristics of breast cancer in Slovenian patients with germline CHEK2 c.444+1G>A mutation.
Authors: Besic Nikola , Blatnik Ana , Nizic-Kos Tea , Novakovic Srdjan , Krajc Mateja
Published: May 2020

e13536

Background: Different CHEK2 germline pathogenic variants/likely pathogenic variants (PV/LPV) are associated with distinct immunophenotypic molecular subtypes of breast cancer (BC). The aim of our study was to explore the characteristics of Slovenian BC patients with CHEK2 c.444+1G > A variant. Methods: Germline CHEK2 pathogenic PV/LPV were identified in 76 individuals from 50 families who underwent genetic counseling and testing using a multigene panel at our institution from year 2014 to 2019. The data on 41 Slovenian BC patients with CHEK2 PV/LPV were retrospectively collected and analyzed, with an emphasis on c.444+1G > A variant carriers. Results: BC in our CHEK2 positive patients was diagnosed in 40 females and one male. Mean age at BC diagnosis was 42.8 years (range 21-63). Four recurrent CHEK2 PV/LPV were found in 80% (33/41) of our BC patients: c.444+1G > A (12/41; 29%; 11 females, one male), c.349A > G (9/41; 22%). deletion of exons 9-10 (7/41; 17%) and c.1100delC (5/41; 12%). There was a trend for c.444+1G > A carriers to develop BC at younger age in comparison to patients with other CHEK2 PV/LPV (mean age 39.3 vs. 44.2 years; p = 0.089). None of the patients with the c.444+1G > A variant had invasive lobular carcinoma. Median tumor size in patients with c.444+1G > A variant was 34 mm and median number of positive lymph nodes was 2.67 (range 1-8). Patients with c.444+1G > A variant had a luminal A subtype in 2 cases, luminal B in 7 cases, HER2+ subtype in 3 cases, while none of patients had a triple negative BC. Mastectomy, tumorectomy and axillary lymphadenectomy was performed in 8, 4 and 12 patients, respectively. All c.444+1G > A carriers had to be treated with chemotherapy and external beam irradiation. Patients with the c.444+1G > A variant were more often treated with chemotherapy (p = 0.038) and/or external beam irradiation (p = 0.014) in comparison to patients with other PV/LPV. Distant metastases were diagnosed in two patients at age 45 and 47. Conclusions: Mutation c.444+1G > A was detected in 29% of Slovenian patients with CHEK2 PV/LPV. Distant dissemination was diagnosed despite aggressive treatment at a young age in 16% of these patients.
Exploring African American males' attitudes towards genetic testing for prostate cancer risk.
Authors: Leader Amy , Fortune Thierry , Weddington Pamela , Crumpler Nicole , Giri Veda N.
Published: May 2020

e13552

Background: African American (AA) males have disproportionately high prostate cancer (PCA) incidence and mortality rates compared to men of other races. While genetic testing for PCA is rapidly expanding, AA men represent fewer than 10% of those who undergo genetic counseling and testing. Barriers for AA males may include a lack of awareness or understanding, cultural beliefs, financial and access-to-care limitations, fear of discrimination, and mistrust in the healthcare system. These issues may be exacerbated among low-income, urban AA males. Methods: We conducted two focus groups with AA males who live in a low-resource neighborhood in a major US city to explore their understanding about PCA, challenges in obtaining and discussing family health history, and attitudes towards genetic counseling and testing. Prior to the start of the focus groups, men provided informed consent and completed a brief survey to capture demographic and health history information. Focus groups were moderated by a male member of the community, were audio and video recorded, and transcribed verbatim. Transcripts were analyzed using NVivo 12 to deduce themes within the discussions. Results: Seventeen men participated in one of two focus groups. The mean age was 54 years old (range: 40-66). Only 5 men (30%) were married. Ten men (60%) did not report a family history of PCA, while the remaining 7 reported that their father, grandfather, brother or uncle had PCA. All men had a primary care visit in the past 3 years, but only 13 out of 17 men (76%) reported discussing PCA. Focus group discussions and analyses revealed multiple key themes. Men had limited understanding of the prostate and PCA, with somewhat fatalistic views toward cancer. Family history was recognized as an important risk factor for cancer; talking about family history has become easier and more widely accepted. However, there was mixed reaction to genetic testing: most men were unfamiliar with it but were in favor of learning more, while a few did not see the utility of genetic information. Conclusions: AA men continue to have knowledge deficits about PCA. While there is strong understanding that cancer may be hereditary, there is less awareness about PCA genetic testing. Targeted genetic education and addressing access and cost barriers to genetic testing among AA males is needed to increase uptake of genetic testing and participation in genetic trials.
Treating obesity as primary prevention of cancer.
Authors: Ferdous Chowdhury , Islam Tareq
Published: May 2020

