BRCA1, a well-known tumor suppressor with multiple interacting partners, is predicted to have diverse biological functions. However, so far its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low-penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate-risk variant, and found that it does not impair DNA damage repair but abrogates the repression of microRNA-155 (miR-155), a bona fide oncomir. Mechanistically, we found that BRCA1 epigenetically represses miR-155 expression via its association with HDAC2, which deacetylates histones H2A and H3 on the miR-155 promoter. We show that overexpression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Our findings demonstrate a new mode of tumor suppression by BRCA1 and suggest that miR-155 is a potential therapeutic target for BRCA1-deficient tumors.

Background Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, while the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Methods Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the NCI-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this pre-planned analysis. Due to the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points based on the 98th percentile. Results The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. Conclusions To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (~ 50 for premenopausal women, 40 for premenopausal on OC, 35 for postmenopausal women).

Background: A positive family history is a known risk factor for several cancers; thus, obtaining a thorough family cancer history is essential in cancer risk evaluation and prevention management. Methods: The Family Health Study, a telephone survey in Connecticut, was conducted in 2001. A total of 1,019 participants with demographic information and family cancer history were included in this study. Prevalence of a positive family history of breast, colorectal, prostate, and lung cancer for first- and second-degree relatives was estimated. Logistic regression was used to compare prevalence by demographic factors. Results: A positive family history among first-degree relatives was reported by 10.9% (95% Confidence Interval, CI = 8.8–13.3) of respondents for breast cancer, 5.1% (95% CI = 3.9–6.7) for colorectal cancer, 7.0% (95% CI = 5.2–9.4) for prostate cancer, and 6.4% (95% CI = 4.9–8.3) for lung cancer. The reported prevalence of family history of specific cancers varied by sex, age and race/ethnicity of the respondents. Conclusion: Family history prevalence for 4 of the most common adult solid tumors is substantial and the reported prevalence varied by respondent characteristics. Additional studies are needed to evaluate tools to promote accurate reporting of family history of cancer.

Background: Although family history of cancer is widely ascertained in research and clinical care, little is known about assessment methods, accuracy, or other quality measures. Given its widespread use in cancer screening and surveillance, better information is needed about the clarity and accuracy of family history information reported in the general population.Methods: This telephone survey in Connecticut examined coherence and completeness of reports from 1,019 respondents about 20,504 biological relatives.Results: Of 2,657 cancer reports, 97.7% were judged consistent with malignancy (versus benign or indeterminate conditions); 79% were site specific, 10.1% had unspecified cancer sites, and 8.6% had "ill-defined" sites. Only 6.1% of relatives had unknown histories. Unknown histories and ambiguous sites were significantly higher for second-degree relatives. The adjusted percentage of first-degree relative reports with ambiguous sites increased with decreasing education and African-American race of survey respondents, and with deceased vital status of relatives. Ambiguous second-degree relative reports were also associated with deceased vital status and with male gender of respondents.Conclusions: These findings suggest that family history of cancer reports from the general population are generally complete and coherent.Impact: Strategies are needed to improve site specificity and thus maximize the utility of such information in primary care settings. Cancer Epidemiol Biomarkers Prev; 19(3); 799-810. ©2010 AACR.

The sequences of the entire blue opsin gene in the squirrel monkey (Saimiri boliviensis) and the five introns of the human blue opsin gene were obtained. Intron 3 of these genes contains an Alu sequence and intron 4 contains a partial mer13 sequence. A comparison of the squirrel monkey opsin sequence with published mammalian opsin sequences shows that features believed to be functionally critical are all conserved. However, the blue opsin has evolved twice as fast as rhodopsin and is only as conservative as the beta globin, which has evolved at the average rate of mammalian proteins. Interestingly, the interhelical loops are, on average, actually more conservative than the transmembrane alpha helical regions. The introns of the blue opsin gene have evolved at the average rate of introns in primate genes.

Although the magnitude of TT is high, the problem of TCO seems to be less serious. The goal of eliminating blinding trachoma from the study area by 2010 represents a big challenge. Based on these survey estimates, the national program could plan resources for the 'S' strategy of trachoma control (surgery for those at immediate risk of blindness).

