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61.
Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases 总被引:1,自引:1,他引:0
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Huijts PE Vreeswijk MP Kroeze-Jansema KH Jacobi CE Seynaeve C Krol-Warmerdam EM Wijers-Koster PM Blom JC Pooley KA Klijn JG Tollenaar RA Devilee P van Asperen CJ 《Breast cancer research : BCR》2007,9(6):R78-9
Introduction
Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.Methods
We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.Results
Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.Conclusion
Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles. 相似文献62.
Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study
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Annegien Broeks Linde M Braaf Angelina Huseinovic Anke Nooijen Jos Urbanus Frans BL Hogervorst Marjanka K Schmidt Jan GM Klijn Nicola S Russell Flora E Van Leeuwen Laura J Van 't Veer 《Breast cancer research : BCR》2007,9(2):1-9
Introduction
Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice. We sought to reproduce this MPA cancer model in C57BL/6 mice because of their widespread use in genetic engineering. Within this experimental setting, we studied the carcinogenic effects of MPA, the morphologic changes in mammary glands that are induced by MPA and progesterone, and the levels of ER and PR expression in MPA-treated and progesterone-treated mammary glands. Finally, we evaluated whether the differences found between BALB/c and C57BL/6 mouse strains were due to intrinsic differences in epithelial cells.Methods
The carcinogenic effect of MPA was evaluated in C57BL/6 mice using protocols proven to be carcinogenic in BALB/c mice. In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR. Hormone levels were determined by radioimmunoassay. Isolated mammary epithelial cells were transplanted into cleared fat pads of 21-day-old female Swiss nu/nu mice or control congenic animals.Results
MPA failed to induce mammary carcinomas or significant morphologic changes in the mammary glands of C57BL/6 mice. The expression of ER-α and PR isoform A in virgin mice was surprisingly much higher in BALB/c than in C57BL/6 mammary glands, and both receptors were downregulated in progestin-treated BALB/c mice (P < 0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ER-β expression followed a similar trend. No differences in hormone levels were found between strains. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice abolished the mammary gland morphologic differences and the ER and PR differences between strains.Conclusion
C57BL/6 mammary glands are resistant to MPA-induced carcinogenesis and to hormone action. MPA and progesterone have different effects on mammary glands. Low ER-α and PR-A levels in untreated mammary glands may be associated with a low-risk breast cancer profile. Although we cannot at this time rule out the participation of other, untested factors, our findings implicate the stroma as playing a crucial role in the strain-specific differential hormone receptor expression and hormone responsiveness. 相似文献63.
64.
Richter GM; Noeldge G; Palmaz JC; Roessle M; Slegerstetter V; Franke M; Gerok W; Wenz W; Farthman E 《Radiology》1990,174(3):1027
65.
Dachman AH; Lieberman J; Osnis RB; Chen SY; Hoffmann KR; Chen CT; Newmark GM; McGill J 《Radiology》1997,203(2):427
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