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1.  New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study 
Journal of Medical Genetics  2016;53(10):655-661.
Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs.
To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC).
Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed.
232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes.
The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.
PMCID: PMC5099175  PMID: 27208206
Clinical genetics; Genetic screening/counselling; Obstetrics and Gynaecology
3.  Health needs assessment for congenital anomalies in middle-income countries: Examining the case for neural tube defects in Brazil 
Journal of Community Genetics  2013;5(2):147-155.
Recent economic improvement in Brazil has been reflected in better maternal–child health indicators, with decreases in infant and perinatal mortality. However, under-five mortality due to congenital disorders remained unchanged, and congenital disorders have become the second leading cause of infant mortality. In the present study, we used the PHG Foundation Health Needs Assessment (HNA) Toolkit with the objective of first assessing the burden of disease caused by neural tube defects (NTDs) in Brazil and the impact of interventions already put in place to address the burden, and second to evaluate and prioritize further interventions and policies required for its prevention and treatment. The results from these two components of the HNA process are described in this paper. The published literature was reviewed to identify studies of NTDs (prevalence; morbidity; prenatal, perinatal, and postnatal mortality; treatment or prevention). Data on indicators of maternal and child health were obtained directly from the Brazilian Ministry of Health, through the online Live Births Information System (SINASC) and from the Mortality Information System (SIM). Descriptive analyses included reports of the rates of NTD in liveborns, fetal, and infant deaths. Differences between folic acid flour pre-fortification (2001–2004) and post-fortification (2006–2010) periods were expressed as prevalence rate ratios. Around 20 % of fetal deaths were related to congenital disorders with approximately 5 % of those being NTDs. For infant mortality, congenital disorders were notified in approximately 15 % of cases, with NTDs present in 10 % of the malformed children. Although statistically significant, the prevalence rate ratio (PRR) for spina bifida in live births was only 0.937 (95 % confidence interval (CI) 0.884–0.994), a decrease of 6.3 % when comparing the pre and post-fortification periods. The impact of fortification seemed to be more visible in fetal deaths due to anencephaly (PRR = 0.727, 95 % CI 0.681–0.777) and for spina bifida (PRR = 0.700, 95 % CI 0.507–0.967) with associated decreases of 27.3 and 30 %. The lower impact of folic acid fortification in Brazil, compared to other Latin-American countries, can be due to differences in dietary habits, concentration of folic acid in flour, as well as characteristic population ethnic composition. The HNA led to the identification of the needs to be addressed in Brazil, including the improvement of reporting congenital disorders within the nationwide birth certification system, and revision of the policy of flour folic acid fortification.
PMCID: PMC3955461  PMID: 23990401
Neural tube defects; Folic acid fortification; Brazil; Health Needs Assessment
4.  The use of a Toolkit for health needs assessment on neural tube defects in Argentina 
Journal of Community Genetics  2012;4(1):77-86.
Health needs assessment (HNA) is a commonly used process for those working in public health. The PHG Foundation has developed a Toolkit to provide users with a stepwise approach for undertaking a HNA on birth defects. We report the findings from using the Toolkit to examine needs in relation to policies and programs, services, and interventions for neural tube defects (NTDs) in Argentina. The trend over the last few decades is one of decline in infant mortality from nutritional and infectious causes, thus further increasing the relative importance of birth defects. The observed prevalence of NTDs is consistent with that reported internationally. Since 2002 folic acid fortification (FAF) has been mandatory by law, and different studies have shown at least a 50 % decrease in the birth prevalence of NTDs after FAF. In Argentina, there is inequity between the public and non-public health sectors. The birth prevalence of NTDs seems lower in the non-public sector, possibly as a result of better nutritional status of women, higher access to folic acid supplementation, and earlier prenatal diagnosis followed by termination of pregnancy (ToP) in non-public hospitals. Although illegal, ToP is believed to be widespread, with better access for people of higher socioeconomic status. Through the process of HNA, we identified several unmet needs regarding registration of cases, public and professional education, legislation, and organization of care pathways. In our experience, the Toolkit brought together people working on the same issue, and it engaged and motivated experts and stakeholders to work together to tackle the problem.
PMCID: PMC3537973  PMID: 23055101
Health needs assessment; Argentina; Neural tube defects; Health services; Interventions
5.  Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis 
BMC Research Notes  2012;5:476.
Cell-free fetal DNA (cffDNA) can be detected in maternal blood during pregnancy, opening the possibility of early non-invasive prenatal diagnosis for a variety of genetic conditions. Since 1997, many studies have examined the accuracy of prenatal fetal sex determination using cffDNA, particularly for pregnancies at risk of an X-linked condition. Here we report a review and meta-analysis of the published literature to evaluate the use of cffDNA for prenatal determination (diagnosis) of fetal sex. We applied a sensitive search of multiple bibliographic databases including PubMed (MEDLINE), EMBASE, the Cochrane library and Web of Science.
Ninety studies, incorporating 9,965 pregnancies and 10,587 fetal sex results met our inclusion criteria. Overall mean sensitivity was 96.6% (95% credible interval 95.2% to 97.7%) and mean specificity was 98.9% (95% CI = 98.1% to 99.4%). These results vary very little with trimester or week of testing, indicating that the performance of the test is reliably high.
Based on this review and meta-analysis we conclude that fetal sex can be determined with a high level of accuracy by analyzing cffDNA. Using cffDNA in prenatal diagnosis to replace or complement existing invasive methods can remove or reduce the risk of miscarriage. Future work should concentrate on the economic and ethical considerations of implementing an early non-invasive test for fetal sex.
PMCID: PMC3444439  PMID: 22937795
Cell-free fetal DNA; Meta-analysis; Non-invasive prenatal diagnosis
6.  The Association Between the Peroxisome Proliferator-Activated Receptor-γ2 (PPARG2) Pro12Ala Gene Variant and Type 2 Diabetes Mellitus: A HuGE Review and Meta-Analysis 
American Journal of Epidemiology  2010;171(6):645-655.
The peroxisome proliferator-activated receptor-γ gene (PPARG) has been implicated in the etiology of type 2 diabetes mellitus and has been investigated in numerous epidemiologic studies. In this Human Genome Epidemiology review, the authors assessed this relation in an updated meta-analysis of 60 association studies. Electronic literature searches were conducted on September 14, 2009. Population-based cohort, case-control, cross-sectional, or genome-wide association studies reporting associations between the PPARG Pro12Ala gene variant (rs1801282) and type 2 diabetes were included. An updated literature-based meta-analysis involving 32,849 type 2 diabetes cases and 47,456 controls in relation to the PPARG Pro12Ala variant was conducted. The combined overall odds ratio, calculated by per-allele genetic model random-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, was 0.86 (95% confidence interval: 0.81, 0.90). The analysis indicated a moderate level of heterogeneity attributable to genuine variation in gene effect size (I2 = 37%). This may reflect the variation observed between ethnic populations and/or differences in body mass index. Work on PPARG Pro12Ala should now focus on the observed heterogeneity in the magnitude of the association between populations. Further investigations into gene-gene and gene-environment interactions may prove enlightening.
PMCID: PMC2834889  PMID: 20179158
diabetes mellitus, type 2; epidemiology; genetics; genome, human; meta-analysis; PPAR gamma; review
7.  Systematic Reviews of Genetic Association Studies 
PLoS Medicine  2009;6(3):e1000028.
Gurdeep S. Sagoo and colleagues describe key components of the methodology for undertaking systematic reviews and meta-analyses of genetic association studies.
PMCID: PMC2650724  PMID: 19260758

Results 1-7 (7)