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- Hedenfalk, I, et al.
(författare)
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Gene-expression profiles in hereditary breast cancer
- 2001
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 344:8, s. 48-539
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles.METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype.RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations.CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.
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| 3. |
- Narod, S A, et al.
(författare)
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Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group
- 1998
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 339:7, s. 8-424
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women with mutations in either the BRCA1 or the BRCA2 gene have a high lifetime risk of ovarian cancer. Oral contraceptives protect against ovarian cancer in general, but it is not known whether they also protect against hereditary forms of ovarian cancer.METHODS: We enrolled 207 women with hereditary ovarian cancer and 161 of their sisters as controls in a case-control study. All the patients carried a pathogenic mutation in either BRCA1 (179 women) or BRCA2 (28 women). The control women were enrolled regardless of whether or not they had either mutation. Lifetime histories of oral-contraceptive use were obtained by interview or by written questionnaire and were compared between patients and control women, after adjustment for year of birth and parity.RESULTS: The adjusted odds ratio for ovarian cancer associated with any past use of oral contraceptives was 0.5 (95 percent confidence interval, 0.3 to 0.8). The risk decreased with increasing duration of use (P for trend, <0.001); use for six or more years was associated with a 60 percent reduction in risk. Oral-contraceptive use protected against ovarian cancer both for carriers of the BRCA1 mutation (odds ratio, 0.5; 95 percent confidence interval, 0.3 to 0.9) and for carriers of the BRCA2 mutation (odds ratio, 0.4; 95 percent confidence interval, 0.2 to 1.1).CONCLUSIONS: Oral-contraceptive use may reduce the risk of ovarian cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene.
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- Olsson, Håkan, et al.
(författare)
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Sex Ratio in Offspring of Patients with Non-Hodgkin Lymphoma
- 1982
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 306:6, s. 367-368
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Tidskriftsartikel (refereegranskat)abstract
- To the Editor: In a letter in the November 5 issue, Alperovitch and Feingold reported an increased sex ratio (male:female) among children of women with multiple sclerosis.1 We have observed a remarkably decreased sex ratio in the offspring of young adults with non-Hodgkin lymphoma. We recorded the sex of the children of 197 patients with this disease who were participating in an epidemiologic study and obtained the same information from a control group of 240 patients without any evident malignant disease. Interviewing the control patients established that they had mainly cardiovascular or respiratory disorders. The results of this study are. © 1982, Massachusetts Medical Society. All rights reserved.
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| 5. |
- Ranstam, Jonas, et al.
(författare)
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Oral-Contraceptive Use and the Risk of Breast Cancer
- 1987
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 316:3, s. 162-164
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Tidskriftsartikel (refereegranskat)abstract
- To the Editor: The study on oral-contraceptive use and the risk of breast cancer from the Centers for Disease Control (CDC) and the National Institute of Child Health and Human Development (Aug. 14 issue)1 seems to be reassuring for oral-contraceptive users. But, as stated in the editorial by Shapiro in the same issue,2 there are some weak points that need further elucidation. We have found a highly increased risk of breast cancer among young (teenage) oral-contraceptive users in southern Sweden.3 From incidence figures for Sweden, an increase in premenopausal breast cancer can be seen to have started in about 1975,…
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- Sigurdsson, H, et al.
(författare)
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Indicators of prognosis in node-negative breast cancer
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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