Elizabeth M Poole

Brigham and Women's Hospital, Boston, Massachusetts, United States

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Publications (103)671.05 Total impact

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    ABSTRACT: Lifestyle factors have been well-studied in relation to breast cancer prognosis overall, however, associations of lifestyle and late outcomes (>5 after diagnosis) have been much less studied, and no studies have focused on ER+ breast cancer survivors, who may have high risk of late recurrence and mortality. We utilized a large prospective pooling study to evaluate the associations of lifestyle factors with late recurrence and all-cause mortality among 6,295 5-year ER+ stage I-III breast cancer survivors. Pooled and harmonized data were available on clinical factors and lifestyle factors (pre-to-post-diagnosis weight change, BMI (kg/m(2) ), recreational physical activity (PA), alcohol intake, and smoking history), measured on average 2.1 years after diagnosis. Updated information for weight only was available. Study heterogeneity was evaluated by the Q statistic. Multivariable Cox regression models were stratified by study. Adjusting for clinical factors and potential confounders, ≥10% weight gain and obesity (BMI 30-34.99 and ≥35) were associated with increased risk of late recurrence (HRs (95% CIs): 1.24 (1.00-1.53), 1.40 (1.05-1.86) and 1.41 (1.02-1.93), respectively). Daily alcohol intake was associated with late recurrence, 1.28 (1.01-1.62). PA was inversely associated with late all-cause mortality (0.81 (0.71-0.93) and 0.71 (0.61-0.82) for 4.9-<17.4 and ≥17.4 MET-h/wk). A U-shaped association was observed for late all-cause mortality and BMI using updated weight (1.42 (1.15-1.74) and 1.40 (1.09-1.81), <21.5 and ≥ 35, respectively). Smoking was associated with increased risk of late outcomes. In this large prospective pooling project, modifiable lifestyle factors were associated with late outcomes among long-term ER+ breast cancer survivors. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 11/2015; DOI:10.1002/ijc.29940 · 5.09 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: Objectives: While emerging evidence supports a possible link between depression and ovarian cancer progression, no prospective studies have explored the association with ovarian cancer risk. Methods: We prospectively followed 77 451 women from the Nurses' Health Study (1992-2010) and 106 452 women from the Nurses' Health Study II (1993-2011). Depression was defined as having one or more of the following: a 5-item Mental Health Index (MHI-5) score≤52, antidepressant use, or physician-diagnosed depression. Multivariate-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between depression and incident ovarian cancer. Results: We documented 698 incident cases of epithelial ovarian cancer during follow-up. In multivariable analyses, depression assessed 2-4years before cancer diagnosis was associated with a modestly higher incidence of ovarian cancer (HR=1.30, 95% CI1.05-1.60). Compared to women with persistent negative depression status, the adjusted HRs were 1.34 (95% CI 1.01-1.76) for women with persistent positive depression status and 1.28 (95% CI 0.88-1.85) for women with worsening depression status over follow-up. The association did not appear to vary by ovarian cancer risk factors or tumor characteristics. Conclusions: Our findings suggest that depression may be associated with a modestly increased risk of ovarian cancer. Given the relatively high prevalence of depression in women, future work in larger prospective human studies is needed to confirm our results.
    Gynecologic Oncology 10/2015; DOI:10.1016/j.ygyno.2015.10.004 · 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: Despite multiple hypotheses for a protective effect, epidemiologic findings are inconsistent regarding the association between physical activity and risk of ovarian cancer. Considering physical activity assessment at different times of life, including pre- and postmenopause, may be important for explaining these discrepancies. Therefore, we examined the risk of ovarian cancer according to total, premenopausal and postmenopausal physical activity among 85,462 women from the Nurses' Health Study and 112,679 women from the Nurses' Health Study II. Leisure-time physical activity was prospectively assessed about every 2-4 years using validated questionnaires, and characterized as metabolic equivalent task hours per week (MET-hrs/week), which combines exercise duration and intensity. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for these associations. We identified 815 incident epithelial ovarian cancer cases during 24 years of follow-up. A modestly increased ovarian cancer risk was observed for high levels of total cumulative average physical activity and a suggestively increased risk for low activity. Compared with 3-9 MET-hrs/week, HRs (95% CIs) were 1.26 (1.02, 1.55) for ≥27 MET-hrs/week (equivalent to 1 hr/day of brisk walking) and 1.19 (0.94, 1.52) for <3 MET-hrs/week. This association was limited to premenopausal physical activity (comparable HR [95% CI] of 1.50 [1.13, 1.97] and 1.29 [0.95, 1.75], respectively). Postmenopausal physical activity was not associated with risk. Our data do not support a protective role of physical activity for ovarian cancer. The increased risk associated with physical activity during premenopausal years and the underlying etiology require further investigation. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 09/2015; DOI:10.1002/ijc.29834 · 5.09 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):AS10-AS10. DOI:10.1158/1557-3265.OVCASYMP14-AS10 · 8.72 Impact Factor
  • Elizabeth M. Poole · Laura Kubzansky · Olivia I. Okereke · Shelley S. Tworoger ·

