Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans approximately 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.
 ...
PMID:A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumors distal to BRCA1. 794 44

Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have suggested that chromosome 17q may be the location of a gene of importance in ovarian carcinogenesis. We have examined tumor and normal DNA samples from 120 patients with ovarian tumors for allelic deletion at 12 loci on chromosome 17q. Allelic deletion was observed in 64 cases (53%) of which 56 showed loss of heterozygosity at all loci analyzed on 17q. The pattern of allele loss at metastatic sites was consistent with loss of heterozygosity having occurred prior to metastasis. A common region of deletion, defined by 6 cases of invasive epithelial ovarian cancer and a benign serous cystadenoma, spanned 16 cM and was delimited by nm23 and GH. This region is distal to the region on chromosome 17q to which the familial breast/ovarian cancer susceptibility gene has been mapped. The results suggest that a tumor suppressor gene involved in sporadic ovarian carcinogenesis is located on the distal portion of chromosome 17q and is distinct from the gene linked to familial cases.
 ...
PMID:A deletion unit on chromosome 17q in epithelial ovarian tumors distal to the familial breast/ovarian cancer locus. 809 78

Thirty-seven ovarian cancer-prone families have been identified through a French co-operative network. Three main clinical presentations were observed: site-specific ovarian cancer, breast/ovarian carcinoma syndrome and Lynch syndrome II. An additional kindred with features of Li-Fraumeni syndrome is reported. It is expected that a better understanding of the mechanisms of carcinogenesis will allow the development of new methods of screening and treatment. With this aim, recent studies have mapped the gene for early-onset familial breast cancer and breast/ovarian carcinoma syndrome to the same locus in the chromosome 17q12-q23 region. Results from linkage analysis of two breast/ovarian carcinoma families and three breast cancer families favour the hypothesis of genetic heterogeneity among breast and ovarian tumors.
 ...
PMID:Familial ovarian carcinoma: pedigree studies and preliminary results from linkage analysis. 817 63

A predisposing gene (BRCA-1) for breast and ovarian cancer has been located on chromosomal region 17q12-21. According to Knudson's hypothesis if this gene is a tumor suppressor gene, allelic losses would be found in tumors occurring in families with cancer aggregations. We studied 25 samples of both benign lesions and malignant tumors, from breast cancer site-specific families and other familial cancer aggregations. Allelic losses seem to be more frequent in tumors from breast site-specific families but also include the predisposing locus in other syndromes, suggesting a role of BRCA-1 in such families. Finding of allele losses near this locus in benign lesions suggests that such alterations may represent a first step in breast carcinogenesis. It is noteworthy that allele losses involve larger chromosome fragments in malignant tumors than in benign lesions where BRCA-1 is not lost, suggesting a similar mechanism for genomic deletion in the tumorigenesis of the colon and of the breast.
 ...
PMID:Detection of allelic losses on 17q12-q21 chromosomal region in benign lesions and malignant tumors occurring in a familial context. 829 Feb 55

Multiple loss of heterozygosity (LOH) studies of ovarian cancers have found a high incidence of chromosome 17 loss in these tumors. Several authors have suggested that the region commonly deleted encompasses 17q12-21. In addition, this region has recently been reported to be linked to the familial breast/ovarian cancer syndrome. Recently the human prohibitin gene was mapped to region 17q12-22. Prohibitin causes arrest of DNA synthesis by fibroblast and HeLa cells and prohibitin shows significant homology to a gene (Cc) thought to be important for the regulation of development of Drosophila melanogaster. These findings have led many to consider the prohibitin gene a potential tumor suppressor gene. In addition, sequence analysis of exon 4 of human prohibitin gene revealed mutations in 4 of 23 sporadic breast carcinomas. Because of the proposed function for prohibitin, its alterations in breast cancers, and the fact that its location on 17q falls within a commonly deleted region in ovarian cancers, we have undertaken an analysis of the sequence of prohibitin in epithelial ovarian cancers. Using several polymorphic DNA probes, we identified 20 epithelial ovarian tumors which demonstrated LOH for the region that contains the prohibitin gene. To evaluate whether mutations of prohibitin may be important in ovarian carcinogenesis, we have sequenced exons 4 and 5 of this gene using the technique of genomic amplification with transcript sequencing. Only normal exon 4 and 5 sequence was observed among the 20 tumors screened. These results demonstrate that this region of the prohibitin gene is not mutated in epithelial ovarian cancers and suggest that the prohibitin gene does not play a role in ovarian carcinogenesis. Sequencing of further exons and introns are needed to confirm this latter hypothesis.
 ...
PMID:Absence of prohibitin gene mutations in human epithelial ovarian tumors. 834 62

