Positive Family History Of Cancer Research Articles

Patterns of screening and access to care in women diagnosed with breast cancer in a safety-net system.

1531 Background: Screening mammography reduces breast cancer specific mortality by allowing diagnosis at an earlier stage. Inconsistent guidelines and limitations in access to primary care are among factors that affect screening uptake. In this study, we reviewed patient characteristics, access to care, and uptake of screening mammogram (SMMG) prior to a breast cancer diagnosis at a safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County and is affiliated with the University of Texas Southwestern Simmons Comprehensive Cancer Center. Electronic medical records of patients with a new invasive breast cancer diagnosis between 2018 and 2019 at PH were reviewed and data on demographics and clinical presentation were collected. Patients were categorized based on SMMG uptake prior to their cancer diagnosis: never-screened, ever-screened (SMMG > 2 years prior to diagnosis) and recent-screened (SMMG within 2 years of diagnosis). Results: A total of 468 new breast cancer cases were identified (48.7% Hispanic; 32.9% Black). Of these, 12.2% were younger than 40 and 27.8% were 40-49. Payer mix included 64.7% uninsured and 34.8% Medicare/Medicaid. Half of the patients (50.6%) never had SMMG. Never-screened rate was higher among younger patients (98.2% in < 40; 53.8% in 40-49; and 39.4% in >50; p < 0.0001). Only 25.2% (118/468) of the patients had a SMMG within 2 years prior to their diagnosis. Among patients aged >40, 44.0% (181/411) were never-screened and 28.7% (118/411) were recent-screened. Screen-detection rate among patients >40 was 40.1% (165/411), of whom 22 (13.3% of screen-detects) were diagnosed with cancer on their first ever SMMG. Race/ethnicity, insurance status, and positive family history of cancer were not significantly different between never, ever, and recent-screened patients. Screening uptake correlated with nodal status, tumor size and stage at diagnosis. Patients who had a prior encounter at Parkland were more likely to have a SMMG. Patients established with Parkland primary care at diagnosis were more likely to have early-stage disease. In patients < 40, 24.6% presented with stage IV disease at diagnosis and 57.9% did not have a primary care provider. A positive family history of breast/ovarian cancer or any cancer was noted in 38.6% and 57.9% of patients < 40, respectively. Conclusions: In the cohort presented here, 27.8% of patients were between age 40-49, reflecting the impact of a gap in the guideline, which is now addressed in the most recent iteration of USPSTF guidelines. Connecting ED users to primary care, identifying higher risk individuals through family history, and increasing SMMG rate in the primary care setting are among strategies to reduce the rate of late-stage diagnosis of breast cancer, particularly among vulnerable patient populations.

Ethnic and clinical differences in gBRCA and HRD mutated breast and ovarian cancers and their response to PARP inhibitors.

e13102 Background: Hereditary mutations of the homologous recombination (HR), the key DNA double-strand break repair pathway, are one of the well-known causes of breast and ovarian cancers. Few reports exist on these mutations and the utilization of PARP inhibitors in the Middle Eastern region. Methods: This is a single-center retrospective study of breast and ovarian cancer patients who underwent genetic testing for g BRCA and HR defects (HRD) respectively between August 2021 and May 2023. Data was summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using RECIST criteria. Results: The prevalence of pathogenic mutations was 22.8%, with 26.3% of breast cancers harboring g BRCA mutations and 24% of ovarian cancers showing HRD positivity. Middle Eastern patients comprised 40% of the g BRCA-positive breast cancer group, while Asians accounted for 66% of the HRD-positive ovarian cancer patients. In mutated breast cancer, 53.3% had a positive family history of cancer. 33.3% of mutated breast cancer group and 66.6% of the ovarian cancer group received PARPis. Objective response to PARPi was 40% and 100% in breast and ovarian cancers, respectively. Conclusions: Our study revealed a high prevalence of g BRCA mutations (26.3%) in breast cancer and HRD positivity (24%) in ovarian cancer). Ethnic profiles differed between these cancers, with Middle Eastern and Southeast Asian patients dominating the breast and ovarian groups, respectively. Interestingly, the TNBC rate in breast cancer remained around 20% regardless of g BRCA status. While disparities between HRD groups were more pronounced in ovarian cancer, as expected, unexpected trends emerged in breast cancer. Further research with larger cohorts is needed to confirm these findings. [Table: see text]

