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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of genes are known to be involved in inherited susceptibility to breast and/or ovarian cancer. In the context of high-risk families the most important genes are BRCA1 on chromosome 17q, which is associated with a high penetrance of both breast and ovarian cancer, and BRCA2 on chromosome 13q, which causes a high risk of breast cancer but a lower risk of ovarian cancer. Other high-risk cancer genes that confer increased risks of breast or ovarian cancer in addition to other cancers include the hereditary non-polyposis colorectal cancer genes and the TP53 gene, which causes breast cancer as part of the Li-Fraumeni syndrome. The predisposing mutations in these genes are relatively rare in the population. More common genes which are associated with an increased, but lower, risk of breast cancer are the ataxiatelangiectasia gene and the HRAS1 gene. This paper reviews recent progress in mapping and cloning of these susceptibility genes, and provides estimates of the cancer risks associated with each gene and the frequency of predisposing mutations.
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PMID:The genetics of breast and ovarian cancer. 754 24

Using a polymerase chain reaction/microsatellite marker system, we demonstrated that 6 of 22 (27%) clinical stage B (early) primary prostate tumors showed loss of heterozygosity at one or more of five loci on chromosome 17. The sensitivity of this study was increased by use of a PhosphorImager and statistical analysis of replicate tumor-normal DNA pairs. Two patients showed tumor-specific interstitial loss at a locus in close proximity to the familial breast cancer gene BRCA1. These findings suggest that genes on the proximal long arm of chromosome 17 play a pivotal role in the early development of at least a subset of prostatic tumors.
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PMID:Loss of chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers. 754 36

Since BRCA1, the first major gene responsible for inherited breast cancer, was cloned, more than 50 unique mutations have been detected in the germline of individuals with breast and ovarian cancer. In high-risk pedigrees, female carriers of BRCA1 mutations have an 80-90% lifetime risk of breast cancer, and a 40-50% risk of ovarian cancer. However, the mutation stats of individuals unselected for breast or ovarian cancer has not been determined, and it is not known whether mutations in such individuals confer the same risk of cancer as in individuals from the high-risk families studied so far. Following the finding of a 185delAG frameshift mutation in several Ashkenazi Jewish breast/ovarian families, we have determined the frequency of this mutation in 858 Ashkenazim seeking genetic testing for conditions unrelated to cancer, and in 815 reference individuals not selected for ethnic origin. We observed the 185delAG mutation in 0.9% of Ashkenazim (95% confidence limit, 0.4-1.8%) and in none of the reference samples. Our results suggest that one in a hundred women of Ashkenazi descent may be at especially high risk of developing breast and/or ovarian cancer.
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PMID:The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. 755 Mar 31

BRCA1 mRNA and protein levels are regulated by the steroid hormones estrogen and progesterone in human breast cancer cells. BRCA1 mRNA and protein levels were significantly decreased in estrogen-depleted MCF-7 and BT20T cells and increased again after stimulation with beta-estradiol. The increase in BRCA1 expression upon stimulation with estrogen was not coordinated with the early induction of the estrogen-dependent pS2 gene but closely paralleled the delayed increase in the S-phase dependent marker cyclin A. T47-D cells deprived of steroid hormones and subsequently stimulated with progesterone also showed a delayed increase in BRCA1 mRNA expression. However, no change in BRCA1 protein was detected in these cells. When considered together, the data suggest that steroid hormones may affect BRCA1 expression indirectly by altering the proliferative status of the cells rather than acting directly on DNA sequences in the BRCA1 gene itself.
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PMID:Hormone-dependent regulation of BRCA1 in human breast cancer cells. 755 29

The submitted account on genes of the 17th chromosome pays attention to autosomal dominant hereditary neurodegenerative diseases which have some characteristics in common-they are relatively frequent, a considerable proportion of the cases is conditioned by new mutations, contributed mainly by male gametes, and they affect mostly the periphery of the nervous system. In addition to the cause of this group of diseases which at present is not yet quite clear, the 17th chromosome is the carrier of the locus the product of which--p53 protein--interferes with oncogenesis. Its effect twofold--the normal product under normal conditions (natural regulation) exerts an antioncogenic action, its shortage or altered quality-(mutations) exert an oncogenic action. Another important locus which is involved in oncogenic processes is locus RARA--the receptor of retinoic acid which participates in the formation of promyelocytic acute leukaemia and locus BRCA1 the pathogenic alleles of which are a dominant predisposition for breast cancer.
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PMID:[The human genome--chromosome 17]. 755 59

Because of a family history of breast cancer, a 51-year-old patient underwent bilateral subcutaneous mammectomy in 1988. In February 1994 she presented with a nodule in the supramedial quadrant on the left. Needle biopsy suggested galactophoric adenocarcinoma which was confirmed histologically. A 1.5 cm tumour was removed together with a 3 cm reliquat of glandular tissue. Twelve axillary nodes were dissected and were found to be free of neoplastic infiltration. Hormone receptors were positive. Post-operative radiotherapy was performed. The outcome is unchanged at 6 months. Bilateral subcutaneous mammectomy can be proposed as a preventive measure in patients at risk, but as demonstrated by this case, exeresis is usually incomplete. The level of protection actually achieved is thus questionable. Clinicians should be aware of the risk of breast cancer developing after such elective operations since early screening programmes and the development of genetic methods based on the search for BRCA1 and BRCA2 genes will undoubtedly increase the number of patients requesting preventive measures.
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PMID:[Breast cancer after preventive subcutaneous mastectomy]. 756 34