e13556

Background: Prevalence of obesity in Hispanic population has been increasing. Obesity is a ‘super carcinogen’ and largely modifiable factor. We hypothesize due to current increase in prevalence of obesity there will be similar change in trend of malignancy among Hispanics and treating obesity can lead to decrease prevalence of both health conditions. Methods: National Health and Nutrition Examination Survey (NHANES) from year 1999 through 2016 was used to analyze obesity prevalence across different races. Surveillance Epidemiology and End Result (SEER) data was analyzed for racial distribution of overall and different kind of malignancies stratified by different races from 1999 through 2016. Differences of prevalence among different groups were calculated using likelihood ratio. Results: After exclusion criteria final sample size was 48,816 from NHANES and 6,868,226 from SEER dataset. Prevalence of obesity steadily increased in all races with highest change in Hispanics (31.7% in 1999-2000 to 47.3% in 2015-2016). Proportion of Hispanics with cancer also steadily increased from 7.5% in 1999-2000 to 11.3 in 2015-2016 in SEER dataset. States with high Hispanic population (New Mexico, California and New Jersey) had higher proportion of breast cancer (15.4%) compared to other states (14.5%) (p-value < 0.0001). Conclusions: Upward trend of obesity and malignancy is evident among Hispanic population. Hispanic populated states are showing higher prevalence of certain metabolically active malignancies. This increase in prevalence can be explained by “Migration Effect”. By intervening obesity 18% population attributable factor (PAF) is achievable. Opportunity exists to change this increasing trend in cancer epidemiology by treating obesity as primary prevention.
Dietary consumption of tea and the risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.
Authors: Thomas Robert J. , McConnachie Alex , Stanley Bethany , Williams Madeleine
Published: May 2020

e13559

Background: The popular beverage tea, brewed from infused leaves of camellia sinesis, contains non-phytoestrogenic polyphenols such as flavonoids, anthocyanidins, flavanols (epigallocatechin gallate); phenolic acids (ellagic acid) and stimulants (caffeine, theophylline). Laboratory studies report tea promotes antioxidant enzyme formation, slows cancer cell proliferation and unblocks apoptosis. Clinically, the Pomi-T randomised study reported tea extract (along with three other foods) reduced PSA progression in men with prostate cancer1. Evidence of prostate cancer prevention, however, from prospective cohort data is conflicting with one recent study even implying an increased risk2. Methods: We analysed 25,097 men within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of prostate cancer were reported in 3,088 men (12.3%) during the 11.5 year follow up. Tea consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between tea intake and prostate cancer incidence. Results: Overall tea consumption was associated with a significantly lower risk of prostate cancer (p = 0.009). More precisely, the participants in the highest third of consumption group had a significantly lower risk compared to those in the lowest third (HR 1.16 (CI 1.05-1.29, p = 0.004). This pattern persisted with adjustments for age, sex, race and education level (p = 0.034), family history of cancer (p = 0.037). Those who never drank tea, however, had no statistical lower risk of prostate cancer compared to other groups (p = 0.501). Conclusions: Among tea drinkers, this data revealed a positive association between drinking tea and a reduced risk of prostate cancer. This data supports the consideration of future prospective intervention studies investigating the role of tea as part of a prostate cancer prevention programme. 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer & prostatic diseases (2014), 2,180. 2. Reger et al. Dietary isoflavones and prostate cancer risk. Int J. Cancer (2017), 142; 4, 719.
Dietary intake of broccoli and the risk of cancer in the prostate, lung, colorectal, and ovarian cancer (PCLO) screening trial.
Authors: Thomas Robert J. , McConnachie Alex , Williams Madeleine M A , Stanley Bethany
Published: May 2020