Amplification of the HER-2/neu oncogene was assessed in 80 cases of epithelial ovarian tumors using differential polymerase chain reaction. HER-2/neu gene was amplified in 22 of 46 invasive cancers (48%) and in 5 of 34 borderline cancers (15%), but none of the 20 specimens of normal ovaries showed amplification. THis difference is statistically significant (p = 0.00004). The incidence of HER-2/neu amplification in late stage (III-IV, 77%) was significantly higher than that in early stage (I-II, 21%) in invasive epithelial carcinoma (p = 0.0004). There was no correlation between HER-2/neu amplification and cell type or grade of tumor. In cases of ovarian tumors of borderline malignant potential, the amplification of HER-2/neu was not correlated with clinicopathologic features. Follow-up with a mean of 22 months (6-50 months) was available for 39 cases of invasive ovarian cancers and all 34 borderline ovarian cancers. The incidence of HER-2/neu amplification in the invasive cancer and borderline cancer patients who were alive with disease was 50 and 50%, and is not statistically different from that in the patients who were alive with no evidence of disease (p = 0.662 and 0.345, respectively). The incidence of amplification in the invasive cancers of patients who died of the disease (86%) was higher than that in the patients who were still alive (44%), but the difference is not statistically significant (p = 0.175). This study supports the association of HER-2/neu amplification with progression of invasive ovarian cancer. It also suggests that HER-2/neu amplification may be an adjunctive prognostic factor of invasive epithelial ovarian cancer, shown to be associated with an unfavorable clinical course. In addition, HER-2/neu amplification occurs relatively infrequently in early invasive and borderline ovarian cancers, making it unlikely that such amplification is a general early event in ovarian carcinogenesis.
 ...
PMID:Prevalence and significance of HER-2/neu amplification in epithelial ovarian cancer. 852 57

Hormones play a major role in the aetiology of several of the commonest cancers worldwide, including cancers of the endometrium, breast and ovary in women and cancer of the prostate in men. It is likely that the main mechanisms by which hormones affect cancer risk are by controlling the rate of cell division, the differentiation of cells and the number of susceptible cells. Hormones have very marked effects on cell division in the endometrium; oestrogens stimulate mitosis whereas progestins oppose this effect. The risk for endometrial cancer increases with late menopause, oestrogen replacement therapy and obesity, and decreases with parity and oral contraceptive use; thus risk increases in proportion to the duration of exposure to oestrogens unopposed by progestins, probably because unopposed oestrogens stimulate endometrial cell division. The effects of hormones on breast epithelial cell division in non-pregnant women are much less clear-cut than their effects on the endometrium, but both oestrogens and progestins appear to stimulate mitosis. Breast cancer risk increases with early menarche, late menopause and oestrogen replacement therapy, probably due to increased exposure of the breasts to oestrogen and/or progesterone. Early first pregnancy and multiparity reduce the risk for breast cancer, probably due to the hormonally-induced differentiation of breast cells and the corresponding reduction in the number of susceptible cells. Hormones do not have marked direct effects on the epithelial cells covering the ovaries, but hormones stimulate ovulation which is followed by cell division during repair of the epithelium. Risk for ovarian cancer increases with late menopause and decreases with parity and oral contraceptive use, suggesting that the lifetime number of ovulations may be a determinant of risk. For all three of these cancers risk changes within a few years of changes in exposure to sex hormones and some of the changes in risk persist for many years, indicating that hormones can affect both early and late stages of carcinogenesis. Understanding of the role of sex hormones in the aetiology of prostate cancer and of some rarer cancers is less complete.
 ...
PMID:Hormones and cancer in humans. 853 37

