Germline pathogenic variants of the RPS20 (ribosomal protein S20) gene are suspected to be involved in the predisposition to familial colorectal cancer (CRC) with no DNA mismatch repair deficiency. RPS20 pathogenic varia...Germline pathogenic variants of the RPS20 (ribosomal protein S20) gene are suspected to be involved in the predisposition to familial colorectal cancer (CRC) with no DNA mismatch repair deficiency. RPS20 pathogenic variants are very rare with only five reported cases in the literature. We report in this work the retrospective germline analysis of RPS20 for 1035 consecutive patients with a personal and/or familial history suggestive of hereditary predisposition to CRC. Within this series, a pathogenic variant in known CRC genes was found in 15% of cases and we describe one RPS20 loss-of-function variant (NM_001146227.1:c.115_116del, p.(Leu39Aspfs*33)). This frameshift is the first reported de novo variant in CRC, it was identified in in a female patient diagnosed with rectal cancer at the age of 35, 11 adenomatous polyps in 5 years and breast cancer at the age of 43. RPS20 has an intriguing role in oncogenesis, acting as an oncogene or tumour suppressor depending on the context, and is also involved in Diamond-Blackfan anemia via gain of function or dominant negative variants. This is therefore a complex gene for genetic counselling and, given the rarity of RPS20 pathogenic variants, we emphasise the need to collect data to clarify the phenotypic spectrum of RPS20-associated cancers and thus improve management.
Boedec M, Aucouturier C, Cavaillé M
… +15 more, Leman R, Castéra L, Delhomelle H, Uhrhammer N, Bernard V, Giraud S, Lasseaux E, Jones N, Bidart M, Boutry-Kryza N, Noguès C, Colas C, Maugard C, Krieger S, Bouras A
PTEN Hamartoma Tumor Syndrome (PHTS) is an autosomal dominant disorder characterized by high penetrance and significant phenotypic variability. In most patients, targeted high-throughput sequencing (HTS) approaches enabl...PTEN Hamartoma Tumor Syndrome (PHTS) is an autosomal dominant disorder characterized by high penetrance and significant phenotypic variability. In most patients, targeted high-throughput sequencing (HTS) approaches enable the detection of loss-of-function pathogenic variants in PTEN, a tumor suppressor gene acting as a negative regulator of the PI3K-AKT pathway. We describe a patient exhibiting a clinical phenotype strongly indicative of PHTS, yet lacking a molecular diagnosis through PTEN-targeted HTS. After several years of diagnostic uncertainty, trio whole genome sequencing (WGS) ultimately identified a de novo germline deep intronic 98 bp deletion in PTEN intron 5 (c.492 + 1671_492 + 1768del). Targeted RNA sequencing revealed the inclusion of a pseudoexon, resulting in a frameshift and predicted protein truncation at codon 171 (p.Val166Asnfs*6). These data underline the importance of WGS approaches in detecting deep intronic structural variants, that may be overlooked by conventional methods.
Germline variants in RUNX1 and DDX41 are well-established contributors to hereditary myeloid neoplasms and are increasingly recognized as critical predisposing factors in the developing myelodysplastic syndromes (MDS) an...Germline variants in RUNX1 and DDX41 are well-established contributors to hereditary myeloid neoplasms and are increasingly recognized as critical predisposing factors in the developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This case report details a 51-year-old male diagnosed with MDS with excess blasts-1 (MDS-EB1), who harbored a rare combination of pathogenic germline variants in RUNX1 and a novel potentially pathogenic variant in DDX41 variant, alongside a somatic DDX41 mutation. The coexistence of these germline variants highlights the genetic complexity underlying hereditary myeloid neoplasms and reinforces the necessity of comprehensive genomic testing to ensure accurate diagnosis and informed clinical management. The interplay between RUNX1 and DDX41 variants may drive leukemogenesis, with the germline RUNX1 variant potentially fostering a cellular environment that enables the acquisition of somatic DDX41 mutations, leading to hematological malignancies. Conversely, the germline DDX41 variant may disrupt hematopoiesis and, when combined with RUNX1 dysfunction, contribute to disease progression. This case underscores the importance of screening germline variants in patients with myeloid neoplasms. It emphasizes the need to confirm the origin of these variants in non-hematopoietic tissues, such as fibroblasts (gold standard), to avoid misinterpretation caused by clonal hematopoiesis. Further research is warranted to elucidate the molecular mechanisms driving the interaction between RUNX1 and DDX41 variants and their collective impact on disease progression, treatment outcomes, and familial risk.