e13560

Background: The cruciferous vegetable broccoli, are a good source of vitamins, minerals and fibre, as well as thiol phytochemicals (indole-3-carbinol), glucosinolates (isothiocyanates, its metabolite, sulforaphane), carotenoids (lutein and zeaxanthin) and flavonols (kaempferol). Laboratory and human biopsy studies have found that broccoli intake influenced epigenetic expression of genes via blockage of histone deacetylase which reduce inflammation and cancer growth. Clinically, a randomised control study reported dried broccoli extract (along with three other foods) influenced PSA progression in men with prostate cancer1. However, no preventative intervention studies in humans have been conducted and data from cohort studies are inconsistent for its influence on cancer incidence2,3. Methods: We analysed 49,104 people within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of any cancer were reported in 8,263 (16.83%) during the 11.5 year follow up. Broccoli consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between broccoli consumption groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between broccoli intake and cancer incidence. Results: Broccoli consumption was associated with reduced cancer incidence: HR 0.95 (CI 0.93-0.97, p < 0.001). This pattern persisted with adjustments for age, sex, race, education level and family history (HR 0.97, CI 0.96-0.99, p = 0.007) as well as smoking, BMI and alcohol consumption (HR 0.98, CI 0.96-0.99, p = 0.010). Conclusions: The study identified an association between increased broccoli consumption and reduced cancer risk. In practical terms, 15g of broccoli, or more, consumed per day (about a small cup) was associated with a 5% lower risk of cancer. Broccoli should continue to be included in healthy eating advice. This data supports the consideration of future prospective intervention studies investigating the role of broccoli as part of a cancer prevention programme. References 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer & prostatic diseases (2014), 2,180. 2. Liu et al Cruciferous vegetables inversely linked with breast cancer: Breast (2013), 22;3,309. 3. Bosetti et al Cruciferous vegetables and cancer risk Ann Oncol (2012) 23(8);2198.
Association of chronic hepatitis C virus infection with an increased risk of lung cancer: A systematic review and meta-analysis.
Authors: Ponvilawan Ben , Charoenngam Nipith , Rujirachun Pongprueth , Wattanachayakul Phuuwadith , Tornsatitkul Surapa , Rittiphairoj Thanitsara , Ungprasert Patompong
Published: May 2020

e13562

Background: Chronic hepatitis C virus (HCV) infection is associated with increased risk of multiple types of extrahepatic cancer, such as lymphomas, thyroid cancer and renal cancer. However, whether HCV infection also increases the risk of lung cancer is still inconclusive. This systematic review and meta-analysis was performed in order to determine the relationship between chronic HCV infection and lung cancer. Methods: A systematic review was performed using EMBASE and MEDLINE databases from inception to November 2019 with search strategy that represents “hepatitis C virus” and “cancer”. Eligible studies must be cohort studies which include patients with chronic HCV infection and comparators without HCV infection, then follow them for incident lung cancer. Relative risk, incidence rate ratio (IRR), standardized incidence ratio, or hazard risk ratio of this association along with associated 95% confidence interval (CI) from each study were extracted and combined for the calculation of the pooled effect estimate using the random effect, generic inverse variance. Results: 20,459 articles were discovered using the aforementioned search strategy. After two rounds of review, eight studies fulfilled the inclusion criteria and were included into the meta-analysis. Chronic HCV infection was significantly associated with increased risk of lung cancer with the pooled relative risk of 1.94 (95% CI, 1.56 – 2.42; I2 = 87%). Funnel plot was fairly symmetric and not suggestive of presence of publication bias. Conclusions: Chronic HCV infection is significantly associated with a 1.94-fold increased risk in the development of lung cancer compared to no infection.
The role of HPV vaccination as a cancer prevention agent.
Authors: Mullai N , Osman Soleiman , Rattenni Joseph
Published: May 2020