Targeting dysfunctional gene expression in the cancer cell with gene-specific therapeutics requires knowledge of the structure and expression of the designated gene. Because of the prevalence of p53 dysfunction in epithelial ovarian carcinoma, modulation of the expression of this tumor suppressor gene is an attractive target for gene therapy. We sequenced the p53 gene and analyzed its expression in 10 ovarian cancer cell lines. Only five cell line mutations were encountered, three associated with a loss of heterozygosity. Thus, neither p53 mutation nor allelic loss is required for ovarian carcinogenesis or propagation of ovarian cancer cell lines in vitro. SSCP screening, but not immunohistochemical staining, correlated with results of direct genomic sequencing. All p53 immunohistochemical-negative cell lines differed from that reported by another laboratory, underscoring the importance of the knowledge of target gene expression in a given cell line in a given laboratory. We designed pilot studies of antisense oligodeoxynucleotides directed against the p53 gene based on our sequence data. Differential growth inhibition of the A2780-CP-20 cell line (mutant p53 protein), but not of the OVCAR-3 cell line (wild-type p53 protein) confirmed the potential usefulness of this strategy.
 ...
PMID:p53 gene mutation analysis and antisense-mediated growth inhibition of human ovarian carcinoma cell lines. 855 31

To investigate the putative role of BRCA1, a gene involved in hereditary breast and ovarian cancer, in sporadic ovarian tumors among Japanese women, we examined 76 unselected primary ovarian cancers for mutations in the coding region of BRCA1 using the single-strand conformation polymorphism technique. Although no somatic mutations were detected in any of the tumors, constitutional mutations were identified in four cases: two frameshifts, one nonsense mutation and one intronic base substitution 32 bp downstream of exon 22; RT-PCR experiments revealed that the single-base substitution in the intron seemed to increase the transcript lacking exon 22. All four cases were judged to involve truncation of the gene product. The evidence reported here supports a rather limited role of BRCA1 in ovarian carcinogenesis in the Japanese population.
 ...
PMID:Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation. 859 20

The following review considers epidemiological data published from 1990 onwards on oral contraceptives (OCs) and the risk of cancers of the breast, cervix uteri, endometrium, ovary, liver and skin. In several studies, breast cancer risk was seen to be elevated among women who were current users of an OC, or had recently stopped using an OC, whereas there was no residual risk 5 or more years after stopping OC use. No interaction was observed between type of OC, or with any recognised risk factor for breast cancer, or time-factor, except for some potential excess risk for women who started OC use at a young age. Most studies have confirmed that OCs moderately increase the risk of cervical cancer, particularly in human papilloma virus (HPV)-positive women, thus suggesting that OCs may act as a promoter for HPV-induced carcinogenesis. Recent epidemiological studies have confirmed that combined OCs provide substantial protection against endometrial and ovarian cancers, and results suggest that such protection is long-lasting, and may persist for 15 years or more after stopping OC use. Most case-control studies have shown a relationship between OC use and hepatocellular carcinoma. However, data from cohort studies or analysis of vital statistics indicate that the public health impact of such an association is modest, if not negligible. No association was observed between combined OC use and the incidence of skin melanoma, or any other common skin neoplasm. In terms of clinical and public health implications, the most relevant points regarding OC use are: (i) recent data confirm that OCs confer presistent protection against ovarian cancer; and (ii) any increased risk of breast cancer in OC users is moderate and is restricted to current/recent users. This is reassuring for younger women, whose baseline risk of this disease is extremely low.
 ...
PMID:Oral contraceptives and cancer. A review of the evidence. 871 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>