Abstract PO4-10-10: NAVYA-AI enabled intervention to increase real-world guideline compliant care: Improving NGS testing in breast cancer

Abstract BACKGROUND: Navya-AI is a validated online cancer informatics solution that combines artificial intelligence based analysis of the guidelines and evidence, along with asynchronous expert review. Navya-AI releases preliminary system-generated opinions for patients whose treatment plans fit high confidence based on NCCN Guidelines and prior expert reviews. Prior research (SABCS 2014-2018 and ASCO 2021 showed: 1) 97% concordance of Navya-AI predictions with an academic medical center in India and in the US 2) 80% of patients implement treatment concordant with Navya-AI recommendations on the ground 3) Navya’s NCCN and evidence-based treatment plans reduce the patient waiting times for an expert opinion by an average by 3.5 days. Next generation sequencing (NGS) is an expensive but necessary method for identifying patients for risk reduction and therapy selection in breast cancer (BC). NGS testing can be over-used or under-used, and compliance with NCCN guidelines on patient selection is especially important in resource-constrained settings and Low Middle Income Countries (LMIC) such as India. The aim of this study is to find the physician compliance to NCCN guidelines on NGS testing in India, and how Navya-AI can identify the opportunity for improved care, and improve compliance with guidelines for optimal care. METHODS: From January 2022 to May 2023, Breast Cancer patients receiving Navya-AI treatment plan (based on guidelines and live expert-review) were analyzed. Patients who could afford NGS testing and targeted therapies, and who met the Enhanced tier of NCCN resource stratified guidelines for their care centers were identified. Their records were screened by Navya-AI to assess if they met NCCN criteria for NGS testing for risk reduction or for treatment selection (young age, positive family history, triple negative breast cancer etc.). Treating physicians were then analyzed if they had ordered NGS appropriately, or had missed an opportunity for NGS (undertreatment), or had over-ordered NGS (overtreatment).RESULTS: 521 BC patients who could afford NGS tests received a Navya-AI plan during this period. Of these, 85% were Indian patients (415/521) and were analyzed. Patients were diverse with respect to age,cancer stage, family history of cancer and histology: Age < 35: 6.7%, 35-50: 33%, 51-65: 43.76%, >65: 16.51%; early stage: 21.5%, locally advanced stage: 29.56%,metastatic stage: 47.79% and benign disease: 1%; positive family history of cancer: 37.35%, triple negative BC: 21.9%. Of 415 indian breast cancer patients who could afford testing, NGS testing was indicated in 69.64% (289/415) as per NCCN guidelines. The treating physician was compliant with NCCN guidelines in only 47.95% (199/415) of the cases: 19.2% (80/415) of the time, NGS was indicated and the treating physician ordered the same; 28.67% (119/415) of the time, NGS was not indicated, and the treating physician did not order NGS. The remaining 52% were not compliant with NCCN. Under-treatment was present in 50.36% (209/415) of cases, and was the vast majority of fallouts. Over-treatment was only present in 1.69% (7/415). In all 50.63% (209/415) cases, where NGS was not ordered by the treating oncologist, but was indicated, and affordable to the patient, Navya requested the patient to discuss the risks/benefits of NGS testing with their treating oncologist. CONCLUSION: NGS testing in BC patients has significant impact on risk-reduction, genetic counseling, choice of surgery, and treatment options for adjuvant therapy. Missed opportunities for NGS testing in more than 50% of the patients who can afford the testing and resultant therapies, points to a signficant area where compliance with guidelines and expert opinions can impact outcomes. A 'Technological Earthshot" that significantly increases adoption of guideline-based care is the first and an easy step towards 'Cancer Moonshots'. Citation Format: RA Badwe, Premal Thaker, Farzana Begum, Mayukh Acherjee, Gitika Srivastava, Naresh Ramarajan, Shona Nag, Sudeep Gupta, Seema Gulia, Jaya Ghosh, Bhawna Sirohi. NAVYA-AI enabled intervention to increase real-world guideline compliant care: Improving NGS testing in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-10.