e13566

Background: Human papilloma virus (HPV) is the most common sexually transmitted agent and has extensive association with many malignancies such as cervical, vaginal, vulvar, penile, and head and neck cancers. Vaccination helps prevent sexually transmitted diseases due to HPV. In addition, it provides protection against cancers caused by persistent, high-risk HPV infection in both male and female. Methods: Data collected from the medical records of patients diagnosed with anogenital, and head and neck cancers during 2017-2019 were studied retrospectively and the association of HPV infection was analyzed. Results: There were thirty-three cases of anogenital, and head and neck cancers diagnosed during the study period. The following were the occurrences: penile cancer 1, anal cancer 4, cervical/uterine/vaginal cancers 10, and head and neck cancer including tonsil, base of tongue, vocal cord, and glottis 18. HPV status was available in twenty-six (79%) patients. Fourteen patients were positive for high-risk 16/18 HPV strain, twelve were HPV negative, and HPV status was unknown for seven patients. Most of the patients were smokers and none of them had received HPV vaccination. The patients were treated appropriately with chemotherapy, radiation, and surgery. Conclusions: Human papilloma virus (HPV) infection type 16/18 is the most common sexually transmitted infection associated with significant anogenital and head and neck cancers.Vaccinations protect against persistent, high-risk HPV infection that may lead to malignancies. However, the HPV vaccination initiation and completion rates are only 41.7% and 21.6% respectively in males, and 60% and 39.7% respectively in females. The lack of opportunity does not appear to be a major reason for this low coverage. Some of the barriers for low adoption of HPV vaccination were concern about vaccine safety (70%), lack of knowledge about HPV related diseases (56%), very young to vaccinate (56%), fear of riskier sexual behavior (56%), and reluctance as not being included in the required immunization schedule (71%). In addition, several people refused HPV vaccination due to misinformation in social media. The primary purpose of HPV vaccination is to help prevent sexually transmitted diseases. Further, such vaccination can also prevent several cancers caused by persistent infection. Therefore, HPV vaccination has the potential to eliminate such risk if enforced at a young age in school. The above study and data stress this role and the importance of public awareness of the HPV vaccine as a cancer prevention agent.
Lung cancer incidence in never smokers in the Southeast of Brazil: 10 years analysis.
Authors: Pulido Jose Zago , Aleixo Sabina B. , Parmanhane Narelle
Published: May 2020

e13571

Background: Lung cancer is a leading cause of cancer death worldwide. In Brazil, the Ministry of Health estimated an absolute incidence of 30,200 cases of lung cancer in 2020. Eighty-five percent of diagnosed cases are associated with consumption of tobacco products. Although smoking remains the predominant cause, lung cancer in never smokers is an increasingly prominent public health problem. However, data on this topic, particularly lung cancer incidence rates in developing countries in never smokers are limited. Methods: The data presented in this work correspond to the period from 2007 to 2017 and were extracted from the database of the Hospital Cancer Registry of the Evangelical Hospital of Cachoeiro de Itapemirim (RHC / HECI) through SisRHC, a computerized database management tool for Hospital Cancer Records. Results: Of the 494 patients who were diagnosed with lung cancer aged 18 years or over, 395 (80%) had complete information on a history of tobacco use, of which 68 patients denied smoking. Based on data from 68 patients, the years 2011 and 2012 had the lowest incidence, 6%, of non-smokers with lung cancer. 2009 and 2007 were the years with the highest incidence, 24 and 33% respectively. In the remaining years, the percentage varied between 15 and 23%. Regarding gender, 47 (69%) of the cases were women and 21 (31%) were men. Adenocarcinoma without a specific origin (NOS) was the most frequent histological type in non-smoking patients, with 33 (48.5%) of the cases, followed by malignant neoplasia 10 (14.7%), squamous cell carcinoma NOS 8 (11, 8%) and NOS carcinoma 7 (10.3%), the types of NOS large cell carcinoma, NOS small cell carcinoma, NOS papillary carcinoma, NOS bronchioloalveolar adenocarcinoma and adenosquamous carcinoma account for 10 (14.7%) cases. Analyzing the clinical staging (CE) at the time of diagnosis, 1 (1.5%) had EC 1, 4 (5.9%) EC 2, 12 (17.6%) EC 3, 42 (61.8%) EC 4 and 9 (13.2%) had no reports of staging. The median incidence rate was 17%, confirming that smoking remains the biggest cause of lung cancer, and reinforcing the need for more comprehensive epidemiological analyzes for this population. As the data can reach even higher percentages, as the information is provided by patients, without an available reliability assessment method. Conclusions: Lung cancer in never smokers is a major public health problem and further exploration of its patterns of incidence, etiology and biology is needed.
Highlights of BRCA genetic testing in prostate cancer from a real-world patient cohort in Australia.
Authors: Tinton Inga , Spence Lara , Henry David H.
Published: May 2020

