Nuclear Pedigree Criteria for the Identification of Individuals Suspected to be at Risk of an Inherited Predisposition to Renal Cancer

Renal clear cell carcinomas represent about 3% of all visceral cancers and account for approximately 85% of renal cancers in adults. Environmental and genetic factors are involved in the development of renal cancer. Although to date there are 19 hereditary syndromes described in which renal cell cancer may occur, only four syndromes with an unequivocal genetic predisposition to renal cell carcinoma have been identified: VHL syndrome (mutations in the VHL gene), hereditary clear cell carcinoma (translocations t(3:8), t(2:3)), hereditary papillary carcinoma (mutations in the MET protooncogene) and tuberous sclerosis (mutations in the TSC1 and TSC2 genes). Little is known genetically about the other forms of familial renal cell cancer. Since there is a growing awareness about the necessity of early intervention, clinical criteria have been developed that aid in the identification of hereditary forms of renal cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be ascertained for risk assessment and/or kidney tumour screening. The results reveal that inclusion features described herein, such as (a) renal clear cell cancer diagnosed before 55 years of age, and (b) renal clear cell cancer and gastric cancer or lung cancer among first degree relatives, are useful in identifying suspected hereditary clear cell renal cancer patients

Badania ultrasonograficzne tarczycy u pacjentek obciążonych występowaniem nowotworów rodzinnych

Background: Detection of new gene mutations, which increase the risk of neoplasm (e.g. breast and thyroid gland) improves the examinations that can help in early diagnosis and quick treatment. The aim of this study was to assess the frequency of asymptomatic focal lesions in ultrasonographic examinations of women at confirmed risk of family neoplasm aggregation. Material/Methods: A total of 445 women aged 25-60 years were examined in 2004-2005. 278 patients descended from families with higher frequency of confirmed risk of familial neoplasm (I group), 167 belonged to the control group. Ultrasonographic examinations of the breast and thyroid gland were performed in all women. Patients were divided into selected groups depending on the kind of changes. Results: In the analyzed material asymptomatic focal changes in the thyroid gland were found in 46, 5% of the first group and 61,6% of the control group. The solid-cystic lesions in this material were ascertained in 36% of the first group and 51% of the second group. Conclusions: A large frequency (almost 50%) of the asymptomatic focal changes in thyroid glands were found. Detections of lesions were similar in both groups: the confirmed risk of familial neoplasm group and the control group. On the basis of these findings we can conclude, that it is reasonable to perform screening examinations of thyroid glands in connection with breast's diagnostics

CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland

Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome characterized by a high risk of diffuse stomach cancer and lobular breast cancer. HDGC is caused by germline mutations in the CDH1 gene encoding the E-cadherin which is a member of the transmembrane glycoprotein family responsible for calcium-dependent, cell-to-cell adhesion and plays a fundamental role in the maintenance of cell differentiation and the normal architecture of epithelial tissues. Mutations in the CDH1 gene are detected in 30–46% of families that fulfil strong clinical criteria for HDGC and in about 11% of families fulfilling the modified criteria. In the present study, we investigated germline mutations in the CDH1 gene in Polish patients with HDGC. The entire coding sequence of CDH1 gene was analyzed by sequencing in 86 Polish cancer patients from families fulfilling the modified criteria of HDGC. We found several silent mutations including one common variant (c.2076T>C) present in 56 patients, and three rare variants (c.2253C>T, c.1896C>T, c.2634C>T) detected in 2 patients. In addition, we found four rare sequence variants of unknown significance localized in introns. We did not detect any deleterious mutations of the CDH1 gene. CDH1 gene mutations are not present in Polish families with HDGC defined by the modified clinical criteria. Further studies of families with HDGC matching the restrictive criteria for HDGC are needed

-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms

International audiencePolymorphisms in genes involved in DNA repair, steroid hormone biosynthesis/metabolism/signaling, folate metabolism as well as cell growth are prime candidates for possible associations with breast and ovarian cancer risk in women with an inherited predisposition. We investigated 29 polymorphisms in 20 genes encoding key proteins of the above four biological pathways for their breast and ovarian cancer risk modifying effect in Polish women harboring founder mutations. Of the analyzed genes, , , , and participate in DNA repair, in cell cycle check point control, , , , , , , and in steroid hormone biosynthesis/metabolism/signaling, in folate metabolism and , , , and affect cell growth. Using validated methods, we genotyped 319 breast cancer cases, 146 ovarian cancer cases and 290 unaffected controls, all of whom harbored one of three causative mutations in . Our results revealed no association of any of the investigated polymorphisms with -associated breast or ovarian cancer risk. Thus, it appears that these polymorphisms do not influence disease risk in Polish women carrying one of the three common founder mutations