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At least 919 records · Page 51Linked to original sources
PubMed2005

Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses.

PURPOSE: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease. EXPERIMENTAL DESIGN: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance. RESULTS: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemo-response data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002). CONCLUSIONS: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.

ATP-Binding Cassette Transporters↗
PubMed2004

Anticipated reactions to genetic testing for hereditary non-polyposis colorectal cancer susceptibility.

Genetic testing for cancer susceptibility (e.g. hereditary non-polyposis colorectal cancer) is available for some families with a history of colon cancer. Our aim was to investigate participants' anticipated emotional and behavioral reactions to genetic testing for colon cancer and whether gender or clinical risk influences these reactions. 437 asymptomatic participants with a colorectal cancer family history completed a questionnaire about anticipated emotions and actions, under different genetic testing scenarios. More women than men anticipated feeling worried, regretful, and angry if tested positive. People at lower-risk anticipated more surprise and disbelief than those at higher-risk. People anticipated feeling more guilt, regret and less relief if they were not tested than if they were. High-risk results were anticipated to increase depression and worry. Most people still wanted screening if at low risk, anticipated leading healthier lifestyles whatever the result, but would make more plans for the future if they were at high risk. Clinical implications are that as anticipated emotional effects of not being tested may be more severe than having a test, people choosing to forgo testing should feel able to reconsider their decision anytime. Most people did not anticipate strong emotional reactions but thought it would change their lifestyle and would like continued clinical surveillance whatever the result.

Attitude to Health↗
PubMed1996

Contributions of molecular genetics to the clinical management of colorectal cancer.

Molecular genetics is a tool that can be learned as a language to assist clinicians in the management of colorectal cancer patients. Following a brief review of the genetic controls of colorectal cancer, the author focuses on the models of the Registry for Familial Adenomatous Polyposis and the Registry for Hereditary Nonpolyposis Colon Cancer to demonstrate most vividly the impact molecular genetics is currently having on the practical management of colon cancer. Recent discoveries of K-ras oncogene mutations in stool cultures and the prognostic implications of mutations of the TP53 and DCC genes are discussed in the context of future applications to the management of patients.

Adenomatous Polyposis Coli↗
PubMed1996

Ascertainment of familial ovarian cancer in the Aberdeen Genetic Clinic.

Ovarian cancer is the fifth most common malignancy in women in the UK. Patients with a family history including ovarian cancer make up nearly 15% of family cancer referrals to the Genetic Clinic in Aberdeen. To date, only one pedigree has been suitable for linkage studies, which has enabled us to target screening more accurately at those people at highest risk. Following discovery of a strong candidate for the BRCA1 gene, direct mutation testing may soon be possible. People who seek testing will require further counselling. Therefore we anticipate an increased demand on both clinical and laboratory resources, but more accurate ascertainment of high risk subjects should lead to more appropriate targeting of screening services.

Adult↗
PubMed2001

Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer.

In order to detect the contribution of cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), glutathione S-transferases M1 (GSTM1), P1 (GSTP1), and T1 (GSTT1) genes in breast cancer, genetic analysis was performed, as well as transcriptional analysis in sporadic primary tumours and corresponding adjacent normal tissues from the same patient. CYP1A1 3'-untranslated region (3'-UTR) termed as m1 (MspI) polymorphism and the null(-) deletions of both GSTM1 and GSTT1 genes were examined in genomic DNA from blood samples of 207 female breast cancer patients and 171 age and sex matched controls. The frequencies of the m1 genotype of the CYP1A1 gene in cases and controls were 0.13 and 0.15, while the frequencies of homozygotes with GSTM1(-) were 0.52, in each, and for homozygotes with GSTT1(-) were 0.14 and 0.10, respectively. Statistical analysis of these genotypes in combinations did not reveal any significant difference between the breast cancer population and the control group. Expression of mRNA levels of CYP1A1, GSTM1, GSTP1, GSTT1 and AhR genes in 31 breast cancer patients, revealed inter-individual variation in an independent manner to patient age, genotype, or tumour stage. Eighty-seven percent of the tumour specimens tested were deregulated, compared to their normal counterparts, in at least one locus. Up-regulation of CYP1A1 was observed only when one of the GSTM1 or GSTP1 was down-regulated while the other remained constant. Genotyping analysis did not show any correlation to breast cancer risk. However, RT-PCR analysis provided evidence that CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes are frequently deregulated in breast cancer and could be used as molecular biomarkers for better clinical management of such patients, with respect to chemotherapy.

Adult↗
PubMed1996

Genetic progression model for head and neck cancer: implications for field cancerization.