e13574

Background: There is an increase in interest and awareness in BRCA 1/2 testing recently. However, despite high awareness of these tests due to their frequent use among patients with certain cancer types such as ovarian cancer or breast cancer, BRCA testing is still only emerging in the prostate cancer (PC) treatment landscape. This study aims to understand what is driving the interest and use of BRCA testing in PC as well as the main barriers to testing in Australia. Methods: Between September 2019 and November 2019, n = 51 physicians of different specialties (n = 26 medical oncologists, n = 11 urologists, n = 14 pathologists) in Australia provided their quantitative and qualitative insights on BRCA testing. Medical oncologists and urologists (n = 37) also submitted patient tissue record forms of PC patients (n = 102) who received at least one biomarker test. The findings are derived from perceptual questionnaires, patient tissue record forms, and qualitative interviews. Results: The data suggests high (100%) awareness of BRCA testing in PC among medical oncologists and urologists, however that’s not the case among pathologists (36%). BRCA testing was seen in almost half of the patient records collected, primarily as blood tests (40%) as opposed to tissue (28%) or any other tests. Larger number (40%) of blood tests are carried out post-diagnosis with almost half (46%) of them initiated due to family history. Prior treatment history and patient request are more common patient selection criteria when deciding whether to test any PC patient for BRCA. The main barrier (64%) to BRCA testing is lack of funding/reimbursement for the test in PC at the moment. Only clinical trial PC patients typically have access to funded BRCA tests or those patients who are supported by the genetic counsellor program. Conclusions: Driven by significant uptake in ovarian and breast cancer and high awareness among oncologists and urologists, BRCA testing for prostate cancer is being increasingly used in the clinical setting in Australia. However, significant barriers remain; addressing these barriers should result in further uptake.
Molecular testing patterns and implications for treatment at a cancer center.
Authors: Lam Clarissa , Mallen Adrianne Rose , Walko Christine Marie , Chern Jing-Yi
Published: May 2020

e13576

Background: Genetic testing has revolutionized the care of ovarian cancer, providing a potential for targeted therapies and cancer prevention through cascade testing. Previous historical control for genetic testing rate of 28.5% at our institution, this initiated a multilevel intervention to improve guideline concordant care. The main objective of this study is a descriptive analysis of genetic testing patterns with the implementation of a genetics tumor board (GTB) at an NCI comprehensive cancer center (CCC). Methods: All gynecologic oncology cancer patients who underwent somatic testing from 3/2019 to 1/2020 were included in gynecologic oncology GTB. A descriptive analysis was performed on the ovarian cancer patients. Information regarding patient demographics, cancer characteristics, treatment, and follow-up were obtained from the medical records. Results: There were a total of 81 patients included in GTB during this time period. Fifty-four of 81 (66.7%) received care at our CCC and 27 of 81 (33.3%) were seen as a second opinion case. The patients included in GTB were comprised of recurrent ovarian cancer cases and newly diagnosed ovarian cancer cases. Of the patients included in genetics tumor board, 58 of 81 (71.6%) of patients received both germline and somatic testing. Genetics referrals were placed for 16 of 23 (69%) of the patients who received somatic testing without subsequent germline testing. Twelve of 81 (14.8%) GTB patients were identified for clinical trials during this time period. Conclusions: Genetic testing has become a cornerstone to ovarian cancer care. Implementation of a genetics tumor board at our institution has increased rates of germline testing compared to historical controls. With genetic tumor board being made up of a third of patients seeking a second opinion, we are able to provide comprehensive care to such patients in the form of genetic counseling referrals and clinical trial opportunities. Genetics tumor board also appears to highlight the cohort of patients with the most aggressive cancers: high-grade, advanced stage, and high rates of recurrence. This can potentially improve care by providing an arena for a multidisciplinary discussion of our most complex patients. Ongoing studies with the implementation of our cancer pathways may help determine which modifiable factors can be targeted to help increase adherence to genetic testing recommendations as we continue to strive for guideline-based care.
Cancer incidence in Behçet's Disease.
Authors: Guven Deniz Can , Bolek Ertugrul Cagri , Altintop Sabri Engin , Celikten Burcu , Aktas Burak Yasin , Kiraz Sedat , Gullu Ibrahim Halil , Karadag Omer , Dizdar Omer
Published: May 2020

