Genetic variants in <Emphasis Type="Italic">MMP9</Emphasis> and <Emphasis Type="Italic">TCF2</Emphasis> contribute to susceptibility to lung cancer

Objective|  

The Wnt signaling pathway is crucial for pulmonary development and differentiation; dysregulation of the Wnt signaling pathway may impair lung function. Indeed, single nucleotide polymorphisms (SNPs) of Wnt pathway-related genes have been suggested as risk factors for certain types of cancers. In this study, we aimed to evaluate the influence of SNPs in Wnt-related genes (TCF2, MMP9) on susceptibility to lung cancer.     

Polymorphisms of the <Emphasis Type="Italic">XRCC1</Emphasis>, <Emphasis Type="Italic">XRCC3</Emphasis>, &; <Emphasis Type="Italic">XPD</Emphasis>genes,and colorectal cancer risk: a case-control study in Taiwan

Background  

Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer.     

Variants in estrogen-biosynthesis genes <Emphasis Type="Italic">CYP17</Emphasis> and <Emphasis Type="Italic">CYP19</Emphasis> and breast cancer risk: a family-based genetic association study

Background  

Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T→C promoter polymorphism) and CYP19 (TTTA repeat polymorphism).     

The siRNA targeted to <Emphasis Type="Italic">mdr1b</Emphasis> and <Emphasis Type="Italic">mdr1a</Emphasis> mRNAs <Emphasis Type="Italic">in vivo</Emphasis>sensitizes murine lymphosarcoma to chemotherapy

Background  

One of the main obstacles for successful cancer polychemotherapy is multiple drug resistance phenotype (MDR) acquired by tumor cells. Currently, RNA interference represents a perspective strategy to overcome MDR via silencing the genes involved in development of this deleterious phenotype (genes of ABC transporters, antiapoptotic genes, etc.).     

<Emphasis Type="Italic">In vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> anticancer properties of a <Emphasis Type="Italic">Calcarea carbonica</Emphasis> derivative complex (M8) treatment in a murine melanoma model

Background  

Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from Calcarea carbonica (M8) stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells in vitro.     

Genetic variants of <Emphasis Type="Italic">CYP3A5</Emphasis>, <Emphasis Type="Italic">CYP2D6</Emphasis>, <Emphasis Type="Italic">SULT1A1</Emphasis>, <Emphasis Type="Italic">UGT2B15</Emphasis> and tamoxifen response in postmenopausal patients with breast cancer

Introduction  

Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer. Even if most patients benefit from tamoxifen, many breast tumours either fail to respond or become resistant. Because tamoxifen is extensively metabolised by polymorphic enzymes, one proposed mechanism underlying the resistance is altered metabolism. In the present study we investigated the prognostic and/or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 (*3), CYP2D6 (*4), sulphotransferase 1A1 (SULT1A1; *2) and UDP-glucuronosyltransferase 2B15 (UGT2B15; *2) in tamoxifen-treated patients with breast cancer.     

A comprehensive analysis of common genetic variation in <Emphasis Type="Italic">MUC1</Emphasis>, <Emphasis Type="Italic">MUC5AC</Emphasis>, <Emphasis Type="Italic">MUC6</Emphasis> genes and risk of stomach cancer

Objective  

MUC1, MUC5AC, and MUC6 are main constituents of the mucus barrier in the stomach, which protects the underlying epithelium from acid, proteases, mechanical trauma, and pathogenic microorganisms. Accumulating evidence implicates potential roles of MUC1, MUC5AC, and MUC6 genetic variation in the development of stomach cancer.     

<Emphasis Type="Italic">ABI3</Emphasis> ectopic expression reduces <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>cell growth properties while inducing senescence

Background  

Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown.     

<Emphasis Type="Italic">BRAF</Emphasis>/K-<Emphasis Type="Italic">ras</Emphasis> mutation,microsatellite instability,and promoter hypermethylation of <Emphasis Type="Italic">hMLH1</Emphasis>/<Emphasis Type="Italic">MGMT</Emphasis> in human gastric carcinomas

