Familial Cancer Research Articles

Assessing Hereditary Cancer Awareness among Medical Faculty Students: Development and Psychometric Evaluation of the Hereditary Cancer Awareness Scale

Purpose: Cancer is the first or second leading cause of death in Worldwide. About 5 percent to 10 percent of most all cancers are caused by inherited mutations. This rate is up to 50 per cent in some cancers. Medical faculty graduates are the first group in contact with patients compared to specialized physicians. The level of knowledge or awareness of this group about familial inherited cancers is important in terms of early detection of cancer in the community. The main purpose of the study was to develop a cancer awareness scale in medical students and to test its validity, reliability and item analysis Methods: This scale was developed by three methods. Firstly Exploratory Factor Analysis, secondly Confirmatory Factor Analysis and finally Reliability and Item Analysis. Results: The Hereditary Cancer Awareness Scale (HCAS) is a reliable and valid measurement tool to assess the awareness of Hereditary cancer among medical students. Conclusions: The use of this scale in medical education and in the design of cancer awareness programs is important in terms of increasing awareness of cancer and preventing familial hereditary cancer in the future

Longitudinal Analysis of Cancer Family Caregiver Perception of Sleep Difficulty During Home Hospice.

Sleep difficulty in caregivers is associated with poor physical and psychological outcomes. The purpose of this study was to describe family caregivers' perception of sleep difficulty through the hospice trajectory after a cancer diagnosis as predicted by age, sex, self-report of anxiety or depression, and cohabitation. We conducted a secondary analysis of longitudinal data using multilevel modeling with nested model comparisons. Beginning with an unconditional growth model, predictors were added to nested models to test differential impact. Caregivers (n = 164) were predominately white (n = 160; 97%) and female (n = 113, 69%). We hypothesized that age, sex, history of anxiety or depression, and cohabitation would predict sleep difficulty. The cohabitation predictor model was a statistically significant model for caregiver perception of sleep difficulty that worsened throughout hospice caregiving (b = .184, 2 = 7.199, P = 0.027) but age, sex, and history of depression or anxiety did not improve model fit. Our findings indicate that family caregivers who cohabitate exhibit increased perception of sleep difficulty over the course of hospice. Future studies and interventions for hospice family caregivers' sleep should consider cohabitation between the patient and the caregiver as a significant predictor of sleep difficulty to observe and potentially mediate the negative outcomes associated with caregiver sleep difficulty. Further, determining the underlying reasons for sleep difficulty in cohabitation (e.g., patient symptoms or treatments) should be explored.

Performance evaluation of predictive models for detecting MMR gene mutations associated with Lynch syndrome in cancer patients in a Chinese cohort in Taiwan.

Identifying Lynch syndrome significantly impacts cancer risk management, treatment, and prognosis. Validation of mutation risk predictive models for mismatch repair (MMR) genes is crucial for guiding genetic counseling and testing, particularly in the understudied Asian population. We evaluated the performance of four MMR mutation risk predictive models in a Chinese cohort of 604 patients with colorectal cancer (CRC), endometrial cancer (EC), or ovarian cancer (OC) in Taiwan. All patients underwent germline genetic testing and 36 (6.0%) carried a mutation in the MMR genes (MLH1, MSH2, MSH6, and PMS2). All models demonstrated good performance, with area under the receiver operating characteristic curves comparable to Western cohorts: PREMM5 0.80 (95% confidence interval [CI], 0.73-0.88), MMRPro 0.88 (95% CI, 0.82-0.94), MMRPredict 0.82 (95% CI, 0.74-0.90), and Myriad 0.76 (95% CI, 0.67-0.84). Notably, MMRPro exhibited exceptional performance across all subgroups regardless of family history (FH+ 0.88, FH- 0.83), cancer type (CRC 0.84, EC 0.85, OC 1.00), or sex (male 0.83, female 0.90). PREMM5 and MMRPredict had good accuracy in the FH+ subgroup (0.85 and 0.82, respectively) and in CRC patients (0.76 and 0.82, respectively). Using the ratio of observed and predicted mutation rates, MMRPro and PREMM5 had good overall fit, while MMRPredict and Myriad overestimated mutation rates. Risk threshold settings in different models led to different positive predictive values. We suggest a lower threshold (5%) for recommending genetic testing when using MMRPro, and a higher threshold (20%) when using PREMM5 and MMRPredict. Our findings have important implications for personalized mutation risk assessment and counseling on genetic testing.

Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant-negative familial pancreatic cancer families.

To evaluate the diagnostic yield of pancreatic cancer screening in individuals at risk (IAR) from familial pancreatic cancer (FPC) families with respect to the presence or absence of pathogenic germline variants predisposing to pancreatic adenocarcinoma (PDAC). In a 20 years period, IAR from FPC families were enrolled in a prospective screening program of the national case collection for FPC of Germany, including magnet resonance imaging (MRI) and endoscopic ultrasound (EUS). The diagnostic yield was analyzed regarding significant pancreatic lesions such as PDAC, high-grade pancreatic-intraepithelial-neoplasia (PanIN3) and intraductal-papillary-mucinous-neoplasia (IPMN) with high-grade dysplasia. Screening results were compared between carriers of pathogenic variants and variant-negative IAR. 337 IAR, including 74 (22%) variant-carriers and 263 IAR of variant-negative FPC families (mean age 49; standard deviation [SD]+8.9) were followed 64 (SD+55) months. IAR underwent 5.1 (SD+3.9) screening visits with 1733 MRI (5.1,SD+3.9 per IAR) and 728 EUS (2.2,SD+1.7 per IAR). In 12 (4%) cases, significant pancreatic lesions were detected, including 4 PDAC, 3 PanIN3 and 5 high-grade IPMN. Three of 4 IAR with PDAC died after a mean of 27months postoperatively, and one IAR is alive without evidence of disease after 31months. The diagnostic yield for significant lesions was 13.5% (10/74) for variant carriers compared to 0.8% (2/263) for IAR of variant-negative FPC families (p<0.001). Logistic regression analysis revealed that a negative variant status was almost always accompanied by the absence of a significant lesion over time with a negative predictive value of 99.2% (95% CI 97.3%-99.9%). The diagnostic yield seems to justify PDAC screening in IAR of FPC-families with pathogenic germline variants in PDAC predisposing genes, not in IAR of variant-negative families.

The Epigenetic Modifiers HDAC2 and HDAC7 Inversely Associate with Cancer Stemness and Immunity in Solid Tumors.

Dysregulation of histone deacetylases (HDACs) is closely associated with cancer development and progression. Here, we comprehensively analyzed the association between all HDAC family members and several clinicopathological and molecular traits of solid tumors across 22 distinct tumor types, focusing primarily on cancer stemness and immunity. To this end, we used publicly available TCGA data and several bioinformatic tools (i.e., GEPIA2, TISIDB, GSCA, Enrichr, GSEA). Our analyses revealed that class I and class II HDAC proteins are associated with distinct cancer phenotypes. The transcriptomic profiling indicated that class I HDAC members, including HDAC2, are positively associated with cancer stemness, while class IIA HDAC proteins, represented by HDAC7, show a negative correlation to cancer stem cell-like phenotypes in solid tumors. In contrast to tumors with high amounts of HDAC7 proteins, the transcriptome signatures of HDAC2-overexpressing cancers are significantly enriched with biological terms previously determined as stemness-associated genes. Moreover, high HDAC2-expressing tumors are depleted with immune-related processes, and HDAC2 expression correlates with tumor immunosuppressive microenvironments. On the contrary, HDAC7 upregulation is significantly associated with enhanced immune responses, followed by enriched infiltration of CD4+ and CD8+ T cells. This is the first comprehensive report demonstrating robust and versatile associations between specific HDAC family members, cancer dedifferentiation, and anti-tumor immune statuses in solid tumors.

Double Heterozygosity for Germline Mutations in Chinese Breast Cancer Patients.