Mismatch Repair Protein Deficiency in Triple Negative Breast Carcinomas: Clinicopathological Features

Abstract Introduction/Objective Female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer worldwide. Triple-negative breast cancer (TNBC) accounts for approximately 10–15% of all breast cancers. Chemotherapy remains the mainstay of systemic treatment for patients with TNBCs. Studies of mismatch repair (MMR) deficiency in TNBC reported variable prevalence ranging, from 0.2% to 18.6%. Recent studies described an excellent response in a patient with metastatic breast cancer treated with anti-PD1 illustrating the urgent need to test for MMRP deficiency as a predictive biomarkers to select those patients who could benefit from immunotherapy. The aim of the study is to detect MMRP deficiency in a cohort of TNBC Jordanian patients using the immunohistochemical methods. Methods/Case Report This study targeted cases of TNBC diagnosed and treated at King Hussein Cancer Center from 2015 until 2021. Clinicopathological data was obtained from 152 patients’ records. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma. Results (if a Case Study enter NA) The median age of patients at diagnosis was 49 years. A total of 14 out of 152 (9.2%) cases showed deficient MMR (dMMR) expression. Loss of expression of PMS2 was seen in 13 cases, 5 of which showed also loss of MLH1 expression. Loss of expression of both MSH6 and MSH2 was seen in one case. Positive family history of cancer was present in 5 of 12 patients with available data, three of whom had isolated loss of PMS2 and two had combined loss of PMS2 and MLH1. One pt. with loss of MSH6 and MSH2, had a personal history of a second malignancy (Lung cancer). The median duration of follow-up was 27 months. The overall (OS) and event- free survival (EFS) were better for dMMR despite the lack of statistically significant differences. At 24 months EFS and OS were 77.9% and 85.7% for dMMR and 63.9% and 56.9% for pMMR respectively. Conclusion The prevalence of dMMR in TNBC is 9% with most of the cases apparently related to Lynch syndrome. dMMR tumors tend to be associated with better outcomes compared to pMMR cases. dMMR can serve as a biomarker for better prognosis. These results are of value in directing the clinical management.

Association between a family history of cancer and multiple primary lung cancer risks: a population-based analysis from China

ObjectivesThe incidence of multiple primary lung cancer (MPLC) has increased in recent years. The risk factors of MPLC are not well studied, especially in the Asian population. This case-control study investigated the association between a family history of cancer and MPLC risk.MethodsWe used data from people who surgically confirmed MPLC with at least 2 nodes of Fujian Medical University Union Hospital and matched 1:2 normal individuals as controls between 2016 and 2017. Information on age, sex, lifestyle, personal history, and family history of cancer was collected using a self-administered questionnaire, and odds ratios (OR) were estimated using unconditional logistic regression.ResultsWe included 2 104 patients. In total, 321 patients with histologically confirmed MPLC and 642 healthy controls were studied. The significantly higher ratio of current smokers was observed for the cases than the controls (54.1% vs. 30.0%). A family history of LC in first-degree relatives of the cases reported a significantly higher proportion than in the controls (15.3% vs. 8.6%). Family history of all cancers and LC significantly increased the risk of MPLC (OR = 1.64, P = 0.009 and OR = 2.59, P = 0.000, respectively). The multivariate analysis identified a significantly increased risk of MPLC (OR = 2.45, P = 0.000) associated with parents and siblings influenced by LC history. The younger age (aged < 55 years) of LC cases at diagnosis exhibited a significantly increased risk of MPLC (OR = 2.39, P = 0.000). A significant association with a family history of LC was found for male squamous carcinoma and male adenocarcinoma (OR = 1.59, p = 0.037 and OR = 1.64, p = 0.032, respectively). A positive association with LC history was only observed for female adenocarcinoma (OR = 2.23, p = 0.028). The risk of MPLC was not significantly associated with A family history of cancers in non-smokers (OR = 0.91, P = 0.236). Ever-smokers with a positive family history of cancer or LC had a significantly elevated risk of MPLC (OR = 4.01, P = 0.000 and OR = 6.49, P = 0.000, respectively). We also observed a very elevated risk for smokers with no family history (OR = 3.49, P = 0.000). Such a positive association was also observed in ever-smokers with no family history of LC (OR = 3.55, P = 0.000). Adenocarcinoma in females was prevalent and significantly associated with a family history of LC in risk of MPLC compared with other histologic subtypes.ConclusionsOur findings suggest an association between a family history of LC and MPLC risk among an Asian population. Smoking status and family history of LC have a synergistic effect on MPLC. These findings indicate that MPLC exhibits familiar aggregation and that inherited genetic susceptibility may contribute to the development of MPLC.

Family history of cancer as a potential risk factor for colorectal cancer in EMRO countries: a systematic review and meta-analysis

The current meta-analysis aims to investigate the existing articles that evaluated the implications of a positive family history of cancer on the risk of colorectal cancer (CRC) within the EMRO countries. We employed PubMed, Scopus, and Web of Science as search databases for this study. To assess the quality of the selected articles, we utilized the Newcastle–Ottawa (NCO) checklist. In comparing the impact of a family history of cancer between the case and control groups, we computed the odds ratio (OR) along with its corresponding 95% confidence interval (CI). Finally, 27 articles were selected for meta-analysis. The result of the meta-analysis showed a significant association between the presence of a family history of CRC or any cancers and CRC (OR 2.21; 95% CI 1.54–3.17; P < 0.001, OR 1.76; 95% CI 1.27–2.42; P = 0.001, respectively). Our findings underscore the critical importance of timely screening and early identification for individuals with a family history of cancer. By fostering close coordination among healthcare facilities and actively promoting the adoption of screening methods for early detection, we have the potential to significantly reduce both mortality rates and financial burdens of CRC on the general public, ultimately leading to enhanced patient outcomes.

Optical genome mapping identifies structural variants in potentially new cancer predisposition candidate genes in pediatric cancer patients.

Genetic predisposition is one of the major risk factors for pediatric cancer, with ~10% of children being carriers of a predisposing germline alteration. It is likely that this is the tip of the iceberg and many children are underdiagnosed, as most of the analysis focuses on single or short nucleotide variants, not considering the full spectrum of DNA alterations. Hence, we applied optical genome mapping (OGM) to our cohort of 34 pediatric cancer patients to perform an unbiased germline screening and analyze the frequency of structural variants (SVs) and their impact on cancer predisposition. All children were clinically highly suspicious for germline alterations (concomitant conditions or congenital anomalies, positive family cancer history, particular cancer type, synchronous or metachronous tumors), but whole exome sequencing (WES) had failed to detect pathogenic variants in cancer predisposing genes. OGM detected a median of 49 rare SVs (range 27-149) per patient. By analysis of 18 patient-parent trios, we identified three de novo SVs. Moreover, we discovered a likely pathogenic deletion of exon 3 in the known cancer predisposition gene BRCA2, and identified a duplication in RPA1, which might represent a new cancer predisposition gene. We conclude that optical genome mapping is a suitable tool for detecting potentially predisposing SVs in addition to WES in pediatric cancer patients.

Clinicopathological Comparison of Colorectal Cancer in Young and Old Patients

Background &amp; Objectives: Colorectal cancer is the commonest malignancy in the gastrointestinal tract third and the second leading cause of cancer death worldwide. The advanced stages and poor tumor grade of colorectal cancer are likely to be found in younger patients than in older one. The aim of our study was to study the various demographic features that are known to influence developing colorectal cancer and to compare clinicopathological features of colorectal cancer between young and old patients. Methods: This is a retrospective study, conducted over the period from 2015- 2020, where we reviewed medical files, histopathological reports and radiological findings of 200 newly diagnosed colorectal cancer cases that were admitted to Rizgari Hospital/ Clinical Oncology Department, Erbil, Kurdistan of Iraq. The patients aged below 40 years were classified as the “young group”, and those aged 60 years and more were classified as the “old group”. The clinicopathological features in both groups had been compared. Results: The young group and old group consisted of (60) 30% and (140) 70% of patients, respectively. The young group showed a higher percentage of positive family history of cancer in comparison to the old one, and BMI also was statistically significant. Regarding the histopathological grading and pathological staging: grade -II was the most common, (82%) in both groups, and stage III &amp;IV were significantly higher in the young group (83.3%) in comparison to the old group (74.3%).

Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.

Evaluation of anxiety and depressive symptoms in a sample of adult patients with cancer at Al-Furat Cancer Hospital/Najaf

Abstract Background: Cancer patients’ mental well-being negatively impact on treatment tolerance, reduces the effectiveness of chemotherapy, prolong hospitalization, increase healthcare cost, would lower life expectancy, and poor quality of life. Objectives: The objectives are to evaluate the rate of anxiety and depressive symptoms across adult cancer patients and to find its association with some sociodemographic factors. Materials and Methods: A cross-sectional study was carried out in Al-Furat Cancer Hospital in Najaf/Iraq, from April 10 to July 10, 2022. All convenient patients who were admitted to the hospital during the study period were included. The data were collected by interviewing the patient using semiconstructed questionnaire, and Hospital Anxiety and Depression Scale was used. Chi-square and independent t tests were used. Results: Among a total of 470 patients, the mean age was 54.1 ± 14.2 years, 284 (60.4%) were female, and 364 (77.4%) were married. About 183 (38.9%) patients had anxiety disorder, and there was a significant association among gender, marital state, occupation, presence of pain, and having gynecological cancers with anxiety. Around 163 (34.7%) of patients had depressive symptoms. The study showed a significant association among gender, occupation, low income, and the presence of a positive family history of cancer, metastasis, and pain with depression. Conclusions: More than one-third of the sample suffered from anxiety and depression; females more than males. There was a significant association between anxiety/depression and gender, occupation, and presence of pain.

Missing a chance to prevent: disparities in completion of genetic evaluation in high-risk patients with endometrial cancer.

The primary goal of this study is to examine disparities in high-risk endometrial cancer (EC) patients in relation to rates of genetic referrals (GR), testing (GT), and counseling (GC). This is a retrospective analysis of patients with newly diagnosed EC between January 1, 2014 and September 1, 2020 at a single institution. Patients were defined as high-risk EC patients when they were 1) diagnosed at 50 years or younger, 2) had a positive family history for cancer or 3) had evidence of loss of mismatch repair protein expression on tumor immunohistochemistry. Rates of GR, GT and GC were analyzed based on race, ethnicity, primary language and insurance status. During the study period, 674 patients were diagnosed with EC and 249 (36.9%) were considered high-risk EC patients. Among high-risk patients, 128 (51.2%) were referred to GT and GC. Of those referred, 103 (80.5%) underwent GT and 85 (66.4%) completed GC. Out of all high-risk patients, 20 (18.4%) were positive for LS on GT and 29 (28.2%) had VUS results. In multivariate analysis, the odds of GT and GC referral were lower among patients who identified as Hispanic (OR=0.40; 95% CI=0.19-0.87; p=0.020). Patients who identified as black were less likely to receive GC when compared to patients of other races (p=0.030). It is our hope that through this data we will increase awareness around existing disparities in genetic evaluation for patients with EC and ultimately create strategies to improve equitable access to care for all patients.

Expression of VEGF in breast cancer

Background: To evaluate the expression of Vascular Endothelial Growth Factor in breast cancer patients. Materials &amp; methods: A total of 40 patients were enrolled. Mean age of the patients was 47.5 years. Biopsy specimens were obtained and were subjected with H and E staining. For VEGF marker, IHC staining was done. Segregation of subjects was done on the basis of VEGF expression. Univariate analysis was done for assessing the factors associated with positive expression of VEGF in breast cancer. All the results were recorded and were analysed using SPSS software. Results: A total of 40 patients were enrolled. Mean BMI was 25.5 kg/m2 . Majority had a positive expression of VEGF. Positive smoking history with positive VEGF was 20 and showed significant p- value. Positive family history of cancer and mean tumour size were also significant. Conclusion: Breast cancer patients are associated with enhanced expression of VEGF.