Familial adenomatous polyposis is an inherited genetic disorder responsible for multiple anomalies. Lifelong surveillance protocols are essential to detect and prevent adverse developments. However, limited data exist re...Familial adenomatous polyposis is an inherited genetic disorder responsible for multiple anomalies. Lifelong surveillance protocols are essential to detect and prevent adverse developments. However, limited data exist regarding the long-term feasibility of such programs. This study aims to evaluate the compliance with a surveillance program for patients with familial adenomatous polyposis. The study collated data from all patients who underwent surgery between January 1981 and December 1993, excluding non-French residents. Recorded characteristics included medical history, follow-up results, the indications for operations or other procedures, outcomes of these interventions, and patient status at the end of the follow-up period. One hundred and sixty-four patients were enrolled, comprising 86 females (52.4%). The median age at the time of colorectal resection was 29.6 years [10-67]. Thirty-six (22.0%) were diagnosed with cancer at the time of their surgery. Fifty-eight patients (35.3%) passed away at a median age of 52 years [18-95]. During the follow-up period, 47 patients developed duodenal or reservoir adenomas requiring invasive procedures, or desmoid tumors necessitating treatment. After a possible 30 years of follow-up, 49 survivors (46.2%) are still under observation, while 57 (53.8%) have been lost to follow-up. After 30 years of follow-up, the survival rate was 74.2% for patients who remained under observation, but only 58.2% for those lost to follow-up. Long-term follow-up of patients with familial adenomatous polyposis is associated with a high rate of loss to follow-up. However, those who remain under observation maintain an excellent prognosis. Understanding the reasons for loss to follow-up is challenging but may help in reducing this high attrition rate.
Perivascular epithelioid cell tumors (PEComas) belong to a family of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. Li-Fraumeni syndrome (LFS), an...Perivascular epithelioid cell tumors (PEComas) belong to a family of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. Li-Fraumeni syndrome (LFS), an autosomal dominant cancer predisposition syndrome, is caused by a germline variant of the tumor suppressor gene TP53. Here, we report the case of a 20-year-old woman with LFS who developed a PEComa of the liver. She was suspected to have LFS because she had developed osteosarcoma (OS) of the femur along with a concurrent transitional liver cell tumor in the right liver lobe at the age of 8 years. She also tested positive for the germline TP53 missense variant c.722 C > T (p.Ser241Phe). She concurrently experienced recurrence of OS and a new-onset liver tumor at the age of 20 years. Thereafter, microwave ablation was performed for the liver tumor because the Magnetic resonance imaging features suggested that the tumor was a hepatocellular carcinoma. Post-ablation biopsy showed that the tumor cells were spindle-shaped and possessed eosinophilic cytoplasm. Immunohistochemistry revealed that the tumor cells expressed HMB45 and focal alpha-smooth muscle actin. Labeling for S100 protein and cytokeratin-AE1/AE3 yielded negative results. Therefore, a diagnosis of PEComa of the liver was made. Among the ten PEComas reported in patients with Li-Fraumeni syndrome so far, all PEComas except the current case were surgically resected, and no cases of recurrence were documented in the follow-up period. Six of the ten PEComas were located in the liver. We think that the possibility of PEComa should be considered when a liver tumor develops in patients with LFS.
Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disorder caused by a germline pathogenic variant in the MEN1 tumor suppressor gene. Patients with MEN1 have a high risk for primary hyperparath...Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disorder caused by a germline pathogenic variant in the MEN1 tumor suppressor gene. Patients with MEN1 have a high risk for primary hyperparathyroidism (PHPT) with a penetrance of nearly 100%, pituitary adenomas (PitAd) in 40% of patients, and neuroendocrine neoplasms (NEN) of the pancreas (40% of patients), duodenum, lung, and thymus. Increased MEN1-related mortality is mainly related to duodenal-pancreatic and thymic NEN. Management of PHPT differs from that of patients with sporadic disease, as the surgical approach in MEN1-related PHPT includes near-total or total parathyroidectomy because of multigland hyperplasia in most patients and the consequent high risk of recurrence. NEN management also differs from patients with sporadic disease due to multiple synchronous and metasynchronous neoplasms. In addition, the lifelong risk of developing NEN requires special considerations to avoid excessive surgeries and to minimize damage to the patient's function and well-being. This progress report will outline current insights into surveillance and management of the major clinical manifestation of MEN1 syndrome in children and adults with MEN1 diagnosis. In addition, we will discuss MEN1-like clinical presentation with negative MEN1-genetic workup and future clinical and research directions.
Several extra-colonic manifestations, including duodenal polyposis and desmoid tumors, are well-described manifestations in familial adenomatous polyposis (FAP). More recently, an increase in gastric cancer diagnoses has...Several extra-colonic manifestations, including duodenal polyposis and desmoid tumors, are well-described manifestations in familial adenomatous polyposis (FAP). More recently, an increase in gastric cancer diagnoses has been observed in FAP. This case series presents nine patients with FAP who were diagnosed with gastric cancer at our FAP expertise center, of whom eight were diagnosed between 2017 and 2023, while before 2017 the only diagnosis of gastric cancer was in 2001. Among the nine cases of gastric cancer, seven were located in the proximal stomach amidst carpeting fundic gland polyposis and two were located in the distal stomach. Despite ongoing advances in endoscopic technology, all patients were diagnosed during regular endoscopic surveillance, and six of the nine patients died within two years. We aim to raise awareness on gastric cancer risk in FAP patients and stress the urgent need of improved gastric surveillance strategies with timely detection of gastric cancer precursors.
Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome whereby the lifetime risk of developing gastrointestinal and genitourinary cancers rises by to over 50%. It is caused by heterozygous...Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome whereby the lifetime risk of developing gastrointestinal and genitourinary cancers rises by to over 50%. It is caused by heterozygous variants in the DNA mismatch repair genes- MLH1, MSH2, MSH6 and PMS2, with the majority detected in MLH1 and MSH2. Recurrently observed LS-associated variants in apparently unrelated individuals have either arisen de novo in different families due to mutation hotspots or are inherited from a common ancestor (founder) that lived several generations back. Testing for founder variants can facilitate molecular diagnosis of LS more efficiently and cost effectively than screening for all possible variants in the MMR genes. Here, we report a study of the missense variant c.306G > T in the MLH1 gene, the first potential founder variant identified in LS patients of Indian ethnicity. Haplotype analysis consisting of 25 LS carriers with the MLH1 c.306G > T variant and 100 healthy controls confirmed a shared haplotype in cases spanning a 27.8 kb region encompassing the c.306G > T variant (𝝌 = 96.418; p = < 0.0001). Age of variant analysis suggests the variant to have arisen in the population approximately 800 years (95% CI: 670-934 years) ago. Furthermore, it is estimated that c.306G > T variant is likely to be observed in 6.4% of all LS patients of Indian ethnicity. These findings have important implications for genetic counselling and molecular diagnosis of Lynch syndrome.
