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

Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.
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PMID:Genetic heterogeneity in breast cancer susceptibility. 869 52

A proportion of familial breast cancer has recently been shown by genetic linkage analysis to map to chromosome l3q12 (Wooster et al, 1994). This locus contains a tumor suppressor gene BRCA2, mutations in which lead to tumorigenesis. Genetic alterations at this locus have also been shown in pancreatic adenocarcinoma and in hepatocellular carcinoma. In an effort to isolate the BRCA2 gene, we have cloned 73 non overlapping cDNAs from a set of nine YACs spanning 6 cM interval on chromosome 13q12 by using a direct cDNA selection method. One of the selected cDNAs corresponds to a region of the 3' portion of BRCA2 mRNA, the sequence of which was published recently (Wooster et al, 1995). Northern analysis of BRCA2 transcripts from a variety of cell lines showed altered sizes of the mRNA in a breast cancer cell line (MCF7) and a prostate carcinoma cell line (DU145). Furthermore, BRCA2 transcript was present in cDNA libraries from total fetus as well as adult human tissues. Fifteen unique cDNA fragments encode genes/ESTs that are already known, of which only two have been mapped to this region. The other 12 cDNAs include genes for RPL6/mRNA for TAX REB 107, elongation factor-1 delta, 26S protease S4 regulatory subunit, small cytoplasmic 7SL RNA, a full length open reading frame (ORFU), brain thiol specific antioxidant protein, ribosomal protein, L35, and lipoxygenase activating protein. Six cDNAs represent human homologs of genes known in other species, namely, mouse HSPE71, Rat RhoGAP protein, S cerevisiae leucyl tRNA synthetase and S cerevisiae chromosome II ORF YBLO44W. The remaining 52 cDNAs showed either weak similarity or no similarity to sequences in the nucleotide data base and hence would represent novel genes. The plausible functions of some of these genes based on their sequence similarity to other known genes is discussed.
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PMID:Isolation of expressed sequences that include a gene for familial breast cancer (BRCA2) and other novel transcripts from a five megabase region on chromosome 13q12. 870 May 50

Studies on Icelandic breast cancer families have shown that most of them segregate a 999del5 BRCA2 mutation. Here, we report the frequency of the 999del5 BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types. The proportions of individuals carrying the mutation were 0.4% in the control population and in the patient groups 8.5%, 7.9%, 2.7%, and 1.0%, respectively. Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.
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PMID:High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients. 870 4

Human carcinomas are generally considered to develop through the accumulation of various genetic abnormalities. The major types of genetic alterations that are frequently observed in breast cancer are amplification of protooncogenes (MYC, ERBB2); mutation of TP53; and loss of heterozygosity on chromosomes 1, 3p, 8p, 11p, 13q, 17q, 17, and 22q. The latter may correspond to losses or inactivations of tumor suppressor genes. Recently, two major distinct breast susptibility genes were isolated, namely BRCA1 and BRCA2. We performed PCR-SSCP analysis to determine the role of the BRCA1 gene in Japanese breast cancer and investigated how multiple genetic alterations contribute to tumor development and/or progression in primary breast cancer, using a large number of tumor materials.
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PMID:[Genetic alterations and DNA-based diagnosis in breast cancer]. 870 40

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.
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PMID:A novel p53 germline alteration identified in a late onset breast cancer kindred. 871 Mar 80

A major risk factor for breast cancer is family history of the disease in first-degree relatives. This study evaluates the validity of family history information on breast cancer in mothers and sisters of breast cancer probands from the cancer registry (CR) compared to personal interviews (PI) of 359 consecutive population-based cases of breast cancer. Breast cancer is seen in mothers of 14% of probands by CR compared to 12% by PI. Further, 13% of probands have a sister with breast cancer using CR compared to 12% by PI. Using PI as the standard, the sensitivity of the CR family history data in mothers is 92% and the specificity is 99%, while in sisters they are 88% and 99%, respectively. These estimates were calculated on cases where family history information is available in the CR. Sensitivity and specificity are recalculated, recording an "error" whenever family history information is not available, and they are 75% and 68%, respectively, for mothers and 72% and 70%, respectively, for sisters. Estimates of proband-mother and proband-sisters familial breast cancer from CR and PI are sufficiently similar to warrant the use of CR family history data in studies of genetic epidemiology. The family phenotype consistent with the BRCA1 syndrome was found in four (1.1%) probands, all below age 50 years, while for BRCA2 there were five (1.4%) probands, three below age 50 years and two 50 years or older. Site-specific familial breast cancer was found in 23 (6.4%) probands. Population-based multiple-case breast cancer families can rapidly be identified through CR. These families can make substantial contributions to the study of genetic and environmental etiology of the disease as well as benefit from preventive and therapeutic efforts. As new knowledge and tools in molecular genetics become available, there is an urgent need for large population-based registries of families at high risk for cancer.
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PMID:Validation of family history of breast cancer and identification of the BRCA1 and other syndromes using a population-based cancer registry. 872 46