IBCL-301 Primary Extranodal Marginal Zone B-Cell Lymphoma Located in the Lower Eyelid Case Treated With Rituximab

The majority of lymphoma cases are accompanied by painless enlargement of several cervical lymph nodes. However, its primary site may be also extranodal and unusual in some cases. Sharing an unusual case report of primary lower eyelid extranodal marginal zone B-cell Lymphoma treated with rituximab. A case report. In January 2021, a 53-year-old woman was admitted to our clinic with a subcutaneous change in her lower eyelid. The patient had a history of hypertension and had undergone IVF several years ago. There was a positive family history of cancer. There were no palpable lymph nodes in the periphery in physical examination. The hemogram and laboratory examinations were normal, as was the abdominal echo examination. An MRI scan of the cranium/orbits revealed the presence of a mass with a size of 15×8×13mm in the canthal angle/lower right cover OD, with no signs of intra-bulbar infiltration. A mass biopsy was performed, and the HP diagnosis revealed an extranodal marginal zone B-cell lymphoma (CD20+) (Bcl2+) (CD138+). Once the nature of the disease and the location of the mass had been determined, treatment with Rituximab 375mg/m2 every 28 days was planned. After 10 cycles of treatment, a PET-CT scan was performed, and a small region with low metabolic activity SUV max 3.0 was detected retrobulbar laterally on the right side. A cranial MRI scan revealed no evidence of recurrence or other pathological signs. The laboratory, abdominal, and neck echo exams were all normal. The patient's condition remains stable despite receiving rituximab 375 mg/m2 every two months, with no signs of disease and a normal MRI scan. The prognosis of this type of tumor is difficult to predict because the long-term response to the primary treatment must be closely monitored.

Pattern of Clinicopathological Features of Head and Neck Cancer Patients in a Tertiary Level Specialized Hospital in Dhaka, Bangladesh

A cross-sectional, descriptive study was conducted to see the pattern of clinicopathological features of head and neck cancer patients in a tertiary level hospital. The study was conducted between January and April of 2017 in National Institute of Cancer Research &amp; Hospital (NICRH), Dhaka, Bangladesh. Data was collected from a total number of 69 histopathologically and clinically confirmed patients. A male predominance (2.14:1) was noted except for oral cavity cancer (1:1). Mean age for males and females were (56.15±11.47) years and (54.50±7.16) years respectively. Positive history of associated factors like smoking (60.34%), betel nut and betel leaf (81.36%), smokeless tobacco (56.90%) was prevalent among majority of the participants except for alcohol (6.90%). Smoking was prevalent only among males. Knowledge regarding the role of associated factors was very poor, e.g., smoking (10.61%), betel nut &amp; leaf (7.58%), smokeless tobacco (6.06%), alcohol (7.58%) for causing cancer. 10.71% patients gave positive family history of cancer (1st degree relative). 27.59% patients gave history of treatment by homeopathy/traditional healers. The most common sites of cancer in males were larynx (27.3%) followed by oral cavity (20.5%). In case of female patients, most common sites were oral cavity (40.9%) followed by larynx (22.7%). Most common histopathological type was squamous cell carcinoma (91.94%). Lymph node metastasis were present in 47.62% patients, whereas only 1.56% patients had distant metastasis and 3.13% had recurrent/residual disease. 18.64% patients gave history of definitive surgery. To conclude, most of the patients usually reported with advanced stages of cancer; however, preventable factors were found among all of them. Unfortunately, they had very poor knowledge about those preventable factors which warrants an immediate and elaborate public health program to fill up this vast gap of knowledge. Prevention and early diagnosis should be main arsenal to combat head and neck cancer.&#x0D; CBMJ 2022 July: vol. 11 no. 02 P: 108-113

Body Mass Index and Other Risk Factors Effects on Colon Cancer Prognosis in Pakistan.

Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC). A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2) and overweight (≥25 Kg/m2). Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20-85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer. Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

A case\u2013control study of BRCA1 founder mutations 185delAG and 5382insC in a cohort of Egyptian ovarian cancer patients using pyrosequencing technique

BackgroundOvarian cancer (OC) is considered a leading cause of death among women with gynecological malignancies. OC, like breast cancer, shows a familial predisposition to germline mutations in genes BRCA1 or BRCA2, which have proved to play important roles in the incidence and progression of cancers. In Arab countries there are limited data concerning BRCA1 or BRCA2 founder mutations associated with familial ovarian cancer (FOC). Therefore, the aim of this pilot study was to assess two common founder mutations of BRCA1 (185delAG and 5382insC) in a cohort of Egyptian patients with FOC. The study included fifty female patients with FOC and twenty healthy controls. Clinical, laboratory, and pathological findings were assessed as well as response to therapy. Genetic testing for BRCA1 (185delAG and 5382insC) mutations was performed on peripheral blood samples using a short-fragment sequencer (pyrosequencer).ResultsThe BRCA1 185delAG mutation was not observed in either the FOC patients or the controls. However, the carrier frequency of heterozygous BRCA1 5382insC mutation was 8%. All the FOC patients with a BRCA1 5382insC mutation had a positive family history of cancer (p = 0.009). All carriers of the BRCA1 5382insC mutation showed a preliminary good response to chemotherapy. The majority of carrier patients were diagnosed at an advanced stage of the disease with high-grade tumors and distant metastasis (75% of cases).ConclusionThe frequency of the BRCA1 5382insC mutation in FOC patients was 8%. The strong association between the mutation and the positive family history suggests that a wider screening for BRCA1 founder mutations would be valuable in predicting high-risk individuals.

Pituitary tumors and the risk of other malignancies: is the relationship coincidental or causal?

Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and ACTH-secreting adenomas. Most pituitary adenomas seem to be sporadic and their persistent growth is very atypical. No molecular markers predict their behavior. The occurrence of pituitary adenomas and malignancies in the same patient can be either pure coincidence or caused by shared underlying genetic susceptibility involved in tumorigenesis. Detailed family history on cancers/tumors in the first, second and third generation of family members on each side of the family has been reported in a few studies. They found an association of pituitary tumors with positive family history for breast, lung and colorectal cancer. We have reported that in about 50% of patients with pituitary adenomas, an association with positive family history for cancer has been found independent of secretory phenotype (acromegaly, prolactinoma, Cushingʼs disease or non-functioning pituitary adenomas). We also found earlier onset of pituitary tumors (younger age at diagnosis of pituitary tumors) in patients with a strong family history of cancer. In our recent unpublished series of 1300 patients with pituitary adenomas, 6.8% of patients were diagnosed with malignancy. The latency period between the diagnosis of pituitary adenoma and cancer was variable, and in 33% of patients, it was longer than 5 years. Besides the inherited trophic mechanisms (shared underlying genetic variants), the potential influence of shared complex epigenetic influences (environmental and behavioral factors – obesity, smoking, alcohol intake and insulin resistance) is discussed. Further studies are needed to better understand if patients with pituitary adenomas are at increased risk for cancer.

Screening of Lynch syndrome in endometrial cancer in Iranian population with mismatch repair protein by immunohistochemistry.

Lynch syndrome (LS) is one of the commonest genetic cancer syndromes, with an incidence rate of 1 per 250-1000 population. The aim of this study was to evaluate the frequency and characteristics of MMR deficiency in endometrial cancer in Iranian women. One hundred endometrial carcinoma cases who referred to the gynecological oncology clinic of Imam Hossein Medical Center located in Tehran, Iran, from 2018 to 2020 were included in the study. Immunohistochemistry (IHC) evaluation was performed mainly on the hysterectomy specimens of all endometrial cancer (EC) patients to assess MMR proteins (MLH1, MSH2, MSH6, and PMS2) expression. A total of 23 out of 100 (23%) cases were identified through IHC screening to be MMR-deficient. The most common types were loss of MLH1/PMS2 (17.4%) and solitary MSH2 (17.4%) expressions followed by PMS2/MSH2 loss (13%). MMR deficiency (dMMR) histopathology was significantly overrepresented in patients with family history of cancer or Lynch syndrome (LS) associated cancers (p-values of 0.016 and 0.005, respectively). The rate of myometrial invasion and lower uterine segment involvement were also significantly higher in dMMR EC patients compared to MMR-intact EC (p-value of 0.021 and 0.018, respectively). MMR deficiency, observed in 23% of endometrial cancer cases, was associated with higher rates of poor prognostic factors including myometrial invasion and lower uterine segment involvement. The presence of positive family history of cancer and family history of LS-associated cancer increased the probability of MMR-deficiency in endometrioid endometrial cancer to 47% and 70%, respectively.

