Hereditary Cancer in Clinical Practice 

About: Hereditary Cancer in Clinical Practice is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Cancer & Breast cancer. It has an ISSN identifier of 1731-2302. It is also open access. Over the lifetime, 609 publications have been published receiving 5952 citations.

Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients

Abstract: Cancer risk and Lhermitte-Duclos disease (LDD) risk estimates for Cowden syndrome (CS) are broad and based on a small number of patients. Risk estimates are vital to the development of diagnostic criteria, genetic counseling, and cancer surveillance. To further elaborate and estimate the risks associated with CS, a large cohort of patients was evaluated. CS patients were identified from the medical literature and the Mayo Clinic's records. All patients met accepted diagnostic criteria for CS. A total of 211 CS patients (age 44 ± 16 years, 64% female, 46% PTEN mutation) were included (published literature 90% and Mayo Clinic series 10%). The cumulative lifetime (age 70 years) risks were 89% for any cancer diagnosis (95% confidence interval (CI) = 80%,95%), breast cancer [female] 81% (CI = 66%,90%), LDD 32% (CI = 19%,49%), thyroid cancer 21% (CI = 14%,29%), endometrial cancer 19% (CI = 10%,32%), and renal cancer 15% (CI = 6%,32%). A previously unreported increased lifetime risk for colorectal cancer was identified (16%, CI = 8%,24%). Male CS patients had fewer cancers diagnosed than female patients and often had cancers not classically associated with CS. Seven percent of breast and thyroid cancers occurred in patients who were younger than the recommended age to commence radiographic cancer screening. There was a trend for patients with a family history of CS and PTEN mutations to have a lower cancer risk than those without. This study confirms CS patients are at increased risk for cancer and quantitative data is provided to guide clinical care. Based on a different tumor spectrum, separate male and female clinical CS diagnostic criteria may be indicated.

The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers

Abstract: The association of germline mutations in the breast cancer susceptibility gene 1 (BRCA1) and the breast cancer susceptibility gene 2 (BRCA2) with the development of breast and ovarian cancers have been widely researched and recognised. It is known that these genes function at multiple sites in the body. Research has subsequently evolved into the connection of BRCA1/2 with cancers at other sites within the body. This review examines the association of BRCA1/2 germline gene mutations with prostate, pancreatic and stomach cancers. An extensive literature search revealed conflicting findings regarding the association of BRCA1/2 gene mutations with these cancers. Most studies suggest that there is an association between BRCA1/2 mutations and carcinoma of the prostate, pancreas and stomach, but some reports propose that such a correlation may be due to factors other than possessing a mutated BRCA1/2 gene, and other associations may be revealed as further epidemiological information becomes available. The review concludes that as more knowledge arises about the mechanisms of BRCA1/2 gene mutations, it should pave the way for future screening programmes to be applied effectively.

Germline deletions in the EPCAM gene as a cause of Lynch syndrome – literature review

Abstract: Lynch syndrome (clinically referred to as HNPCC – Hereditary Non-Polyposis Colorectal Cancer) is a frequent, autosomal, dominantly-inherited cancer predisposition syndrome caused by various germline alterations that affect DNA mismatch repair genes, mainly MLH1 and MSH2 Patients inheriting this predisposition are susceptible to colorectal, endometrial and other extracolonic tumors It has recently been shown that germline deletions of the last few exons of the EPCAM gene are involved in the etiology of Lynch syndrome Such constitutional mutations lead to subsequent epigenetic silencing of a neighbouring gene, here, MSH2, causing Lynch syndrome Thus, deletions of the last few exons of EPCAM constitute a distinct class of mutations associated with HNPCC Worldwide, several investigators have reported families with EPCAM 3’end deletions The risk of colorectal cancer in carriers of EPCAM deletions is comparable to situations when patients are MSH2 mutation carriers, and is associated with high expression levels of EPCAM in colorectal cancer stem cells A lower risk of endometrial cancer was also reported Until now the standard diagnostic tests for Lynch syndrome have contained analyses such as immunohistochemistry and tests for microsatellite instability of mismatch repair genes The identification of EPCAM deletions or larger EPCAM-MSH2 deletions should be included in routine mutation screening, as this has implications for cancer predisposition

Familial Adenomatous Polyposis: Experience from a Study of 1164 Unrelated German Polyposis Patients

Abstract: The autosomal-dominant precancerous condition familial adenomatous polyposis (FAP) is caused by germline mutations in the tumour suppressor gene APC. Consistent correlations between the site of mutations in the gene and clinical phenotype have been published for different patient groups. We report our experiences of APC mutation analysis and genotype-phenotype correlations in 1166 unrelated polyposis families and discuss our results in the light of literature data. We show that the mutation detection rates largely depend on the family history and clinical course of the disease. We present a list of 315 different point mutations and 37 large deletions detected in 634 of the 1166 index patients. Our results confirm previously published genotype-phenotype correlations with respect to the colorectal phenotype and extracolonic manifestations. However, 'exceptions to the rule' are also observed, and possible explanations for this are discussed. The discovery of autosomal-recessive MUTYH-associated polyposis (MAP) as a differential diagnosis to FAP implies that some results have to be reinterpreted and surveillance guidelines in the families have to be reevaluated.

Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients

Abstract: Background Neoadjuvant chemotherapy is administered to control disease, make surgical resection possible and increase the possibility of breast tissue conservation. A further advantage of neoadjuvant therapy is that it helps to assess chemo-sensitivity to a particular agent. Induction of a pathological complete response (pCR) is one of the primary goals of neoadjuvant therapy in order to achieve a better disease-free and overall survival. Experimental data suggest that BRCA1 related breast cancer may have increased sensitivity to platinum-based chemotherapy, but clinical data are limited. The aim of this study was to evaluate the frequency of complete pathologic response after neo-adjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation.