Evaluation of germline genetic testing criteria in early-onset kidney cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 296-296
Author(s):  
Hong Truong ◽  
Rania Sheikh ◽  
Ritesh Kotecha ◽  
Yelena Kemel ◽  
Aliya Khurram ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Early Onset ◽  
Clear Cell ◽  
Cancer Susceptibility ◽  
Germline Variants ◽  
Panel Testing ◽  
Cancer Susceptibility Genes ◽  
History Of ◽  
Germline Testing

296 Background: An estimated 5% of kidney cancers are associated with hereditary RCC syndromes. Current germline genetic testing guidelines for patients with kidney cancer were developed to identify carriers of known RCC-associated genes and have evolved in the panel-testing era. We evaluated the utility of the recent National Comprehensive Cancer Network (NCCN) recommendation of testing all patients with early-onset RCC (defined as age of diagnosis ≤ 46 years) for germline variants in genes implicated in hereditary RCC syndromes. Methods: We retrospectively identified patients with RCC diagnosed at age ≤ 46 years who underwent targeted germline testing at our institution through referral to clinical genetics service (n = 68, 29%) or through broad germline testing of ≥77 cancer susceptibility genes using next generation sequencing as part of a prospective matched tumor-normal genomic profiling initiative (n = 165, 71%). Diagnostic performance of referral criteria was assessed by the presence of pathogenic/likely pathogenic (P/LP) germline variants in RCC-associated genes and incidental cancer susceptibility genes. Results: Of 233 patients, 61% were male, 74% were Caucasian, 15% had family history of RCC, 15% had RCC-syndromic features, including 9% with multifocal renal tumors. Most patients (54%) had clear cell RCC (ccRCC). P/LP germline variants were identified in 42 (18%) patients but only 21 (9%) had mutations in RCC genes (12 FH, 4 VHL, 2 SDHB, 1 each in BAP1, TSC1, and FLCN). All 21 early-onset patients with germline variants in an RCC-associated gene also had one of the following risk factors: non-ccRCC histology, family history, or syndromic features. In 91 patients (39%) with a non-RCC germline variants or no alteration, none of these three risk factors were found. Of 21 patients with non-RCC P/LP germline variants, 9 had mutations in moderate/high penetrance genes ( BRCA1 [2], ATM [2], CHEK2 [1], TP53 [2] , PALB2 [1], and RET [1]); 8/9 (89%) met standard criteria for testing for those genes independent of early-onset RCC diagnosis. Conclusions: Patients with early-onset clear cell RCC and no suspicious personal or family history are unlikely to have an RCC-associated germline mutation. RCC-gene panel testing has highest utility in early-onset patients with either non-ccRCC histology, family history of RCC, or RCC-associated syndromic features. Given the high frequency of non-RCC P/LP variants, early-onset RCC patients should be counseled regarding broader testing beyond RCC-associated genes.

scholarly journals The Characteristics of Risk Factors in Chinese Young Women with Acute Coronary Syndrome

2020 ◽  
Author(s):  
Ruifang Liu ◽  
Fangxing Xu ◽  
Yujie Zhou ◽  
Tongku Liu
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Young Women ◽  
Early Onset ◽  
Young Female ◽  
Cardiac Insufficiency ◽  
Control Group ◽  
Significant Difference ◽  
Gynecological Diseases ◽  
History Of