There is now unequivocal evidence that an estimated 5% of breast cancer cases is inherited in families. Inherited predisposition of cancer in these families is thought to be the result of a mutation in one of several highly penetrant autosomal dominant genes such as BRCA1 or BRCA2. The BRCA1 gene which is localized on chromosome 17 q was recently isolated and at about the same time BRCA2 was localized to chromosome 13 q. A number of other genetic mutations is also associated with predisposition to breast cancer but accounts for a very small proportion of inherited breast cancer. Many women want to know whether they have inherited a gene predisposing to breast cancer. Those with a family history of breast cancer are particularly concerned about their risk of disease. Currently the assessment of an individual's risk of breast cancer can be undertaken using prediction models based on family history and can be further refined when molecular genetic investigations became available. Without molecular characterisation the Claus tables derived from the Cancer and Steroid Hormone Study data set are best suited to predict breast cancer risk based on age of onset of affected relatives. Direct screening for mutations in breast cancer genes in not yet generally available. Testing for inherited susceptibility is currently being offered to selected families where multiple cases of breast and/or ovarian cancer are diagnosed at an early age (younger than 45 years) as part of research protocols. In these families the so-called indirect gene analysis for linkage of disease to BRCA1 and BRCA2 or the direct analysis of mutations with functional significance in the BRCA1 gene allows relatively refined risk assessment for non-diseased female family members. Some examples will be presented to illustrate risk assessment in different familial and individual situations. Risk assessment including test result interpretation and counselling can be appropriately provided directly to the patient by physicians and genetic counsellors in a coordinated genetic counselling setting.
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PMID:[Risk assessment for familial occurrence of breast cancer]. 757 5

Humans show heterogeneous susceptibility to cancer development, suggesting the involvement of various genetic backgrounds in control of the production of endogenous carcinogens, the metabolism of carcinogens, the repair of DNA damage, cell proliferation and defence mechanisms including immune reactions. Gastric cancer is the major cancer in Japan. However, little is known about the genes linked with its development. In 1967, we found that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced gastric cancers in Wistar rats. Subsequently the Buffalo strain of rats was reported to be resistant to MNNG stomach carcinogenesis, while ACI rats were very sensitive. In a carcinogenesis study using F1 and F2 rats, we suggested that this trait of MNNG stomach carcinogenesis-resistance was regulated by a single autosomal dominant allele. The O6-methylguanine adduct levels in gastric mucosa induced by MNNG were the same in Buffalo and ACI rats, but cell proliferation induced by MNNG was much higher in ACI than Buffalo animals. Chromosome mapping of the gene responsible for susceptibility to MNNG-induced carcinogenesis is now in progress and its identification will hopefully give us clues to the involvement of genetic traits in susceptibility to gastric cancer in humans. In addition, the genetic background of susceptibility to breast cancer is also being studied. In Japan, about 5% of all cases of breast cancer are familial. We have studied BRCA1, the breast cancer susceptibility gene, as a determinant of susceptibility to breast cancer by linkage analyses in 11 families, but our results indicate that BRCA1 may not be important for development of familial breast cancer in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic polymorphisms and susceptibility to cancer development. 758 88

The high incidence of breast cancer and/or ovarian cancer in some families appears to be due to germ-line mutations in BRCA1. Genetic analysis of such families suggests that the BRCA1 candidate region lies between D17S857 and D17S78 on chromosome 17q21 (Kelsell et al. 1993; Simard et al. 1993). To identify and isolate BRCA1, we have used linkage and meiotic recombination analysis, characterized regions displaying LOH in tumor DNA from BRCA1-linked families, performed YAC and cosmid clone isolation and ordering, and used three complementary transcript-searching strategies. We have identified as many as 28 genes from the BRCA1 candidate region, and we are searching for constitutive mutations in these candidate genes by several methods in an attempt to identify BRCA1.
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PMID:Progress toward isolation of a breast cancer susceptibility gene, BRCA1. 758 9

We have isolated genomic and cDNA clones of Brca1, a mouse homolog of the recently cloned breast cancer-associated gene, BRCA1. Brca1 encodes an 1812-amino-acid protein with a conserved zinc finger domain and significant homology to the human protein. Brca1 maps to Chromosome 11 within a region of conserved synteny with human chromosome 17, consistent with the mapping of the human gene to 17q21. Brca1 transcripts are expressed in a variety of cultured cells but reveal a specific and dynamic expression pattern during embryonic development. For example, expression is observed first in the otic vesicle of embryonic day 9.5 (E9.5) embryos. This expression diminishes and is replaced by expression in the neuroectoderm at E10.5. By E11-12.5, higher levels are observed in differentiating keratinocytes and in whisker pad primordia. Transcripts also become evident in epithelial cells of the E14-17 kidney. Brca1 expression occurs in differentiating epithelial cells of several adult organs as well, suggesting a general role in the functional maturation of these tissues. Consistent with this, Brca1 transcripts are expressed in both alveolar and ductal epithelial cells of the mammary gland. During pregnancy, there is a large increase in Brca1 mRNA in mammary epithelial cells, an increase that parallels their functional differentiation. Because high rates of breast cancer are associated with loss of BRCA1 in humans, it is possible that this gene provides an important growth regulatory function in mammary epithelial cells. In addition, increased transcription of mammary Brca1 during pregnancy might contribute, in part, to the reduced cancer risk associated with exposure to pregnancy and lactation.
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PMID:Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice. 759 Feb 47


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