Cowden Syndrome
Dongyou Liu in Handbook of Tumor Syndromes, 2020
Patients with Cowden syndrome are at increased risk of developing cancers of the breast, thyroid, uterus (endometrial), kidney, and colorectum. Benign breast conditions (e.g., ductal hyperplasia, intraductal papillomatosis, adenosis, lobular atrophy, fibroadenomas, and fibrocystic changes) and thyroid abnormalities (e.g., noncancerous adenomas, goiter, and cysts) may occur in up to 75% and over 50% of patients, respectively. Females with a PTEN pathogenic variant have an 85% lifetime risk for breast cancer, and penetrance of 50% by 50 years of age. Patients also show a 35% lifetime risk for epithelial thyroid cancer, with a median age of onset at 37 years; however, no medullary thyroid carcinoma is observed. Further, patients have a 28% lifetime risk for endometrial cancer, with an onset age between the late 30s and early 40s. Over 90% of individuals with a PTEN pathogenic variant develop polyps (ranging from ganglioneuromatous polyps, hamartomatous polyps, and juvenile polyps to adenomatous polyps) and have a 9% lifetime risk for colorectal cancer, with an onset age in the late 30s. Patients also have a 35% lifetime risk for renal cell carcinoma (predominantly of papillary histology), with an onset age of the 40s [18–22].
Pediatric Central Nervous System Tumors as Phenotypic Manifestation of Cancer Predisposition Syndromes
David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack in Brain and Spinal Tumors of Childhood, 2020
Dysplastic cerebellar gangliocytoma is a benign cerebellar neoplasm typically arising in young adults, rarely in children.74 This exquisitely rare pediatric neoplasm is usually seen in patients with Cowden syndrome or multiple hamartoma syndrome. Cowden syndrome is an autosomal-dominant inherited condition characterized by the presence of multiple papillomatous lesions, and multiple hamartomas which predispose affected patients to a high risk of developing follicular thyroid, breast, and endometrial cancers. Macrocephaly is considered potential clinical stigmata of Cowden syndrome. It has been linked to a germline mutation of the PTEN gene located at the 10q23 locus. The PTEN gene product is a negative regulator in the phosphatidylinositol-3-kinase protein kinase (PI3K-AKT) which targets the rapamycin (mTOR) signaling pathway.74,75
Breast cancer
Anju Sahdev, Sarah J. Vinnicombe in Husband & Reznek's Imaging in Oncology, 2020
Women with two affected first-degree relatives have a four- to fivefold increased relative risk (7). High-risk genetic mutations, e.g. the autosomal dominant BRCA1 and 2 mutations, account for 5%–10% of all breast cancer diagnoses (8). These mutations impart a lifetime risk of up to 70% (9). BRCA genes are involved in homologous repair of double-stranded DNA breaks, hence the carcinogenicity of mutations. The general prevalence of these mutations is low (approximately 0.7% for BRCA1), but penetrance is high. A mutation in the TP53 tumour-suppressor gene on the short arm of chromosome 17 causes Li-Fraumeni syndrome, conferring a lifetime risk for breast cancer of nearly 100% (10). Mutations in the PTEN tumour-suppressor gene result in Cowden syndrome, this rare mutation imparting a lifetime risk up to 85% (11). If a family history suggests a high-risk mutation (multiple family members affected at a young age, bilateral breast cancer at a young age, ‘triple-negative’ breast cancer (TNBC) under the age of 50 (not expressing oestrogen, progesterone receptors or overexpressing HER2), counselling and genetic testing is recommended (12). Of more importance in terms of population-attributable risk are the far commoner low-penetrance alleles. Genome-wide association studies have demonstrated single nucleotide polymorphisms (SNPs) at over 100 loci. The risk conferred by each SNP is small, but their effects are additive, and a polygenic risk score (PRS) derived from an 18- or 77-panel PRS improves risk stratification when added to family-history models (13).
Sociodemographic predictors of endometrial cancer mortality in South Africa (1997 to 2015): a case-control study
Published in Journal of Obstetrics and Gynaecology, 2022
Adebukola I. Ewuola, Gbenga Olorunfemi, Julian Q. Mthombeni
The pathophysiology of endometrial cancer is multi-factorial. However, the key aetiology is chronic excessive unopposed action of oestrogen on the uterine endometrium. Common risk factors of endometrial cancer include obesity, early menarche, late menopause, advanced age, and some genetic predisposition such as Lynch syndrome and Cowden syndrome (Kumar et al. 2014). While most studies have focussed on the risk factor for the incidence, few have evaluated the risk factor for the mortality of endometrial cancer (Brüggmann et al. 2020). Although, South Africa currently has national cancer control programs for breast (National Department of Health 2017a) and cervical cancer (National Department of Health, 2017 b), there is no national cancer control guideline for endometrial cancer. This study therefore evaluates the socio-demographic risk factors of mortality from endometrial cancer as compared to death from other cancers among South African women from 1997 to 2015. The result from this study will contribute to evidence for designing an endometrial cancer control program in the country.
Role of immune checkpoint inhibitors in the treatment of colorectal cancer: focus on nivolumab
Published in Expert Opinion on Biological Therapy, 2019
Alexandre A. Jácome, Cathy Eng
Germline mutations in one of the several MMR genes occur in Lynch syndrome, also called hereditary nonpolyposis CRC (HNPCC) [65]. The other inherited patterns of CRC are not involved with MMR genes. These are involved with APC gene, and form the polyposis syndromes: familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and the hamartomatous polyposis syndromes (Peutz-Jeghers, juvenile polyposis, Cowden syndrome) [66]. A less understood pattern is familial CRC, estimated to be present in 25% of patients [67]. These patients have family history of CRC, but they do not have an inherited identified genetic mutation, and do not have a pattern consistent with one of the inherited syndromes.
Related Knowledge Centers
- Hamartoma
- Palmoplantar Keratoderma
- Trichilemmoma
- Tumor Suppressor Gene
- Papilloma
- Macrocephaly
- Dominance
- Pten
- Mtor
- Cutaneous Squamous-Cell Carcinoma