The role of family history of Cancer in Oral Cavity Cancer

ObjectivesOral and oropharyngeal squamous cell carcinoma (SCC) is the 10th most common cancer in the United States (8th in males, 13th in females), with an estimated 54,010 new cases expected in 2021, and is primarily associated with smoked tobacco, heavy alcohol consumption, areca nut use and persistent high-risk human papillomavirus (HPV). Family history of cancer (FHC) and family history of head and neck cancer (FHHNC) have been reported to play an important role in the development of OSCC. We aimed to investigate the role of FHC, FHHNC and personal history of cancer in first/second degree-relatives as co-risk factors for oral cancer.MethodsThis was a retrospective study of patients diagnosed with OSCC at the Division of Oral Medicine and Dentistry at Brigham and Women’s Hospital and at the Division of Head and Neck Oncology at Dana Farber Cancer Institute. Conditional logistic regressions were performed to examine whether OSCC was associated with FHC and FHHNC of FDRs and SDRs, personal history of cancer and secondary risk factors.ResultsOverall, we did not find an association between FHC, FHHNC and OSCC risk, whereas patients with a cancer history in one of their siblings were 1.6-times more likely to present with an OSCC. When secondary risk factors were considered, patients with a history of oral leukoplakia and dysplasia had a 16-times higher risk of having an OSCC.ConclusionsOur study confirmed that a previous history of oral leukoplakia or dysplasia was an independent risk factor for OSCC. A positive family history of cancer in one or more siblings may be an additional risk factor for OSCC.

Factors associated with PSA testing in men ≥ 50 years in Ireland

Abstract Background Ireland has among the highest rates of prostate cancer in the EU, primarily due to widespread PSA screening. PSA screening is not recommended for asymptomatic men. Due to the potential for harm to the patient, and the economic and clinical repercussions for the healthcare system caused by inappropriate screening, this study aimed to investigate associations between PSA screening and sociodemographic, lifestyle, and health-related factors in men ≥50 years in Ireland. Methods A cross-sectional study was completed using data from Wave 4 of The Irish Longitudinal Study on Aging (TILDA), a nationally representative sample of community dwellers ≥ 50 years in Ireland. Participants self-reported having or not having a PSA test to screen for prostate cancer in the previous two years. Variables were entered into a multivariable logistic regression to estimate adjusted odds ratios (OR) for associations between PSA testing and the factors of interest. Results There were 2,426 male participants, with 68% reporting a PSA test in the previous two years. In adjusted analysis, older age (OR 1.78, 95%CI 1.32-2.31), third level education (OR 1.34, 95%CI 1.07-1.69) and a higher household net income (OR 2.14, 95% CI 1.52-3.02) increased the likelihood of PSA testing. Health-related factors positively associated with PSA testing screening were private health insurance (OR 1.89, 95%CI 1.52-2.35), blood pressure measurement in the previous year (OR 8.80, 95%CI 6.06-12.77) and a positive family history of cancer (OR 1.42, 95%CI 1.13-1.78). Conclusions High rates of prostate cancer screening are taking place in Ireland, despite the absence of a population-based screening programme. Men of older age, higher socioeconomic status and who demonstrate health-protective-behaviours have an increased risk of PSA screening. This subgroup of the population should be targeted to increase awareness of the potential benefits and harms of PSA testing. Key messages Rates of PSA screening remain high in Ireland, despite the absence of a population-based screening programme. Increased awareness of the potential harms and benefits of PSA screening is needed.