Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight breast cancer pedigrees with a high probability of containing individuals with the BRCA1 gene mutation (odds 79.2-99.9 per cent) were identified through genetic linkage analysis using probes located within q12-22 on the long arm of chromosome 17. Some 102 female relatives were successfully typed with one or both of adjacent markers D17S588 and D17S579, and 41 were probable non-BRCA1 mutation carriers. Of the remaining 61 women classified as probable BRCA1 carriers, breast cancer was diagnosed in 35. As expected from epidemiological segregation analysis studies, 13 of these had bilateral disease. Approximately two-thirds of women unaffected by malignancy and alive at the time of observation were non-BRCA1 carriers. Lifetime disease penetrance of the BRCA1 gene was 88 per cent and this plateau was reached earlier (by age 65 years) than that estimated in segregation analysis. The survival curve of patients with breast cancer was less steep in BRCA1 gene carriers than that in the general population; 5-, 10- and 20-year survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent respectively. The 5-year survival rate was significantly higher in BRCA1 carriers than that in an age-matched Scottish population (P < 0.05).
 ...
PMID:Breast cancer incidence, penetrance and survival in probable carriers of BRCA1 gene mutation in families linked to BRCA1 on chromosome 17q12-21. 782 Apr 89

The breast-ovary cancer-family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17q12-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of the 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer-family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations.
 ...
PMID:An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium. 782 86

Dominant predisposition to early-onset breast cancer and/or ovarian cancer in many families is known to be the result of germ-line mutations in a gene on chromosome 17q, known as BRCA1. In this paper we use data from families with evidence of linkage to BRCA1 to estimate the age-specific risks of breast and ovarian cancer in BRCA1-mutation carriers and to examine the variation in risk between and within families. Under the assumption of no heterogeneity of risk between families, BRCA1 is estimated to confer a breast cancer risk of 54% by age 60 years (95% confidence interval [CI] 27%-71%) and an ovarian cancer risk of 30% by age 60 years (95% CI 8%-47%). Similar lifetime-risk estimates are obtained by examining the risks of contralateral breast cancer and of ovarian cancer, in breast cancer cases in linked families. However, there is significant evidence of heterogeneity of risk between families; a much better fit to the data is obtained by assuming two BRCA1 alleles, one conferring a breast cancer risk of 62% and an ovarian cancer risk of 11% by age 60 years, the other conferring a breast cancer risk of 39% and an ovarian cancer risk of 42%, with the first allele representing 71% of all mutations (95% CI 55%-87%). There is no evidence of clustering of breast and ovarian cancer cases within families.
 ...
PMID:Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. 782 87

The VH1-related human protein (VHR) gene was localized to human chromosome 17q21 in a region thought to contain the BRCA1 locus, a locus that confers susceptibility to breast and ovarian cancer. VHR encodes a phosphatase with dual specificity for tyrosine and serine residues. Thus it is a plausible candidate for a tumor suppressor gene such as BRCA1. To test this possibility, the VHR coding sequence was screened in individuals with familial breast cancer and in sporadic breast tumor and breast cancer cell lines. No mutations were detected, suggesting that the VHR gene is not BRCA1.
 ...
PMID:Localization of the VHR phosphatase gene and its analysis as a candidate for BRCA1. 782 67

EDH17B2, the gene encoding 17 beta-hydroxysteroid dehydrogenase type 1, has been suggested as a candidate for the familial breast cancer gene, BRCA1, located on 17q12-q21. We analyzed the promoter region of EDH17B2 in DNA from 20 control individuals and 40 patients with familial breast cancer. Two frequent (designated vI and vIII) and two rare (vII and vIV) nucleotide variations were present in both the breast cancer patients and the controls, except the alteration vII, which was found only in one patient. Although the data do not support the identification of EDH17B2 as the BRCA1 gene, it is of interest that point mutation vIV (A-->C) was located in the putative TATA box of the EDH17B2 gene. Reporter gene analyses showed that the mutation vIV decreases EDH17B2 promoter activity by an average of 45% in in vitro assays, suggesting that nucleotide A at position -27 is significant for efficient transcription.
 ...
PMID:A point mutation in the putative TATA box, detected in nondiseased individuals and patients with hereditary breast cancer, decreases promoter activity of the 17 beta-hydroxysteroid dehydrogenase type 1 gene 2 (EDH17B2) in vitro. 782 82

A gene for hereditary breast and ovarian cancer, BRCA1, has been mapped to chromosome 17q12-q21. This gene is responsible for cancer susceptibility in the majority of families with multiple cases of ovarian cancer and early-onset breast cancer. We report linkage results of a family with 10 cases of breast cancer and a single case of ovarian cancer. A recombinant event in this family places BRCA1 distal (telomeric) to the locus EDH17B2, which codes for the enzyme estradiol 17 beta-dehydrogenase II. This recombinant is based on the appearance of breast cancer in a 45 year old woman. Under our genetic model, we estimate the probability that this woman carries a BRCA1 mutation to be 94%. These data further reduce the region of assignment of BRCA1 on chromosome 17q12-q21 and should expedite positional cloning of this important gene.
 ...
PMID:The gene for hereditary breast-ovarian cancer, BRCA1, maps distal to EDH17B2 in chromosome region 17q12-q21. 783 28

