Usha Menon

The Ohio State University, Columbus, Ohio, United States

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Publications (288)1671.47 Total impact

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    ABSTRACT: Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality. Participants resident in England who had completed both baseline (Wave 1) and follow up (Wave 2) questionnaires were included. Follow-up was through the Health and Social Care Information Centre with deaths censored on 31st December 2012. IMD, education and a range of covariates were explored. Cox regression models adjusted for all covariates were used. Sensitivity analysis using imputation was performed (1) including those with missing data and (2) on the entire cohort who had completed the baseline questionnaire. Of the 54,539 women resident in England who completed both Wave 1 and Wave 2 questionnaires, 4,510 had missing data. The remaining 50,029 women were included in the primary analysis. Area-level IMD was positively associated with all-cause mortality for the most deprived group compared to the least deprived (HR=1.42, CI=1.14-1.78) after adjusting for all potential confounders. Sensitivity analyses showed similar results with stronger associations in the entire cohort (HR=1.90, CI=1.68-2.16). The less educated an individual, the higher the mortality risk (test for trend p=<0.001). However, the crude effect on mortality of having no formal education compared to college/university education disappeared when adjusted for IMD rank (HR=1.08, CI=0.93-1.26). Women living in more deprived areas continue to have higher mortality even in this less deprived cohort and after adjustment for a range of potential confounders. Trial Registration This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978.
    BMC Public Health 12/2015; 15(1). DOI:10.1186/s12889-015-1609-5 · 2.26 Impact Factor
  • Huong D Meeks · Honglin Song · Kyriaki Michailidou · Manjeet K Bolla · Joe Dennis · Qin Wang · Daniel Barrowdale · Debra Frost · Lesley McGuffog · Steve Ellis · [...] · Andrew Berchuck · Anthony Swerdlow · Georgia Chenevix-Trench · Alison M Dunning · Paul D P Pharoah · Per Hall · Douglas F Easton · Fergus J Couch · Amanda B Spurdle · David E Goldgar ·
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    ABSTRACT: Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.
    Journal of the National Cancer Institute 11/2015; 108(2). DOI:10.1093/jnci/djv315 · 12.58 Impact Factor
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    ABSTRACT: Purpose: Identification of serum biomarkers enabling earlier diagnosis of pancreatic ductal adenocarcinoma (PDAC) could improve outcome. Serum protein profiles in patients with pre-clinical disease and at diagnosis were investigated. Experimental design: Serum from cases up to 4 years prior to PDAC diagnosis and controls (UKCTOCS,n=174) were studied, alongside samples from patients diagnosed with PDAC, chronic pancreatitis, benign biliary disease, type 2 diabetes mellitus and healthy subjects (n=298). iTRAQ enabled comparisons of pooled serum from a test set (n=150). Validation was undertaken using MRM and/or western blotting in all 472 human samples and samples from a KPC mouse model. Results: iTRAQ identified thrombospondin-1 (TSP-1) as reduced preclinically and in diagnosed samples. MRM confirmed significant reduction in levels of TSP-1 up to 24 months prior to diagnosis. A combination of TSP-1 and CA19-9 gave an AUC of 0.86, significantly outperforming both markers alone (0.69 & 0.77 respectively; P<0.01). TSP-1 was also decreased in PDAC patients compared to healthy controls (P<0.05) and patients with benign biliary obstruction (P<0.01). Low levels of TSP-1 correlated with poorer survival, pre-clinically (P<0.05) and at clinical diagnosis (P<0.02). In PDAC patients, reduced TSP-1 levels were more frequently observed in those with confirmed diabetes mellitus (P<0.01). Significantly lower levels were observed in PDAC patients with diabetes compared to individuals with type 2 DM (P=0.01). Conclusions: Circulating TSP-1 levels decrease up to 24 months prior to diagnosis of PDAC and significantly enhance diagnostic performance of CA19-9. The influence of diabetes mellitus on biomarker behaviour should be considered in future studies.
    Clinical Cancer Research 11/2015; DOI:10.1158/1078-0432.CCR-15-0879 · 8.72 Impact Factor