Abstract Background In recent years, the prevalence rate of ACS in Chinese young women has been increasing significantly, becoming the main cause of death in young female. This study aimed to investigate the characteristics and difference of risk factors in Chinese young women with ACS and to provide references for ACS prevention and treatment. Methods A 1:1 case-control study was conducted to evaluate risk factors of 415 young female patients with ACS (ACS group) who underwent PCI treatment and 415 young female cases without ACS (control group) who were hospitalized and confirmed by coronary angiography to exclude coronary heart disease from January 2010 to August 2016. The average age of the cases in the two groups was respectively (40.77±4.02) years-old and (40.57±4.01) years-old (P> 0.05). Results The risk factors in ACS group were overweight (64.10%), hypertension (49.88%), hyperlipidemia (35.66%), diabetes (23.37%), depression or anxiety disorder (16.62%), gynecological diseases (16.39%), Hyperuricemia (15.18%), family history of early onset coronary heart disease (14.94%), hyperhomocysteinemia (11.33%), hypothyroidism(14.96%), hypercholesterolemia (8.43%) and high c-reactive protein (7.47%), and were statistically significant difference (P<0.01) compared with that of control group. The average number of risk factors per case in ACS group was significantly more than that of control groups (P<0.01). There was a statistically significant difference in the number of combined risk factors of the overweight cases compared between two groups (P<0.01). Regression analysis showed that hyperlipidemia, hyperhomocysteinemia, overweight（obesity）, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases were independent risk factors (P<0.01). The bivariate correlation analysis between CRP level and age was r= -0.158 (P<0.01). This result showed the younger ACS patient is the higher serum CRP. Conclusion The independent risk factors of ACS in young women are hyperlipidemia, hyperhomocysteinemia, overweight, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases. The co-existence of multiple risk factors is the main cause suffering from ACS in young women.

HLA DQ2 HAPLOTYPE, EARLY ONSET OF GRAVES DISEASE, AND POSITIVE FAMILY HISTORY OF AUTOIMMUNE DISORDERS ARE RISK FACTORS FOR DEVELOPING CELIAC DISEASE IN PATIENTS WITH GRAVES DISEASE

2015 ◽  
Vol 21 (9) ◽  
pp. 993-1000 ◽  
Author(s):  
Piotr Miskiewicz ◽  
Agata Gos-Zajac ◽  
Alina Kurylowicz ◽  
Teresa Maria Plazinska ◽  
Maria Franaszczyk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Celiac Disease ◽  
Family History ◽  
Early Onset ◽  
Positive Family History ◽  
Autoimmune Disorders ◽  
Graves Disease ◽  
History Of ◽  
Hla Dq2

Confirmation of germline variants identified by tumor testing: A population-based study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13021-e13021
Author(s):  
Alexandra Pender ◽  
Aly Karsan ◽  
Stephen Yip ◽  
Ian Bosdet ◽  
Sean Young ◽  
...  
Keyword(s):  
Hereditary Cancer ◽  
Cancer Susceptibility ◽  
Population Based ◽  
Driver Mutations ◽  
Low Grade ◽  
Germline Variants ◽  
Referral Rates ◽  
Therapeutic Implications ◽  
Cancer Susceptibility Genes ◽  
Germline Testing

e13021 Background: Multi-gene panel tumour testing (TT) has been available in British Columbia since mid-2016 for metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), melanoma (MEL), low-grade glioma (LGG), and gastro-intestinal stromal tumours (GIST). TT can detect somatic driver mutations and potential pathogenic germline variants (pPGVs) associated with hereditary cancer susceptibility. We reviewed the frequency of pPGVs identified by TT and examined referral rates to the Hereditary Cancer Program (HCP) for confirmatory germline testing (GT) and therapeutic implications of PGV findings. Methods: All patients (pts) undergoing TT testing from October 1, 2016 to December 31, 2018 were identified. Diagnosis, age, gender, family history and treatment data were obtained. TT was performed by next-generation sequencing for all/selected regions of the following genes: AKT1, ALK, BRAF, BRCA1, BRCA2, CCND1, CCND3, CIC, EGFR, ERBB2, ERBB3, FUBP1, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MET, NRAS, PDGFRA, PIK3CA, PTEN, ROS1, SDHA, SDHB, SDHC, SDHD. Results: Among 2937 TTs, pPGVs were identified in 83 pts (2.8%) [Table 1]. 50 pts (57%) were referred to HCP, 41 had germline testing, and 14 PGV were confirmed. PGVs were most commonly identified in BRCA1/2 and SDHA and these findings did not influence oncologic treatments. Conclusions: TT detected pPGVs in 2.8% of unselected pts with metastatic cancers. Among 41 pts undergoing germline testing, 34% who would not have otherwise met testing criteria, had a confirmed PGV. Referral rates were low due to lack of patient and clinician awareness and poor health status. Although PGV findings did not directly impact treatment, TT identified 14 new families with hereditary cancer who can benefit from early detection and screening. Future directions include expansion of TT to include additional hereditary cancer susceptibility genes and development of digital tools for pts and clinicians. [Table: see text]