e13583

Background: Previous studies demonstrated increased risk of cancer in systemic autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE) and sjögren syndrome due to uncontrolled inflammation. Behçet’s disease (BD) was also reported to be associated with an increased risk of cancer, although data is limited and differences in study designs was an important issue. In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the Turkish National Cancer Registry (TNCR) in the same age and gender groups. Methods: The study cohort consisted of BD patients of > 18 years old age and without a prior cancer diagnosis who were prospectively recorded in Hacettepe University Vasculitis Center. Data on any cancer was collected from the patient files. Cancer incidence was compared with age- and gender-specific cancer incidence rates of the normal population retrieved from the 2014 Turkish National Cancer Registry (TNCR) data using standardized incidence rates (SIR). Results: Totally 451 adult cases with BD were included in the study. The median age of the cohort was 43 (20-75) and 52.5% of the patients were males. Eleven cancer cases were observed during a median 124 months follow up. Behçet’s Disease was associated with an increase in cancer risk compared to expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p < 0.001). Cancer risk was particularly increased in men (SIR: 5.63, 95% CI: 2.62–10.70, p < 0.001) compared to TNCR data. Patients with papulopustular lesions had a trend towards a decreased risk of cancer (p = 0.060) and patients using azathioprine had a significantly decreased cancer risk (p = 0.031). Conclusions: This study revealed the cancer risk of patients BD was increased approximately three times compared to corresponding age and sex group. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.
A retrospective chart review evaluating the relationship between cancer diagnosis and drinking water source on the Lower Eastern Shore of Maryland.
Authors: DeRidder Angela Marie , Kalluri Sowjanya , Holdai Veera
Published: May 2020

e13587

Background: The lower Eastern Shore of Maryland is an agricultural and rural region with high cancer rates. The purpose of this retrospective study was to determine if cancer patients on the lower Eastern Shore utilize higher rates of well water compared to individuals in the general county population. Methods: A retrospective chart review of all cases of colon, lung, melanoma and breast cancer diagnosed at Peninsula Regional Medical Center in 2017 was completed. Demographic and clinical information including family, smoking and prior cancer history, as well as residential water source were recorded. Individuals with residential addresses outside of Wicomico, Worcester and Somerset counties were excluded. Overall well water use for each county was determined using U.S. 2010 census data. Fisher’s exact test was used to compare well water utilization rates in cancer patients and the overall county population. Results: 631 patient cases were reviewed and 384 patients were identified for data analysis. The majority of patients were white (81%), diagnosed with breast cancer (41%), and used well water (52%, n = 209). Cancer patients in the three counties combined were significantly more likely to use well water than individuals in the general county population (OR = 2.5, 95% CI 2.11, 3.16). In Wicomico county, 61% of cancer patients used well water (n = 140). Wicomico cancer patients were more likely to use well water than individuals in the general Wicomico county population (OR = 4.4, 95% CI 3.41, 5.78). No significant findings were observed for patients living in Worcester and Somerset counties. No differences in family, smoking or prior cancer history in patients using well water versus municipal water were identified. Conclusions: Cancer patients on the lower Eastern Shore of Maryland used well water more than municipal water. Cancer patients also utilized higher rates of well water compared to individuals in the general county population. Interpretation is limited by small sample size and lack of causality, however the results signal a need for additional studies evaluating well water use and cancer risk in this region.
Association of tumor mutational burden with age in solid tumors.
Authors: Yu Zhuang , Wang Jing , Feng Lingxin , Yang Xue , Qi Qi , Li Wenqi , Zhang Xing , Ge Minhui , Qin Huijuan
Published: May 2020