  • Journal of Clinical Oncology 11/2015; DOI:10.1200/JCO.2015.64.1365 · 18.43 Impact Factor
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    ABSTRACT: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, responsible for 13 000 deaths per year in the United States. Risk prediction based on identifying germline mutations in ovarian cancer susceptibility genes could have a clinically significant impact on reducing disease mortality. Next generation sequencing was used to identify germline mutations in the coding regions of four candidate susceptibility genes-BRIP1, BARD1, PALB2 and NBN-in 3236 invasive EOC case patients and 3431 control patients of European origin, and in 2000 unaffected high-risk women from a clinical screening trial of ovarian cancer (UKFOCSS). For each gene, we estimated the prevalence and EOC risks and evaluated associations between germline variant status and clinical and epidemiological risk factor information. All statistical tests were two-sided. We found an increased frequency of deleterious mutations in BRIP1 in case patients (0.9%) and in the UKFOCSS participants (0.6%) compared with control patients (0.09%) (P = 1 x 10(-4) and 8 x 10(-4), respectively), but no differences for BARD1 (P = .39), NBN1 ( P = .61), or PALB2 (P = .08). There was also a difference in the frequency of rare missense variants in BRIP1 between case patients and control patients (P = 5.5 x 10(-4)). The relative risks associated with BRIP1 mutations were 11.22 for invasive EOC (95% confidence interval [CI] = 3.22 to 34.10, P = 1 x 10(-4)) and 14.09 for high-grade serous disease (95% CI = 4.04 to 45.02, P = 2 x 10(-5)). Segregation analysis in families estimated the average relative risks in BRIP1 mutation carriers compared with the general population to be 3.41 (95% CI = 2.12 to 5.54, P = 7×10(-7)). Deleterious germline mutations in BRIP1 are associated with a moderate increase in EOC risk. These data have clinical implications for risk prediction and prevention approaches for ovarian cancer and emphasize the critical need for risk estimates based on very large sample sizes before genes of moderate penetrance have clinical utility in cancer prevention. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Journal of the National Cancer Institute 11/2015; 107(11). DOI:10.1093/jnci/djv214 · 12.58 Impact Factor
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    ABSTRACT: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.
    Nature reviews. Cancer 10/2015; 15(11):668-679. DOI:10.1038/nrc4019 · 37.40 Impact Factor
  • Ranjit Manchanda · Rosa Legood · Leigh Pearce · Usha Menon ·
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    ABSTRACT: Objective: To define risk thresholds for cost-effectiveness of risk-reducing salpingo-oophorectomy(RRSO) for ovarian cancer(OC) prevention in low/intermediate risk postmenopausal women. Methods: A decision-analytic model compares lifetime costs-&-effects of offering 'RRSO' with 'no RRSO' to postmenopausal women ≥50years for different lifetime OC-risk thresholds: 2%, 4%, 5%, 6%, 8% and 10%. Well established data from the literature are used to estimate total costs, effects in terms of Quality-Adjusted-Life-Years(QALYs), cancer incidence, incremental cost-effectiveness ratio(ICER) and impact. Costs are reported at 2012 prices; costs/outcomes discounted at 3.5%. Deterministic/Probabilistic sensitivity analysis(PSA) evaluate model uncertainty. Results: RRSO does not save QALYs and is not cost-effective at the 2% general population lifetime OC-risk. At 4% OC-risk RRSO saves QALYs but is not cost-effective. At risk thresholds ≥5%, RRSO saves more life-years and QALYs and is highly cost-effective. The ICERs for OC-risk levels 5%, 6%, 8% and 10% are £15,247, £9958, £4584, and £1864 respectively. The gain in life-years from RRSO equates to 29.2, 40.1, 62.1 and 80.3days at risk thresholds of 5%, 6%, 8% and 10% respectively. The results are not sensitive to treatment costs of RRSO/OC/cardiovascular events but are sensitive to utility-scores for RRSO. On PSA, 67%, 80%, 84%, 91% and 94% of simulations at risk thresholds of 4%, 5%, 6%, 8% and 10% respectively are cost-effective for RRSO. Conclusion: RRSO is highly cost-effective in postmenopausal women aged >50 with ≥5% lifetime OC-risk and increases life-expectancy by >29.2days. The results could have significant clinical implications given the improvements in risk prediction and falling costs of genotyping.
    Gynecologic Oncology 10/2015; DOI:10.1016/j.ygyno.2015.10.001 · 3.77 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here we evaluated associations between common genetic variants (single nucleotide polymorphisms (SNPs) and indels) in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15,397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r(2) with rs17507066=0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1 x10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72x10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r(2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70 x 10(-8)). These data suggest that common variants at 22q11.2 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
    Carcinogenesis 10/2015; DOI:10.1093/carcin/bgv138 · 5.33 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.
    Genetic Epidemiology 09/2015; DOI:10.1002/gepi.21921 · 2.60 Impact Factor
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    ABSTRACT: Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
    Nature Communications 09/2015; 6:8234. DOI:10.1038/ncomms9234 · 11.47 Impact Factor
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    ABSTRACT: To compare the differences in mammogram completion rates over time between Chinese American women with and without a history of mammogram screening. . Secondary analysis of a randomized, controlled intervention study. . Metropolitan areas of Portland, Oregon. . 300 foreign-born Chinese immigrant women aged 40 years or older. Of these, 83 women (28%) had never had a mammogram. . Participants who had not been screened with a mammogram within the past 12 months were randomized into either an education group or a control (brochure) group. All participants completed a baseline survey, which was administered again at 3, 6, and 12 months. . Mammography history, breast cancer knowledge, perceived risks, susceptibility, benefits, and common and cultural barriers. . Women who had never been screened were less likely to have insurance, a regular healthcare provider, or to have been instructed to have a mammogram. Postintervention in the education group, mammogram completion was not significantly different between those with or without a history of screening (p = 0.52). In the control brochure group, significantly more women with a history of screening had a mammogram (p = 0.03). . Practitioners must be aware of differential effects of education on mammography cancer screening based on women's history of screening. . Print material may not be as effective with women who have never been screened with a mammogram. Targeted approaches based on such understanding has the potential to decrease the breast cancer screening disparity among Chinese immigrant women. .
    Oncology Nursing Forum 09/2015; 42(5):470-478. DOI:10.1188/15.ONF.470-478 · 2.79 Impact Factor
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    ABSTRACT: To identify priority areas of research for the Oncology Nursing Society (ONS) Research Agenda for 2014-2018, consistent with ONS's mission to promote excellence in oncology nursing and quality cancer care. . Review of the literature, 2013 ONS Research Priorities Survey, National Institute of Nursing Research, and the National Cancer Institute research foci. . Multimethod consensus-building approach by content leaders and content experts of the ONS Research Agenda Project Team. . The 2014-2018 Research Agenda Project Team identified eight high-priority research areas. The Research Agenda is a synthesis of the state of the science in cancer and identifies gaps and directions for the conduct and dissemination of research. Oncology nurses can use the agenda to inform clinical practice, develop research proposals, inform policy makers, support interdisciplinary research efforts, and promote scientist and clinician collaborations in targeted patient-centered research. .
    Oncology Nursing Forum 09/2015; 42(5):450-65. DOI:10.1188/15.ONF.450-465 · 2.79 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10-8), rs711830 at 2q31.1 (P = 7.5 × 10-12) and rs688187 at 19q13.2 (P = 6.8 × 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.
    Nature Genetics 08/2015; 47(8):888-897. DOI:10.1038/ng.3336 · 29.35 Impact Factor