Approximately 20,000 women are diagnosed with ovarian cancer in the United States each year, and some 12,000 women die because of it. Epithelial ovarian cancer, the most common histopathologic type, is uncommon before age 40 years, after which incidence rates increase steeply until age 70-79 years and then decrease somewhat. In the United States, the lifetime risk from birth to age 85 years is about 1.5%. There is general agreement that residence in North America or northern Europe, nulliparity, and having a mother or sister with ovarian cancer are associated with an elevated risk, and that increasing number of pregnancies (whether or not full term), increasing length of oral contraceptive use, and increasing duration of lactation are protective. A history of breast or endometrial cancer appears to be associated with a slight elevation in risk. Apart from oral contraceptive use, none of these characteristics can be modified easily to reduce ovarian cancer risk. However, long-term oral contraceptive use before the menopause could prevent as much as half of all ovarian cancer. At present, the subgroup of the population at highest risk consists of women with a mother or sister with the disease; the lifetime ovarian cancer risk in these women is about 9%. A small fraction of them have families with multiple cases of ovarian cancer and early-onset breast cancer, due largely or entirely to mutated alleles of the gene BRCA1. These women, who have a lifetime risk of breast or ovarian cancer of 85-100%, need aggressive screening and possibly prophylactic surgery.
 ...
PMID:Characteristics relating to ovarian cancer risk: implications for prevention and detection. 863 61

More women in all risk categories are seeking information regarding their individual breast cancer risk, and there is a need for their primary care clinicians to be able to assess familial risk factors for breast cancer, provide individualized risk information, and offer surveillance recommendations. Estimates of the number of women with a family history of breast cancer range from approximately 5% to 20%, depending on the population surveyed. Many of these women will not have a family history that suggests the presence of a highly penetrant breast cancer susceptibility gene. However, a small subset of such women will come from families with a striking incidence of breast and other cancers often associated with inherited mutations. The development and refinement of risk prediction models provide an epidemiologic basis for counseling women with a family history that does not appear related to a dominant susceptibility gene. contrast, the recent isolation of BRCA1, the localization of BRCA2, and the acknowledgement that additional breast cancer susceptibility genes must exist provide a molecular basis for counseling some high-risk women. We present a guide for primary care clinicians that may be helpful in defining families as moderate or high risk, in determining individual risk in women with a family history of breast cancer based on this distinction, and for counseling women in a setting where the data necessary to design surveillance and prevention strategies are lacking. We include criteria for selecting women who may be candidates for detection of inherited mutations in breast cancer susceptibility genes.
 ...
PMID:Assessment and counseling for women with a family history of breast cancer. A guide for clinicians. 783 92

A number of candidate tumor suppressor genes located on the human chromosome 17 are thought to have a role to play in the development of breast cancer. In addition to the p53 gene on 17p13.1 and the BRCA1 gene mapped to 17q12-21, other chromosomal regions for tumor suppressor genes have been suggested to exist on 17p13.3 and both the central and the distal parts of 17q, although definitive functional proof of their involvement in breast cancer tumorigenesis is still lacking. In this report we show that microcell transfer of a human chromosome 17 into wild-type p53 breast cancer cells CAL51 results in loss of tumorigenicity and anchorage-independent growth, changes in cell morphology and a reduction of cell growth rates of the neo-selected microcell hybrids. In the hybrid cells, which express the p53 wild-type protein, only the p- and the distal parts of the q arm of donor chromosome 17 are transferred. Thus, our results provide functional evidence for the presence of one or more tumor suppressor gene(s) on chromosome 17, which are distinct from the p53 and the BRCA1 genes.
 ...
PMID:Suppression of tumorigenicity of breast cancer cells by transfer of human chromosome 17 does not require transferred BRCA1 and p53 genes. 784 68

It is well documented that breast cancer aggregates in certain families suggesting a genetic etiology for this cancer. Numerous epidemiologic studies have shown that women with a first degree relative (mother, sister) with breast cancer have double the risk of developing this cancer when compared to women in the general population. More recent studies have shown that the magnitude of the risk of developing breast cancer is dependent on the age at diagnosis and the number of relatives affected. Aggregation of breast cancer in families in itself does not clarify the true nature of the underlying factors which could be genetic or due to familial resemblance in other risk factors. Complex segregation analyses of breast cancer families suggest that breast cancer susceptibility is inherited in some families as an autosomal dominant trait. Recently, a breast cancer susceptibility gene, BRCA1, has been mapped to chromosome 17q12-q21 through linkage analyses. BRCA1 appears to play a role in families with a large number of breast cancer cases who have developed breast cancer before the age 45, and/or who have breast and ovarian cancer cases. The risk of cancer for female carriers of the BRCA1 mutation has been estimated to be 87% for breast cancer and 44% for ovarian cancer by the age of 70. BRCA1 seems to play a role in only a proportion of affected families and it is likely that other genes are also involved. In the majority of breast cancer families with two or three cases, BRCA1 appears to play a small role.
 ...
PMID:[The importance of genetic factors for development of breast cancer]. 784 77


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