Risk factors for early-onset colorectal cancer in China.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10542-10542
Author(s):  
Zhe Pan ◽  
Junfeng Huang ◽  
Mingkai Huang ◽  
Zhiyuan Yao ◽  
Jiongqiang Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cohort Study ◽  
Family History ◽  
Early Onset ◽  
Cancer Site ◽  
Family History Of Cancer ◽  
History Of ◽  
Early Onset Colorectal Cancer ◽  
History Of Cancer

10542 Background: The incidence of colorectal cancer among persons aged < 50 years (early-onset colorectal cancer, EOCRC) has increased since the early 1990s. However, the risk factors contributing to this trend remain largely unknown. Methods: We conducted a retrospective study of participants who were aged < 50 years and without a previous cancer history, using the China Kadoorie Biobank cohort study. We analyzed data related to demographics, lifestyle habits, family history, and comorbidities of EOCRC cases with participants without colorectal cancer in this age group (controls). Univariate and multivariate-adjusted cox regression models were used to estimate the associations with risk factors. Results: We identified 225 EOCRC cases and 88842 controls that include the final analyses. Of the 225 EOCRC patients, 105 (46.7%) were colon cancers and 120 (53.3%) were rectum cancers. EOCRC cases were older, have more intake of fish and eggs, have higher BMIs, diabetes, and family history of cancer compared with controls (P < 0.05). After adjustment for potential confounding factors, increasing age (HR 2.18, 95%CI 2.05-2.31), BMI (HR 1.06, 95%CI 1.01-1.11), family history of cancer (HR 1.41, 95%CI 1.00-1.98), and more intake of fish (HR 1.54, 95%CI 1.09-2.19) were significantly associated with a higher risk of EOCRC. In sensitivity analyses stratified by cancer site (colon and rectum), the results remained consistent. Conclusions: Based on the large Chinese cohort study, we found increasing age, higher BMI or obesity, family history of cancer, and more intake of fish were independent risk factors for EOCRC. Further studies are needed to identify factors that cause the increasing incidence of EOCRC in China and other countries, and explore the potential mechanism behind.[Table: see text]

Germline alterations in cancer susceptibility genes in women with high-risk bladder cancer: Implications for germline testing and clinical management.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 418-418
Author(s):  
Hong Truong ◽  
Rania Sheikh ◽  
Aliya Khurram ◽  
Yelena Kemel ◽  
Andrew Thomas Lenis ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Germline Mutations ◽  
Susceptibility Genes ◽  
Stage At Diagnosis ◽  
Germline Variants ◽  
Cancer Susceptibility Genes ◽  
High Penetrance ◽  
Germline Testing