Double pathogenic mutations occurring in an individual are considered a rare event. The introduction of a multiple-gene panel at Hong Kong Hereditary Breast Cancer Family Registry has allowed the identification of pathogenic variants in multiple genes, providing more information on clinical management and surveillance to the proband and their family members. Breast cancer patients who are double heterozygous (DH) for different hereditary breast and ovarian cancer syndrome (HBCO)-related genes were identified from a cohort of 3649 Chinese patients. Nine patients (0.25%) were observed to have germline DH mutations in ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, and TP53. Three probands were diagnosed with unilateral breast cancer, two patients were diagnosed with bilateral breast cancer, and four patients had multiple primary cancers. The median age for breast cancer diagnosis was an early age of 36 years. Chinese DH carriers did not show worse phenotypes or have a significantly downhill clinical presentation. However, seven out of nine (77.8%) of our DH carriers harbored a BRCA1 mutation, and four of them (44.4%) developed bilateral breast cancer, suggesting Chinese DH individuals may have a higher chance of having bilateral breast cancer than other populations (p = 0.0237).

An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer

Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

Two Japanese families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A: a case report

BackgroundGermline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) (OMIM #155,601), which is associated with an increased risk of pancreatic ductal adenocarcinoma and melanoma. FAMMM has been reported globally, but it is quite rare in Japan. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.Case presentationThe first case is a 74-year-old woman with a diagnosis of pancreatic carcinoma with multiple liver metastases. She had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. Whole exon sequencing detected a germline CDKN2A variant evaluated as likely pathogenic. The results were disclosed to her daughters after she died, and the same CDKN2A variant was detected in one of the daughter. The daughter was referred to a nearby hospital for her clinical management. The second case is a 65-year-old man with pancreatic ductal adenocarcinoma. He had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. He underwent a comprehensive genomic profiling test using pancreatic cancer tissue, and detected a presumed germline pathogenic variant of CDKN2A. Germline testing confirmed the same CDKN2A variant. Genetic analysis of his relatives produced negative results. Other blood relatives are scheduled for genetic analysis in the future. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.ConclusionsIn current Japanese precision medicine, comprehensive genetic analysis can reveal rare genetic syndromes and offer us the opportunity to provide health management for patients and their relatives. However, gene-specific issues are raised in terms of the evaluation of a variant’s pathogenicity and the extent of surveillance of the at-risk organs due to a lack of genetic and clinical data concerning CDKN2A variant carriers in Japan.

Evolutionary history of adenomas to colorectal cancer in FAP families.

Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by multiple polyps at various evolutionary stages, which, if left untreated, inevitably progress to colorectal cancer (CRC). In this study, we present a comprehensive analysis of the evolutionary history of FAP-CRC from precancerous adenoma to carcinoma. Tissues were collected from gastrointestinal endoscopy or surgical resection. Exome sequencing was performed on multiple regions of adenocarcinoma (n = 8), villous adenoma (n = 10), tubular adenoma (n = 9) and blood samples were obtained from 9 patients belonging to 7 Chinese FAP families. Phylogenetic trees were reconstructed, and evolutionary analysis was conducted to reveal the temporal sequence of events leading to CRC. Inherited germline mutation sites in APC gene were identified in FAP01 (p.S1281*, COSM19212), FAP03 (p.S384Tfs*19), FAP04 (p.E1538*, COSM6041693), FAP05 (p.Q1062*, COSM3696862), and FAP07-FAP09 (p.V677Sfs*3). Notably, p.V677Sfs*3 mutation was recognized as a novel germline mutation in APC, supported by evidence of genotype-phenotype correlation in pedigree analysis. Adenomas exhibited lower mutational rates than FAP-CRC and displayed recurrent alterations in well-known chromosomal instability (CIN) genes (APC, RAS, SMAD4 and TP53) and DNA damage repair genes (SUZ12, KMT2C, BCLAF1, RUNX1, and ARID1B), suggesting the presence of genomic instability. Furthermore, a progressive increase in the HRD score (a measure of "genomic scars") was observed from tubular adenomas to villous adenomas and ultimately to carcinomas. TP53 emerged as the primary driver gene for adenoma-carcinoma transition, with driver mutations consistently appearing simultaneously rather than sequentially acquired from adenomas to carcinomas. Clonal evolution demonstrated that liver metastases can originate from the same cancer-primed cell present in a primary cancerous lesion. We identified a novel pathogenic variant in APC, namely, p.V677Sfs*3. The process of carcinogenesis in FAP-CRC supports the classical cancerization model, where an initial APC mutation leads to the activation of the WNT signaling pathway and CIN. Subsequently, additional mutations occur in other putative CIN genes (e.g., DNA repair, chromatin remodeling), ultimately leading to the development of microsatellite stable (MSS) tumors. Our study provides a comprehensive understanding of the genomic landscapes that underlie the transition from adenoma to carcinoma.