Introduction:Global funding for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) responses in low-and middle-income countries is decreasing, and becomes unpredictable in the future due to co-existing pandemic of COVID-19. Therefore, lessons learned from a developing country that successfully shifted HIV/AIDS programs to insurance-based systems are in need. Aim of the study was to identify the barriers to enrollment and the use of health insurance (HI) for antiretroviral therapy (ART) in Vietnam. Material and methods:This study is a narrative literature assessment of peer-reviewed publications on HI for accessing ART in Vietnam. Conceptual framework was developed based on the study's objectives with related factors analyzed from user's perspective, provider's perspective, and socioeconomic and cultural factors considered.Results: From user's perspective, the barriers to HI enrollment and the use of HI included awareness of the benefits from HI, affordability for enrollment into HI, fear of stigma and discrimination, fear of responsibility to pay for co-payment, and pre-conception of services provided by HI. From provider's perspective, the barriers were health workers' attitudes, quality of care and treatment services as well as inconsistent and insufficient guidance on social health insurance coverage of care and treatment for people living with HIV (PLHIV). Conclusions:A comprehensive information package on HI and the benefits of HIV/AIDS services integrated into HIV programs should be considered to improve the enrollment into and the use of HI among PLHIV. Additionally, it is very important to encourage the government and local authorities to secure adequate funds for co-payment of ART.

Rare germline mutations in the breast and ovarian cancer predisposition genes BRCA1 and BRCA2 are present in roughly 5 percent of ovarian cancer patients. Both genes play key roles in DNA damage repair but appear to have distinct, although often complementary, functions. The risks of breast and ovarian cancer have been shown to differ between BRCA1 and BRCA2 carriers, and mutation-specific effects have also been suggested for both groups. Published reports comparing the survival of ovarian cancer patients with and without BRCA1/2 mutations generally show a survival advantage among mutation carriers. This is thought to be related to an improved response of carriers to platinum-based therapies. Since it is not known whether BRCA1 and BRCA2 carriers show similar survival patterns, we have performed a large, multicenter study to investigate the impact of germline BRCA1 and BRCA2 mutations on ovarian cancer survival. 3,531 invasive epithelial ovarian cancer cases (1,178 BRCA1, 367 BRCA2 and 1,986 BRCA-negative) with survival time data from twenty-four studies in the U.S.A, Europe, Israel and Asia were included. In our main analysis, we excluded patients who were known or who were likely to have not received platinum-based therapy. Compared to non-carriers, BRCA1 and BRCA2 carriers were more likely to present with advanced stage (BRCA1; p=2×10−4, BRCA2; p=4×10−6), high grade (BRCA1; p=4×10−9, BRCA2; p=1×10−4), serous disease (BRCA1; p=3×10−6, BRCA2; p=0.003). BRCA1 carriers were younger at diagnosis (p=2×10−9) and BRCA2 slightly older at diagnosis (p=0.002) than non-carriers. BRCA1 and BRCA2 carriers did not differ in terms of tumor stage, grade or histology but did show differences in the age at diagnosis (p=2×10−14). In an unadjusted analysis, neither BRCA1 nor BRCA2 carriers differed from non-carriers in overall survival (BRCA1: HR=1.02, p=0.77, BRCA2: HR=0.89, p=0.36). After adjusting for stage, grade, histology and age at diagnosis, BRCA1 carriers showed a modest, non-significant, survival advantage (HR=0.84, p=0.12) while BRCA2 carriers showed a marked improvement (HR=0.57, p=6×10−4) compared to non-carriers. This survival advantage was also seen when comparing BRCA2 carriers to BRCA1 carriers after adjustment for age at diagnosis (HR=0.69, p=5×10−4). Similar results were obtained when we restricted the analysis to high grade, advanced stage, serous cases. The survival differences we observed between BRCA1 and BRCA2 carriers could be related to differences in tumor biology or chemo-sensitivity. Additional analyses investigating the later will be presented in addition to mutation-specific effects within BRCA1 and BRCA2. In this study, we provide strong evidence for genetic heterogeneity of survival effects in ovarian cancer patients with BRCA mutations. This could be applied to both clinical prediction and to aid our understanding of the complex biology of BRCA mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2752. doi:10.1158/1538-7445.AM2011-2752