418 Background: Gender differences exist in bladder cancer incidence, stage at diagnosis, and outcomes. Women have lower incidence of bladder cancer but are diagnosed with more advanced disease at presentation. They also have less favorable outcomes even after adjusting for tumor stage and treatment modality. The biologic mechanisms underlying gender disparities in bladder cancer remain unknown. Methods: We leveraged a prospective matched tumor-normal genomic profiling initiative to determine the prevalence and spectrum of pathogenic/likely pathogenic (P/LP) germline variants in women with bladder cancer. Germline DNA was tested for mutations in ≥77 cancer susceptibility genes using next-generation sequencing in 686 patients with bladder cancer. Mutation frequency and clinical characteristics were assessed by gender. Results: A total of 184 (27%) women and 502 (73%) men with bladder cancer underwent germline testing; median age of diagnosis was 66 ± 11.3 and 65 ± 11.3 years, respectively. Twenty-two women (12%) had bladder cancer diagnosis at age ≤ 50 years. Both groups had similar rate of tobacco exposure (57% vs 63%, p = 0.1), family history of bladder cancer (10% vs 10%, p = 0.5), and disease stage at diagnosis (non-muscle invasive bladder cancer [NMIBC] 54% vs 54%, MIBC 38% vs 39%, and metastatic disease 8% vs 6%, p = 0.7). Women had more non-urothelial carcinoma histology than men (adenocarcinoma 5% vs. 1%; squamous cell carcinoma 1% vs 0.2%, p = 0.001). More P/LP germline variants were found in women than men (38 [21%] vs. 70 [14%], p = 0.04). Twenty-eight women (15%) had P/LP variants in DNA-damage repair (DDR) genes; 23 (13%) carried moderate/high penetrance germline mutations, the most common were BRCA1/ 2, CHEK2, NBN, ATM, and MITF. Current clinical guideline for referral for genetic testing failed to identify 12 (52%) women with moderate/high penetrance germline mutations. Nine women (5%) carried germline mutations associated with increased risk of ovarian/endometrial cancers ( BRCA1/ 2 [5], ATM [2], MLH1 [1], TP53 [1]). Conclusions: Deleterious germline alterations are commonly present in women with high-risk bladder cancer. The presence of germline variants in some genes, such as BRCA1/2, can guide cancer screening and risk-reducing surgeries for patients and their families. Women with high-risk bladder cancer should be evaluated for suitability of germline testing, especially those who desire preservation of uterus and ovaries at the time of radical cystectomy, to rule out the presence of P/LP variants that increase risk of future gynecologic malignancies.

Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes

2021 ◽  
Author(s):  
Anna M Varghese ◽  
Isha Singh ◽  
Rituraj Singh ◽  
Siddharth Kunte ◽  
Joanne F Chou ◽  
...  
Keyword(s):  
Early Onset ◽  
Pancreas Cancer ◽  
Cancer Susceptibility ◽  
Ductal Adenocarcinoma ◽  
Molecular Characteristics ◽  
Wild Type ◽  
Entire Cohort ◽  
Cancer Susceptibility Genes ◽  
Germline Variant ◽  
Germline Testing

Abstract Background Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report the epidemiologic, pathologic, and molecular characteristics of a patient cohort with early-onset pancreas cancer (EOPC). Methods Institutional databases were queried for demographics, treatment history, genomic results and outcomes. Overall survival (OS) from date of diagnosis was estimated using Kaplan-Meier method. Results Four hundred and fifty patients with EOPC were identified at Memorial Sloan Kettering between 2008 and 2018. Median OS was 16.3 months (95% confidence interval [CI] = 14.6 to 17.7 months) in the entire cohort and 11.3 months (95% CI = 10.2 to 12.2 months) for patients with stage IV disease at diagnosis. One hundred and thirty-two (29.3% of the cohort) underwent somatic testing; 21 of 132 (15.9%) had RAS wild-type cancers with identification of several actionable alterations, including ETV6-NTRK3, TPR-NTRK1, SCLA5-NRG1 and ATP1B1-NRG1 fusions, IDH1 R132C mutation, and mismatch repair deficiency. One hundred and thirty-eight (30.7% of the cohort) underwent germline testing; 44 of 138 (31.9%) had a pathogenic germline variant (PGV) and 27.5% harbored alterations in cancer susceptibility genes. Of patients seen between 2015 and 2018, 30 of 193 (15.5%) had a pathogenic germline variant. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared to patients without a PGV controlling for stage and year of diagnosis (hazard ratio = 0.42, 95%CI = 0.26 to 0.69). Conclusions PGVs are present in a substantial minority of patients with EOPC. Actionable somatic alterations were identified frequently in EOPC, enriched in the RAS wild-type subgroup. These observations underpin the recent guidelines for universal germline testing and somatic profiling in pancreatic ductal adenocarcinoma.