Breast cancer is the most common cancer in women, accounting for 32% of all newly diagnosed cancers. Demographic characteristics associated with an increased risk include increasing age, birth in North America or northern Europe, high socioeconomic status, never having been married, and, for breast cancer diagnosed after 45 years of age, the white race. Early age at menarche, late age at menopause, late age at first full-term pregnancy, and low parity increase risk, while removal of the ovaries at an early age is protective. Obesity increases risk in postmenopausal women. Having a first degree relative with breast cancer confers an increased risk, especially if both a mother and a sister have had breast cancer at an early age. Mutations in the BRCA1 and BRCA2 genes are associated with an inherited susceptibility to breast cancer at an early age. Other markers of increased risk include atypical and hyperplastic epithelial cells in nipple aspirate fluid, nodular densities on mammogram, and biopsy-confirmed benign proliferative breast disease. Little can be done at present to reduce breast cancer risk through primary prevention, but secondary prevention by mammographic screening in women of age 50 and older reduces mortality from breast cancer.
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PMID:Epidemiology and prevention of breast cancer. 872 15

The common hereditary forms of breast cancer have been largely attributed to the inheritance of mutations in the BRCA1 or BRCA2 genes. However, it is not yet clear what proportion of hereditary breast cancer is explained by BRCA1 and BRCA2 or by some other unidentified susceptibility gene(s). We describe the proportion of hereditary breast cancer explained by BRCA1 or BRCA2 in a sample of North American hereditary breast cancers and assess the evidence for additional susceptibility genes that may confer hereditary breast or ovarian cancer risk. Twenty-three families were identified through two high-risk breast cancer research programs. Genetic analysis was undertaken to establish linkage between the breast or ovarian cancer cases and markers on chromosomes 17q (BRCA1) and 13q (BRCA2). Mutation analysis in the BRCA1 and BRCA2 genes was also undertaken in all families. The pattern of hereditary cancer in 14 (61%) of the 23 families studied was attributed to BRCA1 by a combination of linkage and mutation analyses. No families were attributed to BRCA2. Five families (22%) provided evidence against linkage to both BRCA1 and BRCA2. No BRCA1 or BRCA2 mutations were detected in these five families. The BRCA1 or BRCA2 status of four families (17%) could not be determined. BRCA1 and BRCA2 probably explain the majority of hereditary breast cancer that exists in the North American population. However, one or more additional genes may yet be found that explain some proportion of hereditary breast cancer.
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PMID:Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. 875 55

Recent studies have identified mutations in the breast and (ovarian cancer susceptibility gene 2 (BRCA2), one which has been found in the germline of several males and one female affected with breast cancer. To establish the carrier frequency of this mutation in a large population of individuals affected with cancer, we evaluated constitutional DNA isolated from 83 individuals diagnosed with breast cancer and 93 diagnosed with ovarian cancer at any age, 42 of whom reported a family history of cancer. Using a simple allele-specific PCR-based nonradioactive method, we detected a total of eight individuals (4.5%) carrying a 1-bp deletion at nucleotide 6174 of the BRCA2 gene (6174delT). The age of disease onset in the mutant allele carriers was highly variable and typically late onset (41-72 years for breast cancer and 48-73 years for ovarian cancer). Evaluation of family histories for the eight mutant allele carriers revealed that several individuals had significant cancer histories that included, in addition to breast and/or ovarian cancer, an increased incidence of colon, esophageal, pancreatic, stomach, and hematopoietic cancers. Interestingly, seven of the eight individuals were of Ashkenazi Jewish descent. Haplotype data for the mutant allele carriers using markers spanning the region of the BRCA2 gene on chromosome 13ql2-ql3 suggest that only two of the confirmed Jewish Ashkenazi individuals share a single common ancestry, indicating several independent origins for this mutation. These data provide evidence for the presence of a specific BRCA2 mutation which has its origins in both Jewish Ashkenazi and non-Jewish populations. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually help contribute to the development of inexpensive and routine tests such as the one described in our study.
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PMID:A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals. 875 3

Tremendous progress has been made in recent years in understanding the genetic basis of breast cancer. Epidemiological models have been devised which allow risk estimation for women with one or two relatives with breast cancer. The existence of two autosomal dominant breast cancer susceptibility genes (BRCA1 and BRCA2) have been documented. BRCA1 has been isolated and we are beginning to catalog BRCA1 mutations which appear to be etiologically related to the development of breast cancer in certain families. These BRCA1 mutation studies and the isolation of BRCA2 will allow development of accurate DNA-based testing for the prediction of individual risk in women with a family history of breast cancer. Work by several groups is progressing rapidly on the isolation BRCA2. Ongoing studies investigating the function of BRCA1, and eventually BRCA2, will lead to a better understanding of the role these important genes normally play in preventing the development of breast cancer. Finally, additional breast cancer susceptibility genes are likely to be identified, further expanding the number of tools we have to study, and eventually prevent, breast cancer.
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PMID:Familial breast cancer. 878 76


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