  • Clinical Cancer Research 08/2015; 21(16 Supplement):POSTER-CTRL-1213-POSTER-CTRL-1213. DOI:10.1158/1557-3265.OVCASYMP14-POSTER-CTRL-1213 · 8.72 Impact Factor
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    ABSTRACT: The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer. The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis. In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001). These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 08/2015; 33(26). DOI:10.1200/JCO.2015.61.2408 · 18.43 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):2838-2838. DOI:10.1158/1538-7445.AM2015-2838 · 9.33 Impact Factor
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    ABSTRACT: Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3,194 cases and 7,060 controls) and a large ovarian cancer dataset genotyped on the customised iCOGS arrays (10,065 cases and 21,663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI=0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI=0.07-0.89 and 0.40, 95% CI=0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI=0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Human Molecular Genetics 07/2015; 24(20). DOI:10.1093/hmg/ddv306 · 6.39 Impact Factor
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    ABSTRACT: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) aims to establish the efficacy of 2 different ovarian cancer screening schedules. The psychosocial substudy examines the psychological factors associated with the screening program. Women aged 50 to 75 years from 16 UK gynecologic centers randomized to annual multimodal screening or ultrasound screening (US) groups were followed up for 7 years. Psychosocial data from women who withdrew from the study after a repeat screen were examined. Sixteen percent (3499/21,733) of women requiring a repeat screening test in addition to annual screen withdrew from the study: 12.9% (1560/12,073) from the multimodal group and 20.1% (1939/9660) from the US group. An estimated relative risk of withdrawal is 1.46 (95% confidence interval, 1.36-1.56; P ≤ 0.001) for the US arm. High anxiety trait and increased psychological morbidity significantly influenced withdrawal, even when age, screening center, and group were taken into account (P < 0.001). The risk of withdrawal decreased significantly the longer a woman stayed in UKCTOCS, irrespective of the number of screens and intensity in the preceding year. Withdrawal rate was greater in women undergoing US screening and in those who had repeats earlier in UKCTOCS. Having a high predisposition to anxiety, high current state anxiety, and above threshold general psychological morbidity all increased the withdrawal rate.
    International Journal of Gynecological Cancer 07/2015; 25(8). DOI:10.1097/IGC.0000000000000507 · 1.95 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by co-expression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly co-expressed with each selected TF gene in the unified microarray data set of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this data set were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P<0.05 and FDR<0.05). These results were replicated (P<0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific data sets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 07/2015; 24(10). DOI:10.1158/1055-9965.EPI-14-1270 · 4.13 Impact Factor
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    ABSTRACT: Risk-reducing-salpingectomy and Delayed-Oophorectomy (RRSDO) is being proposed as a two-staged approach in place of RRSO to reduce the risks associated with premature menopause in high-risk women. We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO. Baseline characteristics were described using descriptive statistics. A Chi square test was used to compare categorical, Kendal-tau-b test for ordinal and Mann-Whitney test for continuous variables between two groups. 173/708 (24.4 %) of invitees responded. 71 % respondents (CGG = 57 %/BGCS = 83 %, p = 0.005) agreed with the tubal hypothesis for OC, 55 % (CGG = 42 %/BGCS = 66 %, p = 0.003) had heard of RRSDO and 48 % (CGG = 46 %/BGCS = 50 %) felt evidence was not currently strong enough for introduction into clinical practice. However, 60 % respondents' (CGG = 48 %/BGCS = 71 %, p = 0.009) favoured offering RRSDO to high-risk women declining RRSO, 77 % only supported RRSDO within a clinical trial (CGG = 78 %/BGCS = 76 %) and 81 % (CGG = 76 %/BGCS = 86 %) advocated a UK-wide registry. Vasomotor symptoms (72 %), impact on sexual function (63 %), osteoporosis (59 %), hormonal-therapy (55 %) and subfertility (48 %) related to premature menopause influenced their choice of RRSDO. Potential barriers to offering the two-stage procedure included lack of data on precise level of benefit (83 %), increased surgical morbidity (79 %), loss of breast cancer risk reduction associated with oophorectomy (68 %), need for long-term follow-up (61 %) and a proportion not undergoing DO (66 %). There were variations in perception between BGCS/CGG members which are probably attributable to differences in clinical focus/expertise between these two groups. Despite concerns, there is reasonable support amongst UK clinicians to offering RRSDO to premenopausal high-risk women wishing to avoid RRSO, within a prospective clinical trial.
    Familial Cancer 07/2015; DOI:10.1007/s10689-015-9823-y · 1.98 Impact Factor