Incidence of Recurrence Post Hemi Thyroidectomy in Thyroid Papillary Carcinoma: A Meta-Analysis

Abstract Background Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. It has an excellent prognosis, with a 10-year survival rate of more than 95 per cent, although outcome is poorer for aggressive subtypes. Aim of the Work Our work in this study shows that the incidence of recurrence post hemi thyroidectomy is significantly higher compared to post total thyroidectomy and in case of multifocal and insular carcinoma with hemi thyroidectomy it increases the incidence of recurrence and drastically affecting the 10-year survival rate and the quality of life. Material and Methods We followed the PRISMA statement guideline during this systematic review and meta-analysis preparation and performed all steps according to the Cochrane handbook of systematic reviews of intervention. We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and Science Direct till November 2021 relevant keywords. We used the following search strategy for searching different databases: (“Papillary Thyroid Cancer” OR “Papillary Thyroid Cancers” OR “Papillary Thyroid Carcinomas” OR “Papillary Carcinoma Of Thyroid” OR “Papillary Thyroid Carcinoma” OR “Familial Non medullary Thyroid Cancer” OR “Non medullary Thyroid Carcinoma” OR “Non medullary Thyroid Carcinomas” OR “Thyroid Carcinoma, Non medullary” OR “Thyroid Carcinomas, Non medullary”) AND (Hemithyroidectomy OR Thyroidectomy OR Thyroidectomies OR thyroid removal). All the references of the included studies were searched for relevant studies. Results Multifocality and insular carcinoma and bilaterality increase the incidence of recurrence drastically so it is recommended for total thyroidectomy. Gender plays a role in the aggressiveness of the tumor but not in the incidence of recurrence as this is determined by the selection criteria of the candidate and the surgical technique. We studied 7 risk factors through this meta-analysis and it is recommended for application of LNR as a post op prognostic tool for recurrence and to apply hemi thyroidectomy for tumor size &amp;lt;2 cm instead of &amp;lt; 4 also meticulous pre-operative workup, accurate risk assessment, stratification and staging this is to customize a road map for every patient through a multi-disciplinary team. Conclusion In this meta-analysis we found that in low grade differentiated papillary thyroid carcinoma the recurrence is higher with hemithyroidectomy than in total thyroidectomy after applying the ATA guidelines for 10 years retrospectively but in case of 10 year survival it showed no significant difference.

Hereditary Colorectal Cancer: From Diagnosis to Surgical Options

AbstractHereditary colorectal cancer (CRC) syndromes account for up to 5% of CRC. Patients have an increased risk of CRC and extracolonic cancers, both of which develop at an early age. The main polyposis syndromes include familial adenomatous polyposis, MYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and PTEN hamartoma syndrome. The non-polyposis syndromes include Lynch syndrome and familial colorectal cancer type X. Each of the syndromes have distinct but sometimes overlapping phenotypes. Clinical evaluation and ultimately the underlying germline genetic pathogenic variants define the syndromes. Each syndrome has polyp, CRC, and extracolonic risks and management is based on early and timely surveillance with therapeutic and often extended prophylactic surgery. Surgical intervention strategies are individualized, considering not only the earlier onset of malignancies and heightened risks for metachronous cancers but also the patient's needs and quality of life. This article reviews the different diagnostic approaches to hereditary CRC and highlights subsequent disease-specific management and surgical decision-making strategies.