Retinoblastoma (RB) is the most common intraocular malignancy in children, and patients with family history of retinoblastoma are at high risk of disease. While intensive screening programs have led to earlier diagnosis...Retinoblastoma (RB) is the most common intraocular malignancy in children, and patients with family history of retinoblastoma are at high risk of disease. While intensive screening programs have led to earlier diagnosis and higher rates of globe salvage, visual outcomes have not improved. Handheld optical coherence tomography (HH-OCT) is a non-invasive imaging modality that can be utilized for screening, diagnosis, and monitoring of Familial RB. We present a case of a patient who was found to have bilateral Familial RB with HH-OCT after having a normal fundoscopic exam. This case demonstrates the utility of HH-OCT imaging and suggests that further research is needed to see whether screening guidelines should require OCT imaging during screening.
Nephrotic syndrome is a common clinical presentation of glomerulopathy. A glomerulopathy as a paraneoplastic manifestation caused by underlying malignancy is rare. In patients with a solid tumor, membranous nephropathy i...Nephrotic syndrome is a common clinical presentation of glomerulopathy. A glomerulopathy as a paraneoplastic manifestation caused by underlying malignancy is rare. In patients with a solid tumor, membranous nephropathy is the most frequent paraneoplastic glomerulopathy. We present a case of recurrent paraneoplastic nephrotic syndrome caused by minimal change disease in a patient with Lynch syndrome. Over the years, a decrease in creatinine clearance and nephrotic-range proteinuria repeatedly functioned as a warning signal for underlying malignancies; consecutively, a colon adenocarcinoma, renal cell carcinoma and gastric adenocarcinoma were diagnosed. After treatment of the malignancies the nephrotic syndrome resolved without immunosuppressive therapy. Our patient also developed a primary lung carcinoma thrice, which did not cause an exacerbation of the minimal change disease. To further elucidate the mechanism behind the development of this phenomenon, we performed immunohistochemical analysis for vascular endothelial growth factor (VEGF) on the different tumor specimens. We found a high VEGF expression in the gastro-intestinal tumors, whereas the VEGF expression in the lung tumors was low, suggesting an association between VEGF expression and the development of paraneoplastic minimal change disease. This case report not only underlines the importance of considering a malignancy as a cause for (recurrent) nephrotic syndrome, especially in patients with an increased risk of developing malignancies like Lynch syndrome patients, but also suggests a role for VEGF in the pathogenesis of paraneoplastic minimal change disease.
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors, typically from parathyroid, pancreatic, or anterior pituitary origin. In addition, benign cutaneous soft tissue...Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors, typically from parathyroid, pancreatic, or anterior pituitary origin. In addition, benign cutaneous soft tissue tumors are prevalent in MEN1 patients. Although sarcomas have been reported in MEN1 patients it is unclear if these tumors should be considered as part of the MEN1 syndrome. Here, five patients with a MEN1 syndrome and a sarcoma are described. In all five sarcomas loss of heterozygosity of the MEN1 gene and loss of expression of menin are shown, suggesting that sarcomas may be a phenotypic expression of MEN1 syndrome.
In the Emilia-Romagna region (Northern Italy), the identification and management of women at familial/hereditary risk of breast and ovarian cancer is guided by a well-established regional protocol. Here we report the res...In the Emilia-Romagna region (Northern Italy), the identification and management of women at familial/hereditary risk of breast and ovarian cancer is guided by a well-established regional protocol. Here we report the results of the experience of private supplementation of public healthcare service in offering the possibility to undergo BRCA1/2 testing and/or multigene panel testing (MGPT) within a well-defined pathway to women unfulfilling regional criteria. Out of 177 patients referred to our center who underwent BRCA1/2 testing, 175 tested negative while two (1.1%) resulted carriers of pathogenic variants in BRCA2; 69 patients also underwent MGPT, and in four cases (5.8%) a pathogenic variant were found (two in ATM and one in CHEK2 and RAD51C, respectively). Overall, this private supplementation of territorial public healthcare system has made it possible to confirm the validity of regional criteria for genetic testing access (concordance: 98.9%), but also to identify carriers of pathogenic variants of BRCA1/2 that would have escaped regional protocol, to support the effectiveness of MGPT for the identification of rare cases (not BRCA) at mild/high risk, and to provide reassurance to women who were found to be non-carriers of pathogenic variants, who may benefit from a more accurate assessment of their risk.
