Contribution to colonic polyposis of recently proposed predisposing genes and assessment of the prevalence of NTHL1 ‐ and MSH3 ‐associated polyposes

2019 ◽  
Vol 40 (11) ◽  
pp. 1910-1923 ◽  
Author(s):  
Mariona Terradas ◽  
Pau M. Munoz‐Torres ◽  
Sami Belhadj ◽  
Gemma Aiza ◽  
Matilde Navarro ◽  
...  
Keyword(s):  
Predisposing Genes ◽  
Colonic Polyposis

scholarly journals Investigation of monogenic causes of familial breast cancer: data from the BEACCON case-control study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Li ◽  
Belle W. X. Lim ◽  
Ella R. Thompson ◽  
Simone McInerny ◽  
Magnus Zethoven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Candidate Genes ◽  
Familial Aggregation ◽  
Loss Of Function ◽  
Cancer Data ◽  
Pathogenic Variants ◽  
New Genes ◽  
Predisposing Genes ◽  
Predisposition Genes

AbstractBreast cancer (BC) has a significant heritable component but the genetic contribution remains unresolved in the majority of high-risk BC families. This study aims to investigate the monogenic causes underlying the familial aggregation of BC beyond BRCA1 and BRCA2, including the identification of new predisposing genes. A total of 11,511 non-BRCA familial BC cases and population-matched cancer-free female controls in the BEACCON study were investigated in two sequencing phases: 1303 candidate genes in up to 3892 cases and controls, followed by validation of 145 shortlisted genes in an additional 7619 subjects. The coding regions and exon–intron boundaries of all candidate genes and 14 previously proposed BC genes were sequenced using custom designed sequencing panels. Pedigree and pathology data were analysed to identify genotype-specific associations. The contribution of ATM, PALB2 and CHEK2 to BC predisposition was confirmed, but not RAD50 and NBN. An overall excess of loss-of-function (LoF) (OR 1.27, p = 9.05 × 10−9) and missense (OR 1.27, p = 3.96 × 10−73) variants was observed in the cases for the 145 candidate genes. Leading candidates harbored LoF variants with observed ORs of 2–4 and individually accounted for no more than 0.79% of the cases. New genes proposed by this study include NTHL1, WRN, PARP2, CTH and CDK9. The new candidate BC predisposition genes identified in BEACCON indicate that much of the remaining genetic causes of high-risk BC families are due to genes in which pathogenic variants are both very rare and convey only low to moderate risk.

scholarly journals Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Author(s):  
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Early Onset ◽  
Low Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Pathogenic Variants ◽  
Predisposing Genes ◽  
The Mean ◽  
Early Onset Colorectal Cancer

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.

Colonic polyposis due to Schistosoma intercalatum

2010 ◽  
Vol 104 (6) ◽  
pp. 443-445 ◽  
Author(s):  
Azucena Rodríguez-Guardado ◽  
Rosa Miquel ◽  
Francisco Pérez ◽  
Manuel Fresno ◽  
Manuel Corachán
Keyword(s):  
Colonic Polyposis ◽  
Schistosoma Intercalatum

Metastases of a gastric adenocarcinoma presenting as colonic polyposis

1991 ◽  
Vol 34 (7) ◽  
pp. 622-623 ◽  
Author(s):  
Patrice Metayer ◽  
Michel Antonietti ◽  
Mohammed Oumrani ◽  
Jacques Hemet ◽  
Françoise Lemoine ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Colonic Polyposis

Challenging colonic polyposis pedigrees: differential diagnosis, surveillance, and management concerns

2004 ◽  
Vol 148 (2) ◽  
pp. 104-117 ◽  
Author(s):  
Henry T Lynch ◽  
Susan T Tinley ◽  
Trudy G Shaw ◽  
Jane F Lynch ◽  
James R Howe ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Colonic Polyposis

Effects of Breastfeeding and Formula Feeding on the Metabolic Factors and the Expression Level of Obesity and Diabetes-Predisposing Genes in Healthy Infants

2021 ◽  
Author(s):  
Sahar Cheshmeh ◽  
Amir Saber ◽  
Seyed Mostafa Nachvak ◽  
Niloofar Hojati ◽  
Negin Elahi ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Formula Feeding ◽  
Lipoprotein Cholesterol ◽  
Expression Level ◽  
Metabolic Factors ◽  
Anthropometric Indices ◽  
Ppar Γ ◽  
Obesity And Diabetes ◽  
Healthy Infants ◽  
Predisposing Genes

Abstract Background: Diabetes mellitus (DM) and obesity are prevalent disorders diagnosed by glucose metabolism problems and excess weight gain. Breastfeeding is the best feeding way for infants until six months and due to its nutritional properties, has desirable effects on diabetes and obesity. This study aimed to investigate the effects of breastfeeding, formula feeding, and formula-plus breastfeeding (mix-feeding) on the anthropometric indices, metabolic factors, and the expression level of obesity and diabetes-predisposing genes of healthy infants. Methods: A total of 150 healthy infants were enrolled in this cross-sectional study. All infants (aged 24 months) based on the type of their feeding were divided into three groups, breastfeeding, formula feeding, and mix-feeding. The anthropometric indices, glycemic indexes, lipid profile, and the expression level of acetyl-coenzyme A carboxylase beta (ACACB), brain-derived neurotrophic factor (BDNF), liver X receptor α (LXR-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and phosphatase and tensin homolog (PTEN) genes were assessed for all infants using reverse transcription-polymerase chain reaction (RT-PCR) method. Results: The anthropometric indices including weight, height, and head circumference, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were lower in the breastfeeding infants in comparison to other groups. As well, the expression level of the ACACB gene was significantly downregulated in breastfeeding infants, while the PPAR-γ gene was significantly upregulated, but the expression level of LXR- α, PTEN and BDNF didn’t show a significant difference between groups.Conclusions: Breastfeeding in comparison with formula feeding possessed desirable effects on anthropometric indices, metabolic factors, and diabetes-predisposing genes.

scholarly journals Does multilocus inherited neoplasia alleles syndrome have severe clinical expression?

