After further stratification of the cancer group into different clinical-pathologic parameters, there were significant associations in the sex and LN involvement groups in MK gene; alcohol consumption group in p16 gene; age and cell differentiation groups in p21 gene; age and tumour location groups in p53 gene; but we fail to find any significant association with IL-4 gene polymorphisms.
Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases.
We identified deletions overlapping two known cancer susceptibility genes, (BRCA1 and BLM), and a duplication overlapping SMARCB1, associated with risk.
This study examined whether participants who learned research results related to a germline CDKN2A variant known to be associated with increased risk of pancreatic cancer and malignant melanoma would pursue confirmatory testing and cancer screening, share the genetic information with health care providers and family, and change risk perceptions.
The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline loss-of-function mutations in either BRCA1 or BRCA2.
The proto-oncogene KRAS belongs among the most frequently mutated genes in all types of cancer and is also very important oncogene related to colorectal tumors.
Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy.
The authors conducted a retrospective review of records for 554 women who had undergone testing at The University of Texas M. D. Anderson Cancer Center between 2000 and 2006 for deleterious BRCA1 and BRCA2 gene mutations.
The importance of the CDK4 locus in human cancer first became evident following the identification of a germ line CDK4-Arg24Cys (R24C) mutation, which abolishes the ability of CDK4 to bind to p16(INK4a).
Our approach integrates four interdependent epidemiologic parameters: (1) the probability of developing breast cancer, (2) the proportion of breast cancer cases with a BRCA1 or BRCA2 mutation, (3) the proportion of women that carries a mutation, and (4) the proportion of women with a mutation that develops cancer.
Better clinical characterization of this subtype might allow application of targeted therapy for CCA patients with germline or somatic mutations in <i>BRCA1/2</i> genes, especially due to previously reported success of such therapies in other BRCA-associated malignancies.
Women identified as BRCA1 and BRCA2 mutation carriers are advised to manage their cancer risk through intensive screening programs and/or by undergoing risk-reducing surgery.
The obtained results allow us to conclude: (i) survival times of 500 C/G carriers vs. cumulating proportion surviving was not statistically significant; (ii) CDKN2a polymorphism 500 C/G correlated with Ala148Thr; (iii) no correlation was observed between the 500 C/G polymorphism and age of diagnosis, localization of primary melanoma and survival time; (iv) we did not find correlation between 500 C/G and type of cancer in the family; (v) changes in the CDKN2a gene were not found in patients with second cancer.
Genotyping of BRCA1 and BRCA2 in the Italian family revealed the presence of two significant polymorphisms: the cancer-associated c.2612C>T SNP in BRCA1, and the c.-26G>A SNP in the BRCA2 gene, acting as an ovarian cancer risk modifier in carriers of deleterious BRCA1 mutations.
Women, at least 21 years of age, who had undergone cancer genetic counseling with (1) at least a 10% predicted likelihood of carrying a BRCA1/2 mutation or (2) a documented BRCA1/2 mutation.
The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management.