Exploring the genetic and epigenetic underpinnings of early-onset cancers: Variant prioritization for long read whole genome sequencing from family cancer pedigrees.

Despite significant advances in our understanding of genetic cancer susceptibility, known inherited cancer predisposition syndromes explain at most 20% of early-onset cancers. As early-onset cancer prevalence continues to increase, the need to assess previously inaccessible areas of the human genome, harnessing a trio or quad family-based architecture for variant filtration, may reveal further insights into cancer susceptibility. To assess a broader spectrum of variation than can be ascertained by multi-gene panel sequencing, or even whole genome sequencing with short reads, we employed long read whole genome sequencing using an Oxford Nanopore Technology (ONT) PromethION of 3 families containing an early-onset cancer proband using a trio or quad family architecture. Analysis included 2 early-onset colorectal cancer family trios and one quad consisting of two siblings with testicular cancer, all with unaffected parents. Structural variants (SVs), epigenetic profiles and single nucleotide variants (SNVs) were determined for each individual, and a filtering strategy was employed to refine and prioritize candidate variants based on the family architecture. The family architecture enabled us to focus on inapposite variants while filtering variants shared with the unaffected parents, significantly decreasing background variation that can hamper identification of potentially disease causing differences. Candidate d e novo and compound heterozygous variants were identified in this way. Gene expression, in matched neoplastic and pre-neoplastic lesions, was assessed for one trio. Our study demonstrates the feasibility of a streamlined analysis of genomic variants from long read ONT whole genome sequencing and a way to prioritize key variants for further evaluation of pathogenicity, while revealing what may be missing from panel based analyses.

Challenges Experienced by Saudi Patients With Cancer and Their Family Caregivers in Using Digital Healthcare Technology Platforms in the COVID-19 Pandemic.

COVID-19 has provided a unique boost to the use of digital healthcare technology, putting many vulnerable people at risk of digital exclusion. To promote digital healthcare equity, it is important to identify the challenges that may inhibit cancer patients and family caregivers from benefiting from such technology. This study explored the challenges that cancer patients and family caregivers experience in using digital healthcare technology platforms during the COVID-19 pandemic. A qualitative descriptive study using face-to-face semistructured individual interviews was carried out. A purposive sample of 21 participants was recruited from a public cancer hospital in Saudi Arabia. Qualitative content analysis with an inductive approach was utilized. The factors that challenged the ability of participants to benefit from digital healthcare technology were similar. Four themes related to the challenges the two groups experienced emerged: access to platforms, use of platforms for cancer health-related purposes, attitudes toward these platforms, and individual user preferences. This study identified numerous areas for improvement regarding digital healthcare technology platform implementation, which could increase future benefits and equal use. This study's findings also provide useful information to investigators who intend to create digital nursing interventions for both groups amid COVID-19 and other worldwide health crises.

Impact of genomic and epigenomic alterations of multigene on a multicancer pedigree.

Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated. This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B-cell acute lymphoblastic leukemia, B-ALL) in each of the three generations. Whole-genome sequencing and whole-exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole-genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B-ALL. According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G > A) and CFH (c.2314G > A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty-one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B-ALL. These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B-ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees.

Knowledge, attitudes and associated factors regarding cervical cancer and its screening practice among women of central Nepal

BackgroundCervical cancer is a severe public health problem worldwide including developing countries like Nepal. Cervical cancer screening has decreased the incidence and mortality of cervical cancer worldwide. Although it is highly preventable disease, cervical cancer is the leading cause of mortality among Nepalese women due to poor knowledge, negative attitude, poor practice, and late diagnosis. 1928 women died from cervical cancer in Nepal in 2018, this number was higher than that in 2017. ObjectivesThis study aimed to identify the knowledge, attitudes, and associated factors related to cervical cancer and its screening practices among women in Nepal. MethodsA community-based cross-sectional study was conducted after following the ethical approval from the Nepal Health Research Council, Ref No-115 in Kathmandu, Nepal. A total of 426 married women aged 18–49 were selected using a probability proportionate simple random sampling technique. After obtaining the written informed consent, the participants were interviewed using a validated questionnaire. Data entry and analysis were performed using IBM SPSS Statistics version 23, and we interpreted the findings using both descriptive and inferential statistics. To assess the factors associated with knowledge and attitude levels, we employed Chi-square analysis and subsequently conducted binary logistic regression analysis. ResultsThe average age of respondents was 31.18 ± 8.375 and 85 % of respondents heard about cervical cancer mainly from Television/Radio. Slightly more than half (51.8 %) of respondents had favorable attitude towards cervical cancer and its screening. Regarding knowledge, 46.5 % had adequate knowledge about cervical cancer and its screening. However, majority of (91.5 %) the respondents had never done cervical cancer screening test. In logistic regression analysis, respondent's education, occupation and heard about cervical cancer were significantly associated with adequate level of knowledge. Women with secondary education (AOR = 3.875 95 % CI: 1.741–8.623) and higher education (AOR = 7.818 95 % CI: 3.386–18.048) had more adequate knowledge compared with illiterate women. Age and heard about cervical cancer and type of family were positively associated with favorable attitude. There was a very weak positive correlation between knowledge and attitude of cervical cancer and its screening (r = 0.078). ConclusionCervical cancer is a severe public health problem of Nepal. From the result, we can say that about half of the subjects had knowledge and favorable attitude towards cervical cancer, despite the fact that still there is gap to transform it in to practice. There is a need for some measures to improve the cervical cancer screening practice by using information, Education, Communication materials and Behavior Change Communication (IEC/BCC)

Digital innovation for cancer risk assessment allows large-scale service redevelopment of regional cancer genetics service delivery.

Family-history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention and Early Detection (SPED). The online patient-facing cancer Family History Questionnaire Service (cFHQS) is a digitalised, resource efficient tool for family history data capture to facilitate this. The capturing of digital data from cFHQS allows for data interrogation of patients referred to Clinical Genetics for the purposes of service improvement. Digital data from 4,044 cFHQS respondents over a three-year period was collected and interrogated with respect to the number and type of familial tumour diagnoses to enable service improvement and streamlining of referral pathways. 81% of colorectal and 71% of breast screening assessments were population- or moderate-risk. Most patients who completed cFHQS reported more than one diagnosis of cancer/tumour/polyps in their family. 2.5% of family history assessment patients had a second indication that required assessment that would have been missed if single tumour type assessment was undertaken. Implementation of an innovative, digital family history data collection pathway has allowed large scale interrogation of referral patterns and assessment outcomes to enable service development. The high volume of inappropriate referrals to Clinical Genetics for population and moderate risk patients highlighted the need for dedicated secondary care pathway provision for these patients. The use of cFHQS streamlined family history assessment allows for redistribution of resources to improve equity and access to genetic cancer risk assessment.

Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendations.

The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS. Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC (BRCA1 and BRCA1) and LS (MLH1, MSH2, MSH6, PMS2, and EPCAM). Chart review was performed to collect demographics and personal and family cancer history. To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028). Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.

