Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. There is a recent report that BRCA2 carriers with prostate cancer have poorer survival than noncarrier prostate cancer patients. In this study, we compared survival of men with a BRCA2 mutation and prostate cancer with that of men with a BRCA1 mutation and prostate cancer. We obtained the age at diagnosis, age at death or current age from 182 men with prostate cancer from families with a BRCA2 mutation and from 119 men with prostate cancer from families with a BRCA1 mutation. The median survival from diagnosis was 4.0 years for men with a BRCA2 mutation vs 8.0 years for men with a BRCA1 mutation, and the difference was highly significant (Po0.01). It may be important to develop targeted chemotherapies to treat prostate cancer in men with a BRCA2 mutation. British Journal of Cancer (2008) BRCA2 is a multisite cancer gene. It is generally thought that BRCA2 mutations primarily affect women, but men with mutations are also at elevated cancer risk. The two most important cancer sites for males who carry a mutation are the prostate and the pancreas (Liede et al, 2004). The risk of prostate cancer is elevated approximately fivefold in BRCA2 carriers, compared to noncarriers. Genetic counselors and urologists advise men with BRCA2 mutations to undergo surveillance with annual PSA testing from the age of 40 years -a recommendation based on the perceived effectiveness of prostate screening. It is hoped that screening leads to early diagnosis, when cure rates are high. A recent study from Iceland suggests that prostate cancers in men with a BRCA2 mutation may be unusually aggressive (Tryggvadottir et al, 2007). Tryggvadottir et al (2007) identified the Icelandic founder mutation (BRCA2 999 del5) in 30 of the 527 prostate cancer patients studied (5.7%). Men with a BRCA2 mutation had a median survival of only 2.1 years, compared with 12.4 years for noncarriers (Po0.01). The survival difference could not be explained by stage or grade. It is important that these findings be replicated because of the implications for the screening of men with a BRCA2 mutation. We identified the prostate cancer patients in a panel of 2673 families with a BRCA1 or a BRCA2 mutation and estimated survival of the men in the two subgroups. METHODSMen with prostate cancer were included in the survival analysis if they were from a family with a BRCA mutation and if they were (a) known to carry the familial BRCA mutation, or (b) if they were a first-degree relative of a known carrier, or (c) if they were a firstdegree relative of a woman diagnosed with breast or ovarian cancer. For each eligible man with prostate cancer, information was collected on age at diagnosis, age at death (if deceased) or age when last known alive (if alive). Information was collected by the
The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
BMI = body mass index; LRT = likelihood ratio test; SHBG = sex hormone binding globulin; WHR = waist-hip ratio. (Print ISSN 1465-5411; Online ISSN 1465-542X). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any non-commercial purpose, provided this notice is preserved along with the article's original URL. Breast Cancer Research Vol 5 No 2 Adebamowo et al. Research article Waist-hip ratio and breast cancer risk in urbanized Nigerian women AbstractBackground: The aim of the study was to examine the relationship between waist-hip ratio and the risk of breast cancer in an urban Nigerian population. Methods:Between March 1998 and August 2000, we conducted a case-control study of hospital-based breast cancer patients (n = 234) and population-based controls (n = 273) using nurse interviewers in urban Southwestern Nigeria.Results: Multivariable logistic regression showed a significant association between the highest tertile of waist-hip ratio and the risk of breast cancer (odds ratio = 2.67, 95% confidence interval = 1.05-6.80) among postmenopausal women. No association was found in premenopausal women. Conclusion:The present study, the first in an indigenous African population, supports other studies that have shown a positive association between obesity and breast cancer risk among postmenopausal women.Keywords: breast cancer, Nigeria, obesity, waist-hip ratio, women Open AccessAvailable online http://breast-cancer-research.com/content/5/2/R18 R19 diet and physical activity (both contributing to obesity), use of hormones/other medications, and obstetric/gynecological practices [6]. In the current paper, we present the results of the first study of the association between waist-hip ratio (WHR) and breast cancer in an indigenous African population.
Deletions of chromosomal band 9p21 have been detected in various tumor types as well as in more than 20% of acute lymphoblastic leukemia (ALL). These deletions frequently include the entire interferon (IFN) gene cluster as well as the methylthioadenosine phosphorylase (MTAP) gene. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) was proposed as a candidate tumor-suppressor gene on 9p21 because it is frequently deleted in cell lines derived from multiple tumor types. To determine if CDKN2 or another closely related gene on 9p is the target of 9p deletions in ALL and other hematologic malignancies, we analyzed 20 primary patient samples (13 ALL, 2 acute myeloid leukemias [AML], and 5 non-Hodgkin's lymphomas [NHL]) with 9p rearrangements using Southern blot analysis, fluorescence in situ hybridization (FISH), and single- strand conformation polymorphism (SSCP) for alterations of CDKN2. Homozygous deletions of the CDKN2/CDKN2B (p15) region were detected in 10 cases (50%; 6 ALL, 2 AML, and 2 NHL). In 1 additional case, the intensity of the Southern blot band was significantly reduced, suggesting a CDKN2 deletion in a subpopulation of the malignant cells. No CDKN2 or CDKN2B rearrangements were seen. The IFN gene cluster was homozygously deleted in 2 of 15 (13%) analyzed cases, whereas the MTAP gene was deleted in 6 of 15 cases (40%). In addition, hemizygous deletions of the CDKN2 region were identified in 6 ALL cases using interphase FISH. No point mutation of the coding region of CDKN2 was detected by SSCP in these cases. We conclude that CDKN2 is the most frequently homozygously deleted marker on 9p. The absence of point mutations in the coding region of CDKN2 in cases with hemizygous 9p deletions and the frequent codeletion of MTAP, CDKN2B, and other yet unidentified neighboring genes suggest that the simultaneous deletion of these genes may be necessary for the selective growth advantage of malignant cells.
1522 Background: The quality of life (QOL) and psychological impact of incorporating MRI into breast cancer screening programs for high-risk women (HRW) has not been well studied. Psychological and biological risk factors, e.g. cancer history, BRCA mutation, imaging recall, generalized anxiety or clinical depression may mediate QOL outcomes. Methods: 100 HRW undergoing intensive surveillance including yearly mammography, semiannual breast ultrasound and breast MRI have completed QOL (SF-36), anxiety (STAI) and depression (Beck) questionnaires at semi-annual visits. 56 HRW have completed 3 screenings. Differences in QOL measures over time were evaluated using longitudinal regression models. Differences between participants and population norms (PN), women with/without a history of cancer and with/without a BRCA mutation were assessed using t-tests. Results: QOL scores increased over time and were statistically significant for the general health (GH) subscale (p=0.016). All QOL subscales were higher than PN at baseline and were significantly higher than PN at 12 months. Mean GH score at 12 months = 80.0, PN 72.7 (SD14.2, p<0.01). Mean mental health score at 12 months = 78.9, PN 73.4 (SD14.9, p<0.01). At baseline, BRCA carriers had lower QOL scores than non-carriers and women with a history of cancer had higher QOL scores than unaffected participants, although these differences were not statistically significant. Conclusions: These data suggest that intensive breast cancer screening incorporating breast MRI may have a positive effect among HRW. Continued enrollment will allow for multi-variate characterization of psychological and biological predictors of change in QOL and psychological well-being among high-risk women undergoing intensive screening. No significant financial relationships to disclose.
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