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Wilkening S Bermejo JL Burwinkel B Klaes R Bartram CR Meindl A Bugert P Schmutzler RK Wappenschmidt B Untch M Hemminki K Försti A 《Cancer research》2006,66(2):646-648
The mouse double minute 2 (MDM2) oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumor suppressor protein. Further, MDM2 overexpression can inhibit DNA double-strand break repair in a p53-independent manner. Recently, it was shown that a single nucleotide polymorphism (SNP) in the MDM2 promoter was associated with an accelerated tumor formation in individuals with a p53 mutation. The present case-control study investigated the association of this SNP (IVS1+309) with the risk and the age of onset of familial breast cancer in patients with unknown p53 mutation status. Data from 549 women affected by familial breast cancer and 1,065 healthy controls were analyzed. The cases did not carry BRCA1/2 mutations. Cases and controls showed a similar genotype distribution and the SNP did not seem to modify the age of onset of familial breast cancer. The data were also examined taking into account the presence of any additional cancer after breast cancer and the family history of cases; however, no association was found. These results suggest that the SNP IVS1+309 alone affects neither the risk nor the age of onset of heritable breast cancer. 相似文献
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Vaclavicek A Hemminki K Bartram CR Wagner K Wappenschmidt B Meindl A Schmutzler RK Klaes R Untch M Burwinkel B Försti A 《The Journal of clinical endocrinology and metabolism》2006,91(4):1513-1519
CONTEXT: The contribution of prolactin (PRL) through its receptor (PRLR) to the pathogenesis and progression of human mammary tumors has received recent attention. OBJECTIVE: We investigated whether genetic variation in the PRL and PRLR genes is associated with the risk of breast cancer (BC). DESIGN: We conducted a case-control study with a total of seven single nucleotide polymorphisms (SNPs). SETTING: The study was conducted at an academic research laboratory and university clinics. PATIENTS AND OTHER PARTICIPANTS: A total of 441 German familial, unrelated BC cases and 552 controls matched by age, ethnicity, and geographical region participated in the study. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURES(S): SNP genotype and haplotype distributions and haplotype interactions were correlated with the risk of BC. RESULTS: Two SNPs (rs1341239 and rs12210179) within the PRL promoter regions were significantly associated with increased risk in homozygotes for the variant alleles [odds ratio (OR), 1.67 and 95% confidence interval (CI), 1.11-2.50; and OR, 2.09 and 95% CI, 1.23-3.52, respectively]. The PRL haplotype containing the variant alleles of the promoter SNPs increased significantly the risk of BC (OR 1.42, 95%CI 1.07-1.90). A PRLR haplotype was associated with a significant decrease in BC risk (OR 0.69, 95% CI 0.54-0.89). An increasing number of PRL and PRLR risk haplotypes led to a significant trend of increasing risk for BC (chi(2) = 12.15; P = 0.007). CONCLUSIONS: Genetic variation in the PRL and PRLR genes was shown to influence BC risk. Additional studies are needed to further clarify the role of the PRL and PRLR genes in the risk of BC. 相似文献
137.
Engert S Wappenschmidt B Betz B Kast K Kutsche M Hellebrand H Goecke TO Kiechle M Niederacher D Schmutzler RK Meindl A 《Human mutation》2008,29(7):948-958
We present a comprehensive analysis of 1,506 German families for large genomic rearrangements (LGRs) in the BRCA1 gene and of 450 families in the BRCA2 gene by the multiplex ligation-dependent probe amplification (MLPA) technique. A total of 32 pathogenic rearrangements in the BRCA1 gene were found, accounting for 1.6% of all mutations, but for 9.6% of all BRCA1 mutations identified in a total of 1,996 families, including 490 with small pathogenic BRCA1/2 mutations. Considering only high risk groups for hereditary breast/ovarian cancer, the prevalence of rearrangements is 2.1%. Interestingly, deletions involving exon 17 of the BRCA1 gene seem to be most frequent in Germany. Apart from recurrent aberrations like del ex17, dupl ex13, and del ex22, accounting for more than 50% of all BRCA1 LGRs, we could fully characterize 11 novel deletions. Moreover, one novel deletion involving exons 1-7 and one deletion affecting the entire BRCA1 gene were identified. All rearrangements were detected in families with: 1) at least two breast cancer cases prior to the age of 51 years; 2) breast and ovarian cancer cases; 3) ovarian cancer only families with at least two ovarian cancer cases; or 4) a single breast cancer case prior to the age of 36 years, while no mutations were detected in breast cancer only families with no or only one breast cancer case prior to the age of 51 years. Analysis for gross rearrangements in 412 high-risk individuals, revealed no event in the BRCA2 gene and only two known CHEK2 mutations. However, in an additional 38 high-risk families with cooccurrence of female breast/ovarian and male breast cancer, one rearrangement in the BRCA2 gene was found. In summary, we advise restricting BRCA1 MLPA screening to those subgroups that revealed LGRs and recommend BRCA2 MLPA screening only for families presenting with cooccurrence of female and male breast cancer. 相似文献
138.