Despite its clinical value, cascade genetic testing (CGT) in hereditary cancer syndromes remains underutilized for a number of reasons, including ineffective family communication of genetic risk information. Therefore, a...Despite its clinical value, cascade genetic testing (CGT) in hereditary cancer syndromes remains underutilized for a number of reasons, including ineffective family communication of genetic risk information. Therefore, alternative strategies are being explored to improve CGT uptake rates; one such strategy is direct contact with at-risk relatives by healthcare professionals with proband consent. It is unclear how Italian laws and regulations pertaining to CGT-including the EU General Data Protection Regulation (GDPR)-should be understood and implemented in the context of such alternative strategies. The authors constructed a hypothetical case about CGT, reviewed laws and regulations on informed consent, privacy, and the right not to know, and analyzed how those laws and regulations might apply to different communicative strategies relevant to the case and aimed at supporting CGT. A constitutionally consistent reading of Italian law and of the GDPR, an integral part of the Italian privacy framework, suggests that multiple communicative approaches may be legally permissible in Italy to support the CGT process. This includes direct contact by healthcare professionals with proband consent, provided certain conditions are met. Understanding the effectiveness of such approaches in improving CGT uptake will require further research efforts.
Hereditary cancer predisposition disorders account for up to 10% of all pediatric cancers. Genetic counseling for families of the proband includes risk assessment and recommendations for cascade genetic testing for paren...Hereditary cancer predisposition disorders account for up to 10% of all pediatric cancers. Genetic counseling for families of the proband includes risk assessment and recommendations for cascade genetic testing for parents and siblings, but there is no standardized method for cascade testing in place resulting in variability in how clinics approach cascade genetic testing. We explored the uptake and outcomes associated with a family-based approach to cascade testing, for non-syndromic cancer predisposition disorders, at a pediatric cancer genetics clinic serving an ethnically diverse patient population. A retrospective chart review was conducted to evaluate test uptake in the parents and siblings of 106 pediatric probands. The study included 99 mothers, 97 fathers, 116 full siblings, and 53 half siblings who were recommended testing due to genetic risk. Of these relatives, 156 (43%) had documentation of completed cascade testing within twenty-four months after the proband's result disclosure. Completion of cascade testing varied by the type of family member and degree of relatedness. 41% of mothers (41/99) were tested in comparison to 26% of fathers (26/97) and 70.6% of full siblings (82/116) were tested compared to 13.2% of half siblings (7/53). Statistical analysis using chi-squared tests revealed that siblings were more likely to have completed testing than parents (p < 0.001). Furthermore, amongst parents, mothers were more likely to complete testing than fathers (p = 0.03) and amongst siblings, full siblings were more likely to complete testing than half siblings (< 0.001). The proband's age (p = 0.008), parents' preferred language (p = 0.002), and interpreter use during visit (p = 0.004) were the factors associated with differences in test uptake amongst siblings, whereas the proband's race/ethnicity (p = 0.019) was the only factor associated with differences in test uptake amongst parents. The most common barriers noted in charts for lack of test completion included country of residence, lack of insurance, and loss to follow-up. In conclusion, we found that test uptake differed significantly among relatives of a proband with siblings being more likely to test than parents. We also found differences in the demographic and clinical factors associated with test uptake in parents and siblings. Future studies need to validate these differences and further explore the underlying cause of variation in test uptake among relatives.