A genetic progression model of head and neck squamous cell carcinoma has not yet been elucidated, and the genetic basis for "field cancerization" of the aerodigestive tract has also remained obscure. Eighty-seven lesions of the head and neck, including preinvasive lesions and benign lesions associated with carcinogen exposure, were tested using microsatellite analysis for allelic loss at 10 major chromosomal loci which have been defined previously. The spectrum of chromosomal loss progressively increased at each histopathological step from benign hyperplasia to dysplasia to carcinoma in situ to invasive cancer. Adjacent areas of tissue with different histopathological appearance shared common genetic changes, but the more histopathologically advanced areas exhibited additional genetic alterations. Abnormal mucosal cells surrounding preinvasive and microinvasive lesions shared common genetic alterations with those lesions and thus appear to arise from a single progenitor clone. Based on these findings, the local clinical phenomenon of field cancerization seems to involve the expansion and migration of clonally related preneoplastic cells.

Carcinoma, Squamous Cell↗
PubMed1998

The genetic analysis of cancer.

During the past two decades an overwhelming amount of knowledge has been acquired on the molecular genetics of human cancer. It is now evident that cancer is essentially a genetic disease, arising from inherited and/or somatically acquired mutations at different genetic loci, and that tumourigenesis is a multistep process. Gene mapping studies of inherited cancer syndromes have resulted in the identification of many genes implicated in the initiation of tumours. Importantly, alterations of the same genes were also found to play a role in the development of common, non-familial tumours. The genes involved belong to distinct functional classes, and include proto-oncogenes and tumour suppressor genes, which are regulators of cellular growth and proliferation, cell adhesion and programmed cell death. Another class of cancer susceptibility genes consists of DNA repair genes, which are involved in maintaining genomic stability. In unravelling the genetic basis of cancer, the localization and identification of genes involved in tumourigenesis can be considered as the 'easy' part; determination of the normal physiological function of these genes and their precise role in tumourigenesis has proved to be much more difficult. In this review, we highlight some of the major breakthroughs in the field of cancer genetics, and discuss recent insights in the putative role of proto-oncogenes, tumour suppressor genes and DNA repair genes in the initiation and progression of cancer. Also, we point to some of the challenges to be faced in the coming years.

DNA, Neoplasm↗
PubMed1989

The genetic predisposition to cancer.

The multi-stage nature of cancer, and the interaction of the host and environment in the origin of cancer, both suggest multiple ways in which genetic predisposition to cancer might operate. A role for genetic variation has already been demonstrated in many instances and it is likely that still more examples of genetic predisposition will be uncovered. In some individuals genetic predisposition operates interactively with environment. Much of human cancer may occur in persons of this interactive oncodeme. Other persons have a very strong susceptibility to cancer because they have inherited a mutation on the path to cancer; they belong to a "purely" genetic oncodeme. The population of target cells itself is known to be affected by some environmental agents. Genetic factors may also operate, as in the X-linked lymphoproliferative syndrome with its predisposition to Burkitt lymphoma. Somatic mutation plays a critical role in carcinogenesis. Numerous environmental agents can increase the probability that somatic mutation will occur. Host genes can interact with these factors in two general ways. One concerns the ability to repair the damage caused by the agent. Most of the damage is repaired in normal persons, but much more is not repaired in persons with certain recessively inherited disorders, known as DNA-repair deficiencies. The other general way concerns the delivery of the critical agent. For example, the albino absorbs such excessive amounts of sunlight that even a normal DNA-repair mechanism is stressed. Similarly, some individuals metabolize certain chemical compounds in such a way that the concentration of an active mutagen is abnormally high, again overcoming the DNA-repair mechanism. The stages of promotion, progression, and metastasis are much less well understood, and clear examples of a role for genetic factors in them are not available. However, there are multiple ways in which heredity could be interacting, as with a genetic control of hormone production. Finally, the genetic targets of mutation, the "cancer genes," can play a role in cancer. Although no heritable mutations for oncogenes are yet known in man, there are reasons to believe that they could occur. On the other hand, heritable mutations of anti-oncogenes are well known and apparently account for much, or all, of dominantly heritable cancer in humans. In toto, the contribution of genetic predisposition to the burden of cancer could be considerable, because of the potentially large size of the interactive oncodeme. Identification of such susceptible persons could have important consequences in preventive oncology.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗
PubMed2002

An intronic polymorphism of the hMLH1 gene contributes toward incomplete genetic testing for HNPCC.