Cancer Family Members' Needs-Based Education in the Management of Anxiety: A Randomized Controlled Clinical Trial

Background: Understanding the information needs of caregivers in cancer care and managing their anxiety are crucial aspects of comprehensive nursing care. Nurses need to identify effective strategies to achieve this objective, yet there are limited studies in this area. Objectives: This study was designed to compare the effects of providing structured education versus needs-based education on the anxiety levels of cancer family members. Methods: In this randomized controlled trial, 80 primary caregivers of cancer patients were equally assigned to two study groups (group A: Education based on family members' needs, group B: Structured education) using a randomized minimization method. The Spielberger State-Trait Anxiety Inventory (STAI) was used for data collection. Data analysis employed descriptive statistics, Shapiro-Wilk test, chi-square test, Fisher’s exact test, Wilcoxon test, and Mann-Whitney U test at a significance level of 0.05. Results: The results indicated that the study groups were similar in terms of demographic characteristics. In group A, the mean ± SD of the STAI score was 54.2 ± 6.09 at baseline and decreased to 45.13 ± 3.87 after intervention (P = 0.001). In group B, the mean ± SD of the STAI score was 54.00 ± 4.92 at baseline and decreased to 51.68 ± 5.91 (P = 0.006). There were no statistically significant differences between the two groups at baseline (P = 0.872). However, a statistically significant difference in the STAI score was observed after intervention, and there was a significant difference in mean changes of the STAI score between groups (P = 0.001). Conclusions: Tailoring educational content according to the needs of cancer family members resulted in greater reductions in anxiety scores compared to the structured education method.

The Manchester Scoring System for predicting BRCA1/2 mutations underperforms in Arabic Omani breast cancer patients.

Risk assessment models that are applied to assess the lifetime risk of cancer and pathogenic variant risk are more commonly used in Western populations. Using these models, without validation, for non-Western populations has been questioned. This study aimed to evaluate the use and consistency of the Manchester Scoring System as a risk assessment model for the Omani population. A retrospective, file-based analysis was performed on breast cancer patients seen in a genomics department over a two-year period. Personal cancer history and family history were used to analyze the Manchester scores of 409 breast and/or cancer patients. The results show that, overall, the Manchester scores were low. If this risk assessment model had been used to determine eligibility for a priori service and genetic testing decisions, 12 BRCA pathogenic cases would have been missed. At this time, the Manchester Scoring System does not seem to be the best risk assessment model for use in the Omani population, unless the eligibility threshold of ≥6 is used, which could provide a better sensitivity for the Omani population. We propose using concepts of the Manchester Scoring model to create a scoring system that is more suitable for the Omani and Arabic population.

Hereditary Cancer Clinics Improve Adherence to NCCN Germline Testing Guidelines for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year overall survival rate of 10%. In November 2018, NCCN recommended that all patients with PDAC receive genetic counseling (GC) and germline testing regardless of family history. We hypothesized that patients with PDAC were more likely to be referred for testing after this change to the guidelines, regardless of presumed predictive factors, and that compliance would be further improved following the implementation of a hereditary cancer clinic (HCC). We conducted a single-institution retrospective analysis of patients diagnosed with PDAC from June 2017 through December 2021 at University of California, Irvine. We compared rates of genetics referral among patients in different diagnostic eras: the 18-month period before the NCCN Guideline change (pre-NCCN era: June 2017 through November 2018), 14 months following the change (post-NCCN era: December 2018 through January 2020), and 18 months after the creation of an HCC (HCC era: June 2020 through December 2021). Family and personal cancer history, genetics referral patterns, and results of GC were recorded. Data were compared using chi-square, Fisher exact, and multivariate analyses. A total of 335 patients were treated for PDAC (123 pre-NCCN, 109 post-NCCN, and 103 HCC) at University of California, Irvine. Demographics across groups were comparable. Prior to the guideline changes, 30% were referred to GC compared with 54.7% in the post-NCCN era. After the implementation of the HCC, 77.4% were referred to GC (P<.0001). The odds ratio (OR) for referral to GC among patients with a positive family history of cancer progressively decreased following the change (pre-NCCN era: OR, 11.90 [95% CI, 3.00-80.14]; post-NCCN era: OR, 3.39 [95% CI, 1.13-10.76]; HCC era: OR, 3.11 [95% CI, 0.95-10.16]). The 2018 updates to the NCCN Guidelines for PDAC recommending germline testing for all patients with PDAC significantly increased GC referral rates at our academic medical center. Implementation of an HCC further boosted compliance with guidelines.