Abu Shtaya A, Nathan SN, Kedar I
… +29 more, Friedman E, Half E, Lidzbarsky G, Levi GR, Laish I, Katz L, Bazak L, Peretz LP, Salmon LB, Douiev L, Kalis ML, Schechter M, Barzily-Rokni M, Samra NN, Abu-Freha N, Hagari-Bechar O, Segol O, Mattar S, Barhom SF, Mordechai S, Rafid SS, Shalev SA, Peretz-Yablonski T, Levi Z, Bruchim R, Vinkler C, Bernstein-Molho R, Lieberman S, Goldberg Y
Deciphering the spectrum and founder disease-causing variants (DCVs) in specific populations can shape and facilitate the diagnostic process of Lynch Syndrome (LS). The aim of this report was to comprehensively update on...Deciphering the spectrum and founder disease-causing variants (DCVs) in specific populations can shape and facilitate the diagnostic process of Lynch Syndrome (LS). The aim of this report was to comprehensively update on the genetic landscape of LS in the ethnically diverse Israeli-Jewish population. The cohort included 1080 carriers from 588 families; some from underrepresented, understudied Israeli ethnic groups recruited from 8 genetic institutes and high-risk clinics throughout the country. Variant classification was performed according to the American College of Medical Genetics criteria. A total of 157 DCVs were identified, 12 are reported here for the first time, and 9 reclassified. MSH2 DCVs were identified in 286 families (49%). Most DCVs (125/157, 80%) were noted in one or two families only. Sixteen DCVs, each detected in ≥ 5 families, and accounted for LS in 378/588 (64%) families. Constitutional mismatch repair deficiency (CMMRD) was diagnosed in 7 families. Twenty-five carriers (2.3%) had an additional DCV or risk alleles in another cancer susceptibility gene. In conclusion, MMR gene variant distribution in Israel is diverse. MSH2 is most commonly mutated due to founder DCVs. Though the 16 prevalent LS-associated DCVs were frequently detected in our cohort, none of them is frequently reported in the general population. These data should facilitate variant interpretation, spouse and cascade testing.
Vatsyayan A, Anu RI, Mathur P
… +13 more, Uchil D, Joshi A, Dwivedi A, Sirohi B, Mathew A, Damodaran D, Panda SS, Kolluri S, Ayillath SK, Amalnath D, Shankar G, Pandhare K, Scaria V
As genetic testing becomes increasingly accessible and affordable, the uniform and accurate interpretation of genetic variants becomes essential. The ACMG/AMP joint guidelines provide the basis for systematic and uniform...As genetic testing becomes increasingly accessible and affordable, the uniform and accurate interpretation of genetic variants becomes essential. The ACMG/AMP joint guidelines provide the basis for systematic and uniform interpretation of pathogenicity of genetic variants. However, the application of these in routine clinical interpretation at-scale has largely been limited by the lack of resources providing harmonized data especially at a population-scale. Here we describe BRCAIndica, a resource for BRCA1 and BRCA2 variants conforming to the ACMG & AMP joint guidelines to aid uniform clinical interpretation of genetic tests with a specific focus on variants reported in the Indian population. We collected and harmonized variants from across several resources including population-scale datasets, literature survey and other variant datasets. We then classified them according to the ACMG/AMP guidelines.We have collected a total of 10,490 unique variants, of which 2261 Pathogenic and 43 Likely Pathogenic variants belong to BRCA1 and 2694 Pathogenic and 20 Likely Pathogenic variants to BRCA2 respectively. BRCAIndica can be accessed at:https://clingen.igib.res.in/brcaindica/ . In conclusion, BRCAIndica is a powerful resource that offers researchers and clinicians with ACMG/AMP annotated BRCA variants.