Hereditary non-polyposis colorectal cancer (HNPCC) is a common hereditary cancer. Genetic testing is complicated by the multiple DNA mismatch repair genes that underlie the disorder. Many suspected HNPCC families have no germ-line mutation identified. We reassessed an unusual family that appeared to have 2 individuals homozygous for a germline mutation within exon 1 of the hMLH1 gene. A few rare individuals with two inherited mutations in one of the mismatch repair genes have been reported and appear to have a distinct clinical appearance. However, there were no clinical features in the family discussed here that were consistent with constitutive lack of hMLH1. Redesigning the intronic primers for exon 1 identified a common polymorphism located within the original intronic primer site. The polymorphism prevented amplification of the wild-type allele, giving the erroneous appearance of homozygous inheritance of the mutated allele. Likewise, common intronic polymorphisms, if located within primer sequences on the chromosome harboring the HNPCC germ-line mutation could restrict amplification to only the wild-type allele, which may contribute significantly to the low success rate of identifying mutations in HNPCC families.

Adaptor Proteins, Signal Transducing↗
PubMed2003

[The microencapsulated genetic engineering cells: a new platform on treatment of cancer instead of genetic engineering drugs].

The microencapsulated genetic cells may be a new platform instead of genetic engineering drugs, as they can overcome the genetic engineering drugs' shortages such as short half-life in vivo, low activity, and incomplete elimination of organic solvent. This article reviews and summarizes the advantages, possible problems and solution and the feasibility of using microencapsulated genetic engineering cells in the treatment of cancer.

Animals↗
PubMed2002

Pancreatic cancer biology and genetics.

Pancreatic ductal adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression and profound resistance to treatment. Advances in pathological classification and cancer genetics have improved our descriptive understanding of this disease; however, important aspects of pancreatic cancer biology remain poorly understood. What is the pathogenic role of specific gene mutations? What is the cell of origin? And how does the stroma contribute to tumorigenesis? A better understanding of pancreatic cancer biology should lead the way to more effective treatments.

Adenocarcinoma↗
PubMed2006

Risk reduction behaviors and provider communication following genetic counseling and BRCA1 mutation testing in an African American kindred.

Little is known about the impact of cancer genetic counseling and testing on health behaviors in racial and ethnic subgroups. This prospective observational study examined use of risk reduction strategies following BRCA1 counseling and testing. Participants were female members of an African American kindred who received genetic education, counseling and testing (n = 40) and completed a 1-year follow-up interview. Mutation carriers were more likely to opt for breast (100%, 7/7) and ovarian (25%; 1 of 4) cancer surveillance than prophylactic surgery. Following genetic counseling, 71% (5/7) of the BRCA1 carriers who opted for surveillance reported having a mammogram within the year following receipt of their genetic test results. Ovarian cancer screening among mutation carriers increased from 0% at baseline to 25% (one of four) at 1 year. Compared to noncarriers (23%, 7/30), carriers (70%, 7/10) were more likely to discuss their BRCA1 test results with their primary health care providers. Surveillance for breast cancer was preferred to prophylactic surgery and chemoprevention as a way to reduce risk for these cancers. Our data indicate that patient-provider communication about BRCA1 test results is suboptimal.

Adult↗
PubMedDate not supplied

[Interactions between genetics and environment].

From a scientific point of view, the idea that genes exert an important role in explaining human pathology has gained much popularity in recent decades. However, according to Stephen Jay Gould, the "genetic fallacy" has been repeatedly used to avoid environmental action. In the case of occupational cancer, genetic screening of workers for their susceptibility to the action of chemical carcinogens, on the basis of "metabolic polymorphisms", would be unacceptable because of racial discrimination, related to uneven racial distribution of most polymorphisms, for example, 90% of Africans and 10% of Asians have the "slow" acetylator genotype. Therefore, not only technical and scientific aspects of genetic susceptibility to cancer, but also ethical and social implication have to be considered.

Aged↗
PubMed2003

Colon cancer: prevalence, screening, gene expression and mutation, and risk factors and assessment.

Colon cancer detection at an early stage and identifying susceptible individuals can result in reduced mortality from this prevalent cancer. Genetic events leading to the development of this cancer involve a multistage progression of adenoma polyps to invasive metastatic carcinomas. Currently, there is no satisfactory screening method that is highly specific, sensitive, or reliable. Dietary patterns associated with the greatest increase in colon cancer risk are the ones that typify a diet rich in fat and calories, and low in vegetable, fruits, and fibers. Genetic susceptibility to environmental carcinogenesis must be factored into the risk assessment for this cancer. Many genes have been shown to be associated with increased expression and mutations in colorectal cancer patients. These genes have been reviewed; it is hoped that by carefully selecting a number of them, a molecular approach that is suitable for arriving at a tumorigenic expression index is developed, which will reliably detect this cancer at an early stage (i.e., before it metastasizes), especially in exfoliated samples (e.g., stool and blood), so that appropriate intervention strategies can be implemented. Illustrated herein is the utility of employing real-time reverse transcriptase polymerase chain reaction (RT-PCR) to quantitatively measure gene expression, and develop an index that is specific for this cancer, which if perfected may result in a reliable and sensitive screening technique for colorectal cancer detection.