Publication Stats

7k Citations
1,671.47 Total Impact Points


  • 2012-2015
    • The Ohio State University
      • College of Nursing
      Columbus, Ohio, United States
  • 2005-2015
    • University College London
      • Institute for Women's Health
      Londinium, England, United Kingdom
    • Oregon Health and Science University
      • School of Nursing
      Portland, OR, United States
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2014
    • Columbus State University
      Columbus, Georgia, United States
  • 2007-2014
    • Arizona State University
      • College of Nursing and Health Innovation
      Phoenix, Arizona, United States
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • University of Nottingham
      • Centre of Evidence Based Dermatology
      Nottigham, England, United Kingdom
  • 2007-2012
    • King's College London
      • Department of Psychology
      Londinium, England, United Kingdom
  • 2010
    • Queensland Institute of Medical Research
      Brisbane, Queensland, Australia
  • 2009
    • British Gynaecological Cancer Society
      Londinium, England, United Kingdom
    • University of Bristol
      Bristol, England, United Kingdom
  • 2005-2009
    • University of Illinois at Chicago
      • • Department of Biobehavioral Health Science
      • • College of Nursing
      Chicago, Illinois, United States
  • 1999-2006
    • Queen Mary, University of London
      • Oral Pathology
      Londinium, England, United Kingdom
  • 2003
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2002-2003
    • University of Utah
      • College of Nursing
      Salt Lake City, Utah, United States
    • Salt Lake City Community College
      Salt Lake City, Utah, United States
  • 2000-2002
    • Indiana University-Purdue University Indianapolis
      • School of Nursing
      Indianapolis, IN, United States
    • Royal Cornwall Hospitals NHS Trust
      Truro, England, United Kingdom