Colorectal cancer (CRC) is a common cancer in Ireland. Of all CRCs, 2-4% are attributable to Lynch Syndrome (LS), the most common CRC predisposition syndrome. LS is caused by constitutional pathogenic variants (PVs) affe...Colorectal cancer (CRC) is a common cancer in Ireland. Of all CRCs, 2-4% are attributable to Lynch Syndrome (LS), the most common CRC predisposition syndrome. LS is caused by constitutional pathogenic variants (PVs) affecting mismatch repair (MMR) genes with resultant MMR protein deficiency (dMMR). Screening of all CRCs with MMR immunohistochemistry (IHC) testing is advocated to increase the detection of LS. However, successful implementation requires appropriate downstream management. In Ireland the traditional pathway involves referral to cancer genetics services to assess eligibility for genetic testing. Cancer genetics services in Ireland face many challenges in providing uniform access to timely healthcare with current wait times for assessment in excess of 1 year. An increasingly adopted pathway is that of mainstreaming, whereby genetic testing is managed locally by a multidisciplinary team member. Our institution therefore implemented an Advanced Nurse Practitioner (ANP)-led service with responsibility for the LS Diagnostic Pathway and mainstream genetic testing. Data was extracted from a prospectively maintained database of all newly diagnosed CRC patients discussed at our institutions CRC multidisciplinary meeting (MDM) between January 1st, 2023, and May 31st, 2024. MMR IHC testing was performed in 97.9% of the 385 patients diagnosed with CRC. The median time from histological confirmation of CRC to the availability of the MMR IHC report was 6 days. All 51 patients (100%) who required sequential tumor testing underwent BRAF V600 ± MLH1 promoter methylation testing. Additionally, 100% of the 14 patients eligible for mainstream genetic testing were referred to the ANP-led genetics service. The median time from the initial MDM discussion to the initiation of genetic testing was 69 days, while the median time from testing to the availability of results was 19 days. Patients received their results within a median of 21 days. MMR IHC testing increases the detection of LS through identification of dMMR tumours. Successful downstream delivery of clinical services, however, requires appropriate subsequent management, in a resource-limited environment. Our institutional experience demonstrates the feasibility, efficiency, and effectiveness of an ANP-led mainstreaming model of care for hereditary colorectal cancer.
Risk reduction salpingo-oophorectomy (RRSO) is usually performed in women with hereditary breast and ovarian cancer (HBOC) syndrome for BRCA1 and BRCA2 gene mutation carriers, resulting in surgical menopause, which is mo...Risk reduction salpingo-oophorectomy (RRSO) is usually performed in women with hereditary breast and ovarian cancer (HBOC) syndrome for BRCA1 and BRCA2 gene mutation carriers, resulting in surgical menopause, which is more associated with a high risk of cardiovascular and metabolic disease than in premenopausal and natural menopausal women. This study assessed the prevalence of cardiovascular and metabolic outcomes in women who underwent salpingo-oophorectomy as a preventive measure against HBOC. This meta-analysis assessed prevalence rates for four metabolic/cardiovascular conditions: myocardial infarction, hypertension, hypercholesterolemia, and type 2 diabetes mellitus. DerSimonian and Laird random-effects models were applied to all analyses, with 95% confidence interval (CI). Heterogeneity was assessed with I². We used OpenMeta Analyst software for statistical analysis. A total of five retrospective studies and one observational study involving 1,320 patients were included. The average body mass index (BMI) was 25.97 kg/m2 and the average waist circumference was 87.94 cm. The analysis across a mean 4.94-year follow-up revealed prevalence rates for acute myocardial infarction of 1.5% (95% CI 0.3-2.7; P = 0.077; I²=56.25%), hypertension of 28% (95% CI 6.9-49.1; P < 0.001; I = 98.42%), hypercholesterolemia of 27.2% (95% CI 6.8-47.6; P < 0.001; I²=98.67%), and type 2 diabetes mellitus of 3.3% (95% CI 1.1-5.5; P < 0.001; I²=82.44%). Our findings suggest that there is no marked increase in cardiovascular risk among women with HBOC undergoing RRSO.