Adenomatous Polyposis Coli↗
PubMed2026

Large-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes.

Pleiotropic genetic loci have been increasingly reported in cancer, and identifying genetic variants with pleiotropic associations can reveal shared biological pathways influencing multiple cancers. Using summary statistics from genome-wide association studies for 37 cancer types (N = 433 836), we identified extensive genome-wide and local genetic correlations among cancers. Through pairwise pleiotropic analysis, we identified 75 243 significant pleiotropic single nucleotide polymorphisms (SNPs) across 372 cancer pairs, among which 3472 were lead SNPs with potential regulatory functions. Using FUMA and MAGMA, we identified 2527 pleiotropic risk loci and 4272 candidate pleiotropic genes. Notably, genes such as TERT (5p15.33), POU5F1B (8q24.21), and FANCA (16q24.3) exhibited widespread pleiotropy across multiple cancer types. Pathway enrichment analysis highlighted the critical roles of pigment synthesis, metabolism, and apoptosis in skin-related cancers, while cross-cancer enrichment analysis emphasized pathways related to apoptosis, chromatin structure, and intermediate filaments. We also identified 33 novel functional genes harboring previously unreported cancer risk variants. Drug-gene interaction analysis revealed several repositionable FDA-approved drugs. Importantly, drug sensitivity assays demonstrated that bosutinib and cobimetinib exhibited promising therapeutic potential in breast cancer cell lines. Finally, we developed the PleioCancer database (https://gonglab.hzau.edu.cn/PleioCancer/), providing a comprehensive resource for cancer pleiotropy research. These findings have important implications for carcinogenesis cancer, prevention and treatment.

Humans↗
PubMed2006

Familial neuroendocrine tumor syndromes: from genetics to clinical practice.

Thanks to recent developments in molecular biology and cancer genetics, genetic testing has become widely available and useful in several kinds of familial tumor syndrome. However, the impact of genetic testing on medical management is not always straightforward. Clinicians have to consider the psychological impact and ethical complexities of communicating hereditary cancer risk information to families. This review notes some points on genetic counseling before and after genetic testing for familial neuroendocrine tumor syndromes.

Adult↗
PubMed1982

[Clinical and genetic study on human cancer--gastric cancer].

The relationship between gastrointestinal cancers and genetic influence was investigated. The subjects examined were 1211 cancer cases and 781 non-cancer cases registered to the 1st Department of Surgery of Kagoshima University Hospital from 1972 to 1980. The results were as follows: 1. Malignant cases were found in 266/1211 (22.0%) in the families of cancer probandus. Incidence was significantly (P less than 0.01) higher than that [130/781 (16.6%)] in those of non-cancer probandus. 2. Malignant cases were found in 79/356 (22.2%) in the families of gastric cancer probandus and in 51/189 (27.0%) in those of colo-rectal cancer probandus. 3. The relationship between cancer probandus and malignant cases in the families was classified according to the vertical relationship (grandparents-parents-uncle and aunt-probandus-children) and the horizontal relationship (probandus-siblings-cousin). 4. Incidence in the vertical relationships (159/266: 59.8%) was higher than that in the horizontal relationships (107/266: 40.2%). Incidence of the vertical relationships of female cancer probandus (gastric cancer: 70.4%, esophageal cancer: 55.7%, clorectal cancer: 73.9%) was significantly (P less than 0.05) higher than that in those of male cancer probandus. 5. Incidence of blood B type in male gastric cancer group tended to be less when compared with the control group (P less than 0.05). 6. Incidence of smoking habits in esophageal cancer group (82.2%) and the lung cancer group (63.4%) was significantly (P less than 0.01) higher than that in the control group (46.0%). 7. Incidence of drinking habits in the male esophageal cancer group (84.2%) was significantly (P less than 0.01) higher than that in the control group (53.0%).

ABO Blood-Group System↗
PubMed2000

[Genetic changes in breast cancer - an overview].

Current understandings about development of breast cancer from genetic point of view are discussed. Information about the hereditary forms of cancer is presented. Different forms of screening and problems connected with their application are discussed.

BRCA1 Protein↗