scholarly journals Cardiovascular Family History Increases the Risk of Disease Recurrence After a First Myocardial Infarction

2021 ◽  
Author(s):  
Agnes Wahrenberg ◽  
Ralf Kuja‐Halkola ◽  
Patrik K. E. Magnusson ◽  
Henrike Häbel ◽  
Anna Warnqvist ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Family History ◽  
Secondary Prevention ◽  
Risk Score ◽  
Early Onset ◽  
Disease Onset ◽  
Atherosclerotic Cardiovascular Disease ◽  
Net Reclassification Improvement ◽  
History Of

Background Family history of atherosclerotic cardiovascular disease (ASCVD) is easily accessible and captures genetic cardiovascular risk, but its prognostic value in secondary prevention is unknown. Methods and Results We followed 25 615 patients registered in SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) from their 1‐year revisit after a first‐time myocardial infarction during 2005 to 2013, until December 31, 2018. Data on relatives, diagnoses and socioeconomics were extracted from national registers. The association between family history and recurrent ASCVD was studied with Cox proportional‐hazard regression, adjusting for risk factors and socioeconomics. A family history of ASCVD was defined as hospitalization due to myocardial infarction, angina with coronary revascularization, stroke, or cardiovascular death in ≥1 parent or full sibling, with early‐onset defined as disease‐onset before 55 years in men and 65 in women. The additional discriminatory value of family history to Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was assessed with Harrell’s C‐index difference and reclassification was studied with continuous net reclassification improvement. Family history of early‐onset ASCVD in ≥1 first‐degree relative was present in 2.3% and was associated with recurrent ASCVD (hazard ratio [HR] 1.31; 95% CI, 1.17–1.47), fully adjusted for risk factors (HR, 1.22; 95% CI, 1.05–1.42). Early‐onset family history improved the discriminatory ability of the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, with Harrell’s C improving 0.003 points (95% CI, 0.001–0.005) from initial 0.587 (95% CI, 0.576–0.595) and improved reclassification (continuous net reclassification improvement 2.1%, P <0.001). Conclusions Family history of early‐onset ASCVD is associated with recurrent ASCVD after myocardial infarction, independently of traditional risk factors and improves secondary risk prediction. This may identify patients to target for intensified secondary prevention.

scholarly journals An unusual presentation of very early onset metastatic pancreatic adenocarcinoma in a young man: case report

2021 ◽  
Vol 8 (8) ◽  
pp. 2460
Author(s):  
Abhishek Arora ◽  
Ashesh K. Jha ◽  
Manoj Kumar ◽  
Manoj Kumar
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Early Onset ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Dilemma ◽  
Normal Limits ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
History Of ◽  
Abdominal Examination ◽  
Upper Abdomen

Pancreatic ductal adenocarcinoma (PDAC) is rare below 45 years of age and usually presents with constitutional symptoms, pain and jaundice. A 25 year old man, non-smoker, non-alcoholic presented to us with a lump in central upper abdomen of 1 month duration. Abdominal examination revealed a hard epigastric mass of size 7×10 cm. There were no other associated symptoms and no history of any similar illnesses in the family members. All laboratory parameters were within normal limits. Computed tomography showed a heterogeneous mass of size 7×13×15 cm arising from the head and neck of pancreas abutting the anterior abdominal wall with multiple abdominal and pelvic peritoneal deposits. Ultrasound guided core needle biopsy suggested PDAC. Hence, a diagnosis of very early onset metastatic PDAC was rendered and the patient was referred for palliative chemotherapy. PDAC below 45 years of age is known as very early onset PDAC. It is usually associated with family history of PDAC and known risk factors. This case was unique because of absence of the characteristic clinical features and known risk factors, early onset of occurrence and negative family history, which led to a diagnostic dilemma.

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