2018 ◽  
Vol 56 (8) ◽  
pp. 521-525 ◽  
Author(s):  
Agostina Stradella ◽  
Jesús del Valle ◽  
Paula Rofes ◽  
Lídia Feliubadaló ◽  
Èlia Grau Garces ◽  
...  
Keyword(s):  
Hereditary Cancer ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Cancer Genes ◽  
Pathogenic Mutations ◽  
Predisposing Genes ◽  
Definition Of ◽  
Gene Panels

ImportanceGenetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations.ObjectiveTo determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel.Patients and methodsA cohort of 1023 unrelated patients with suspicion of hereditary cancer was screened using a validated panel including up to 135 genes associated with hereditary cancer and phakomatoses.ResultsThirteen (1.37%) patients harbouring two pathogenic mutations in dominant cancer-predisposing genes were identified, representing 5.7% (13/226) of patients with pathogenic mutations. Most (10/13) of these cases presented clinical manifestations associated with only one of the mutations identified. One case showed mutations in MEN1 and MLH1 and developed tumours associated with both cancer syndromes. Interestingly, three of the double mutants had a young age of onset or severe breast cancer phenotype and carried mutations in moderate to low-risk DNA damage repair-associated genes; two of them presented biallelic inactivation of CHEK2. We included these two patients for the sake of their clinical interest although we are aware that they do not exactly fulfil the definition of MINAS since both mutations are in the same gene.Conclusions and relevanceGenetic analysis of a broad cancer gene panel identified the largest series of patients with MINAS described in a single study. Overall, our data do not support the existence of more severe manifestations in double mutants at the time of diagnosis although they do confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA repair cancer-predisposing genes.

scholarly journals 15 YEARS OF PARAGANGLIOMA: The association of pituitary adenomas and phaeochromocytomas or paragangliomas

2015 ◽  
Vol 22 (4) ◽  
pp. T105-T122 ◽  
Author(s):  
Samuel M O'Toole ◽  
Judit Dénes ◽  
Mercedes Robledo ◽  
Constantine A Stratakis ◽  
Márta Korbonits
Keyword(s):  
Succinate Dehydrogenase ◽  
Molecular Genetics ◽  
Pituitary Adenomas ◽  
Rare Event ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Endocrine Tumours ◽  
Pituitary Tumorigenesis ◽  
Predisposing Genes

The combination of pituitary adenomas (PA) and phaeochromocytomas (phaeo) or paragangliomas (PGL) is a rare event. Although these endocrine tumours may occur together by coincidence, there is mounting evidence that, in at least some cases, classical phaeo/PGL-predisposing genes may also play a role in pituitary tumorigenesis. A new condition that we termed ‘3Pas’ for the association of PA with phaeo and/or PGL was recently described in patients with succinate dehydrogenase mutations and PAs. It should also be noted that the classical tumour suppressor gene,MEN1that is the archetype of the PA-predisposing genes, is also rarely associated with phaeos in both mice and humans with MEN1 defects. In this report, we review the data leading to the discovery of 3PAs, other associations linking PAs with phaeos and/or PGLs, and the corresponding clinical and molecular genetics.

scholarly journals Frequent EPAS1/HIF2α exons 9 and 12 mutations in non-familial pheochromocytoma

2014 ◽  
Vol 21 (3) ◽  
pp. 495-504 ◽  
Author(s):  
Jenny Welander ◽  
Adam Andreasson ◽  
Michael Brauckhoff ◽  
Martin Bäckdahl ◽  
Catharina Larsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Gene Expression Pattern ◽  
Exon 2 ◽  
Dna And Rna ◽  
Familial Pheochromocytoma ◽  
Predisposing Genes ◽  
Adrenal Pheochromocytoma ◽  
New Gene ◽  
Sporadic Pheochromocytoma

Pheochromocytomas are neuroendocrine tumors arising from the adrenal medulla. While heritable mutations are frequently described, less is known about the genetics of sporadic pheochromocytoma. Mutations in genes involved in the cellular hypoxia response have been identified in tumors, and recentlyEPAS1, encoding HIF2α, has been revealed to be a new gene involved in the pathogenesis of pheochromocytoma and abdominal paraganglioma. The aim of this study was to further characterizeEPAS1alterations in non-familial pheochromocytomas. Tumor DNA from 42 adrenal pheochromocytoma cases with apparently sporadic presentation, without known hereditary mutations in predisposing genes, were analyzed for mutations inEPAS1by sequencing of exons 9 and 12, which contain the two hydroxylation sites involved in HIF2α degradation, and also exon 2. In addition, the copy number at theEPAS1locus as well as transcriptome-wide gene expression were studied by DNA and RNA microarray analyses, respectively. We identified six missenseEPAS1mutations, three in exon 9 and three in exon 12, in five of 42 pheochromocytomas (12%). The mutations were both somatic and constitutional, and had no overlap in 11 cases (26%) with somatic mutations inNF1orRET. One sample had two differentEPAS1mutations, shown by cloning to occur incis, possibly indicating a novel mechanism of HIF2α stabilization through inactivation of both hydroxylation sites. One of the tumors with anEPAS1mutation also had a gain in DNA copy number at theEPAS1locus. AllEPAS1-mutated tumors displayed a pseudo-hypoxic gene expression pattern, indicating an oncogenic role of the identified mutations.

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