Pankaj Talwar VSM RK Sharma VSM K Sandeep Shashi Sareen BS Duggal 《Medical Journal Armed Forces India》2011,67(3):241-244
Background
The transvaginal ultrasound-guided embryo reduction technique is a feasible option for the prevention and management of the medical and obstetric risks associated with high-order multiple pregnancy resulting from assisted reproductive treatment.Method
Multifoetal pregnancy reduction was carried out in 51 in vitro fertilisation pregnancies (IVF) and one intrauterine quintuplet pregnancy resulting from intrauterine insemination (IUI) using transvaginal approach under ultrasonographic guidance.Results
Of the 52 embryo reduction procedures, 48 (92%) were performed between the seventh and eighth weeks of gestation, three between eighth and ninth weeks and one in the 10th week of gestation. Forty-nine patients (94%) underwent reduction from triplets to twins, two from quadruplet to twins, and one from quintuplet to twin pregnancy. The average time required for the embryo reduction was 5.0±0.5 minutes per sac in early gestation (6th-9th weeks), increasing to 8.5 minutes per sac for later procedures, due to technical difficulties brought about by increased embryo size and mobility. All embryo reduction procedures were successfully performed in a single session.Conclusion
Transvaginal ultrasound guided embryo reduction technique performed between seventh and eighth-weeks of gestation is an effective and safe procedure for embryo reduction. 相似文献139.
Chen Du Dorothea Mark Barbara Wappenschmidt Beatrix Böckmann Brigitte Pabst Saki Chan Han Cao Susanne Morlot Caroline Scholz Bernd Auber Kerstin Rhiem Rita Schmutzler Thomas Illig Brigitte Schlegelberger Doris Steinemann 《Breast cancer research and treatment》2018,169(3):561-571
Background
Physical activity is inversely associated with the risk of breast cancer among women in the general population. It is not clear whether or not physical activity is associated with the risk of BRCA-associated breast cancer.Methods
We conducted a case–control study of 443 matched pairs of BRCA mutation carriers to evaluate the association between physical activity and breast cancer risk. Moderate and vigorous physical activities at ages 12–13, ages 14–17, ages 18–22, ages 23–29 and ages 30–34 were determined using the Nurses’ Health Study II Physical Activity Questionnaire. We estimated mean metabolic equivalent task hours/week for moderate, vigorous and total physical activities overall (ages 12–34), during adolescence (ages 12–17) and during early adulthood (ages 18–34). Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for total, moderate and strenuous recreational physical activities and breast cancer risk, by menopausal status.Results
Overall, there was no significant association between total physical activity and subsequent breast cancer risk (ORQ4 vs. Q1 = 1.01, 95% CI 0.69–1.47; P-trend = 0.72). Moderate physical activity between ages 12–17 was associated with a 38% decreased risk of premenopausal breast cancer (ORQ4 vs. Q1 = 0.62; 95% CI 0.40–0.96; P-trend = 0.01). We found no association between exercise and breast cancer diagnosed after menopause.Conclusions
These findings suggest that early-life physical activity is associated with a reduced risk of premenopausal breast cancer among BRCA mutation carriers.Impact
Future prospective analyses, complemented by mechanistic evidence, are warranted in this high-risk population.140.
RK SHARMA 《Medical Journal Armed Forces India》1998,54(1):44-46
Neonatal sepsis continues to be a major cause of morbidity and mortality in India. To aid the diagnosis several direct and indirect methods are available. Sepsis screen has resulted in decrease in indiscriminate use of antibiotics. C-reactive protein can be easily estimated and is a useful indicator for favourable outcome or complication. The bacterial flora causing sepsis has changed over the years. Antimicrobial chemotherapy should be based on the prevalent organisms in the neonatal ICU. Outcome can be improved by judicious use of newer antibiotics and exchange transfusion when indicated.KEYWORDS: Antibiotics, Meningitis, Neonatal sepsis 相似文献