Background The BRAF and K-ras genes are the most frequently mutated oncogenes in various human malignancies. We examined BRAF and K-ras mutations in human gastric cancer, and investigated their relationship with microsatellite instability (MSI) and the hypermethylation of promoter regions in hMLH1 and O ⁶ -methylguanine DNA methyltransferase (MGMT).Methods Sixteen gastric cancer cell lines and 62 gastric cancer tissue samples were screened for BRAF and K-ras mutations by direct sequencing. We also performed a microsatellite assay and investigated methylation status in the promoter regions of hMLH1 and MGMT.Results mutation was not found in any of the cancer cell lines examined. One (1.6%) cancer tissue sample showed a point mutation in the BRAF gene (GT_G GA_G; V599E). K-ras mutation (GG_T GA_T, G12D) was detected in five (31%) gastric cancer cell lines and in 1 (1.6%) gastric cancer tissue sample. In the gastric cancer tissue samples examined, MSI was detected in 23 (37%) samples. Hypermethylated promoter regions in hMLH1 and MGMT, respectively, were detected in 6 (10%) and 13 (21%) gastric cancer tissue samples. Microsatellite stable (MSS) tumors showed frequent lymphatic invasion (P = 0.050).Conclusion Although BRAF mutation has been reported in a variety of other human cancers, it is a rare event in the carcinogenesis and progression/development of gastric cancer.     

Methylation-mediated silencing and tumour suppressive function of <Emphasis Type="Italic">hsa-miR-124</Emphasis> in cervical cancer

Background  

A substantial number of microRNAs (miRNAs) is subject to epigenetic silencing in cancer. Although epigenetic silencing of tumour suppressor genes is an important feature of cervical cancer, little is known about epigenetic silencing of miRNAs. Since DNA methylation-based silencing of hsa-miR-124 occurs in various human cancers, we studied the frequency and functional effects of hsa-miR-124 methylation in cervical carcinogenesis.     

The relationship between <Emphasis Type="Italic">EGFR</Emphasis> gain and <Emphasis Type="Italic">VHL</Emphasis> loss in lung adenocarcinoma and poor patient survival

Background  

The prognosis of lung cancer remains poor and clinically applicable prognostic markers have not yet been satisfactory identified. Several chromosomal copy number alterations (CNAs) have been associated with metastasis, relapse, and survival of patients with lung cancer; however, no study has focused exclusively on identifying CNAs at a gene level. The aim of this study was to identify genes whose CNAs are associated with survival of patients with lung adenocarcinoma.     

Mutations in <Emphasis Type="Italic">APC</Emphasis>, <Emphasis Type="Italic">CTNNB1</Emphasis> and <Emphasis Type="Italic">K-ras</Emphasis> genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

Background  

The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics.     

Simultaneous down-regulation of tumor suppressor genes <Emphasis Type="Italic">RBSP3/CTDSPL,NPRL2/G21</Emphasis> and <Emphasis Type="Italic">RASSF1A</Emphasis> in primary non-small cell lung cancer

Background  

The short arm of human chromosome 3 is involved in the development of many cancers including lung cancer. Three bona fide lung cancer tumor suppressor genes namely RBSP3 (AP20 region),NPRL2 and RASSF1A (LUCA region) were identified in the 3p21.3 region. We have shown previously that homozygous deletions in AP20 and LUCA sub-regions often occurred in the same tumor (P < 10^-6).     

Novel mutations in the <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis>genes in Iranian women with early-onset breast cancer

Background  

Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population.     

<Emphasis Type="Italic">PTTG</Emphasis>/securin activates expression of <Emphasis Type="Italic">p53</Emphasis> and modulates its function

Background  

Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed abundantly in most tumors. Overexpression of PTTG induces cellular transformation and promotes tumor formation in nude mice. PTTG has been implicated in various cellular processes including sister chromatid separation during cell division as well as induction of apoptosis through p53-dependent and p53-independent mechanisms. The relationship between PTTG and p53 remains unclear, however.     

Managing Patient with Mutations in <Emphasis Type="Italic">PALB2</Emphasis>, <Emphasis Type="Italic">CHEK2</Emphasis>, or <Emphasis Type="Italic">ATM</Emphasis>

Purpose of Review

The use of panel testing of multiple cancer-causing genes has allowed to find a subset of patients with harmful mutations in moderate penetrance genes. While extensive information is available regarding patients with BRCA1 and BRCA2 pathogenic variants, information regarding these less common genes and their management remains scarce. The aim of this review is to discuss penetrance, incidence, and management recommendations for PALB2, ATM, and CHEK2.

Recent Findings

NCCN guidelines now provide management recommendation for patients with pathogenic variants in these genes. In addition, more widespread testing has provided more information on penetrance and incidence. Although this is a huge step toward improving quality of care, prospective studies are still needed. We summarize the NCCN and other guidelines/suggestions for these genes and deliver our insight on the matter based on the best information we could find.

Summary

PALB2, ATM, and CHEK2 are less penetrant than BRCA1–2 and have a different spectrum, suggesting differing management. Data about incidence and penetrance along with management recommendations for these genes are provided.

     

Dysregulated <Emphasis Type="Italic">miR-183</Emphasis> inhibits migration in breast cancer cells

Background  

The involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.