e13590

Background: Immunotherapy is becoming one of the promising treatments for cancer administration, and several studies indicated a better outcome was received in patients with high tumor mutation burden (TMB). The distribution of TMB is still unknown and this study aimed to analysis the association between TMB and age especially in East Asian populations. Methods: In our study, TMB value was measured as the numbers of synonymous, nonsynonymous mutations and InDels by next generation sequencing with 539 genes panel in tumor tissue. TMB-H was defined as highest mutation load quintile (top 20%) in each cancer type. The association between TMB and age in 874 patients was investigated including 174 patients with liver cancer, 32 patients with bile duct cancer, 54 patients with gastric cancer, 119 patients with colorectal cancer, 27 patients with pancreatic cancer, 32 patients with melanoma, 25 patients with glioma and 411 patients with lung cancer cases, respectively. Spearman rank correlation analysis, Mann-Whitney U-test and Fisher’s exact test were used for statistical analysis. Results: A significant correlation between TMB and ages was observed in patients with solid tumors (r = 0.204, p = 1.263×10−9). The median age of included patients was 60 years-old. Based on nonparametric test, the value of TMB in patients with liver cancer ( p = 2.310×10−4), gastric cancer ( p = 0.029) and lung cancer ( p = 0.001) aged ≥ 60 years-old was significantly higher than the corresponding patients aged < 60 years-old. No significant differences of TMB values were found between patients < 60 and ≥ 60 years-old in bile duct cancer ( p = 0.419), colorectal cancer ( p = 0.075), pancreatic cancer ( p = 1), melanoma ( p = 0.952) and glioma ( p = 0.720). The TMB-H ratio in patients with liver ( p = 0.049) and gastric ( p = 0.015) cancer aged < 60 years old was significantly lower than patients aged ≥ 60 years-old. Conclusions: Our study indicated the TMB value and TMB-H ratio were relatively higher with ages ≥ 60 years old in specific tumors, which might provide useful information to guide precisely the the application of PD-1 or PD-L1 inhibitors. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Impact of socioeconomic status on the incidence and mortality of multiple myeloma in the United States.
Authors: Omore Ibrahim , Sheppard Richard Stephen , Beale Stefani
Published: May 2020

e13595

Background: Socioeconomic deprivation is known to be associated with poorer survival among cancer patients, but studies has not shown the impacts of socioeconomic status on the Incidence and mortality of multiple myeloma. This article analyzed the socioeconomic inequalities in United States Multiple Myeloma Incidence and Mortality. Methods: We examined national trends in the Incidence and Survival disparities among patients with Multiple Myeloma by race/ethnicity and socioeconomic status. A retrospective cohort of Multiple Myeloma patients diagnosed from 2012 to 2016 belonging to all age groups, genders, income per household and level of education was identified from Surveillance, Epidemiology and End results database, United States Cancer Statistics and Population data from Census Bureau. Results: We found mortality to be higher among African American and in States with low median household income and low level of education. In conclusion our study shows a strong correlation between social deprivation and decreased survival in patients with Multiple Myeloma in all age groups. Also we found that Asians and Pacific Islanders seems to have higher survival compare to African Americans and Other ethnicities. Conclusions: Census‐based socioeconomic measures such as poverty and education levels could serve as important surveillance tools for monitoring trends in cancer‐related health inequalities and targeting interventions.
Former smokers as the most frequent smoking status in patients with lung cancer in Brazil.
Authors: Costa Guilherme Jorge , Mello Maria Julia Gonçalves , Ferreira Carlos Gil , Bergmann Anke , Thuler Luiz Claudio Santos
Published: May 2020

e13597

Background: Lung cancer is the principal cause of death from cancer worldwide. However, little is known of the clinic and histological profile from former smokers patients with lung cancer. Objectives: To characterize the clinical and histological profile and to identify independent factors associated with smoking status (former versus current) in patients with lung cancer in Brazil between 2010 and 2016. Methods: An ecological study was conducted using data from Brazilian hospital-based cancer registries between 2010 and 2016. Data with p-value < 0.20 in the univariate analysis were included in the logistic regression analysis by using the stepwise forward method, in order to control for potential confounders. Results: This study evaluated 23,462 patients with lung cancer diagnosed between 2010 and 2016 in Brazil. In general, the average age of all patients was 63.7 + 10.7 years old. Never smokers, former smokers and current smokers corresponded to 18.9 %, 35.2% and 45.9% of cases in the moment of the diagnosis, respectively. Current smokers were the most frequent smoking status, albeit its frequency decreased significantly during the period. Male and female former smokers had its frequency increasing over the period and male former smokers became more frequent than males current smokers since 2015. In multivariate analysis, comparing former versus smokers, the follow variables were statistically significant: former drinkers, older age group, higher schooling, married or living married, from non-public (private) health system insurance, living in region North, Northeast and West Center and more recent year of diagnosis. Conclusions: Recently, former smokers with lung cancer is increasing and became the most frequent smoking status, as a result of the very effective policies against to smoking in Brazil since 1990’s. The increase in that specific population discloses some interesting challenges and opportunities in clinical and translational settings.