    Clinical Cancer Research 08/2015; 21(16 Supplement):POSTER-CTRL-1212-POSTER-CTRL-1212. DOI:10.1158/1557-3265.OVCASYMP14-POSTER-CTRL-1212 · 8.72 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):854-854. DOI:10.1158/1538-7445.AM2015-854 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):858-858. DOI:10.1158/1538-7445.AM2015-858 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):LB-180-LB-180. DOI:10.1158/1538-7445.AM2015-LB-180 · 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: journals.permissions@oup.com.
    Human Molecular Genetics 07/2015; 24(20). DOI:10.1093/hmg/ddv306 · 6.39 Impact Factor
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    ABSTRACT: Melatonin has anti-carcinogenic properties, including modulation of estradiol production, cell cycle regulation, and promotion of apoptosis. Urinary melatonin has been inversely associated with breast cancer in some studies, but the association with ovarian cancer has not been investigated. We measured urinary 6-sulfatoxymelatonin (aMT6s) in nested ovarian cancer case-control studies in the Nurses' Health Study (NHS; n = 100 cases; 199 controls) and NHSII (n = 52 cases; 105 controls); samples were mainly from first morning voids. Controls were matched to cases on year of birth, menopause status, use of menopausal hormone therapy, and urine collection characteristics. We evaluated the association of tertiles of aMT6s, corrected for creatinine concentrations, with risk of ovarian cancer using conditional logistic regression. Models were adjusted for key ovarian cancer risk factors, and we additionally evaluated adjustment for usual sleep duration, snoring, and history of rotating night shift work. aMT6s was not significantly associated with risk of ovarian cancer. In multivariable models, the odds ratio comparing the highest tertile of aMT6s to the lowest was 0.79, 95 % confidence interval (CI) 0.40-1.56 in the NHS and 2.88, and 95 % CI in the NHSII 0.97-8.52. Additional adjustment for sleep habits and night shift work had little impact on the observed results. We observed no clear association between urinary melatonin and ovarian cancer risk. These results are consistent with our previous study in which we reported no association between night shift work and ovarian cancer; however, given the small sample size in our study, additional evaluation in larger studies is warranted.
    Cancer Causes and Control 07/2015; 26(10). DOI:10.1007/s10552-015-0640-2 · 2.74 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: Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions with respect to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations. Two hundred eighty-eight candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 incident CRC case-control matched pairs in the Women's Health Initiative Observational Study cohort. FOCM biomarkers (red blood cell [RBC] folate, plasma folate, pyridoxal-5'-phosphate [PLP], vitamin B12, and homocysteine) and self-reported alcohol consumption were measured at the baseline. Conditional logistic regression was implemented; effect modification was examined on the basis of known enzyme-nutrient relations. Statistically significant associations were observed between CRC risk and functionally defined candidate SNPs of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1; K134R), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; P450R), and PR domain containing 2 with ZNF domain (PRDM2; S450N) and a literature candidate SNP of thymidylate synthase (TYMS; g.676789A>T; nominal P < .05). In addition, suggestive associations were noted for tagging SNPs in cystathionine-β-synthase (CBS), dihydrofolate reductase (DHFR), DNA (cytosine-5-)-methyltransferase 3β (DNMT3B), methionine adenosyltransferase I α (MAT1A), MTHFD1, and MTRR (nominal P < .05; adjusted P, not significant). Significant interactions between nutrient biomarkers and candidate polymorphisms were observed for 1) plasma/RBC folate and folate hydrolase 1 (FOLH1), paraoxonase 1 (PON1), transcobalamin II (TCN2), DNMT1, and DNMT3B; 2) plasma PLP and TYMS TS3; 3) plasma B12 and betaine-homocysteine S-methyltransferase 2 (BHMT2); and 4) homocysteine and methylenetetrahydrofolate reductase (MTHFR) and alanyl-transfer RNA synthetase (AARS). Genetic variants in FOCM genes are associated with CRC risk among postmenopausal women. FOCM nutrients continue to emerge as effect modifiers of genetic influences on CRC risk. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    Cancer 06/2015; 121(20). DOI:10.1002/cncr.29465 · 4.89 Impact Factor
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    ABSTRACT: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
    PLoS ONE 06/2015; 10(6):e0128106. DOI:10.1371/journal.pone.0128106 · 3.23 Impact Factor
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    ABSTRACT: Disease classification system increasingly incorporates information on pathogenic mechanisms to predict clinical outcomes and response to therapy and intervention. Technological advancements to interrogate omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, interactomics, etc.) provide widely open opportunities in population-based research. Molecular pathological epidemiology (MPE) represents integrative science of molecular pathology and epidemiology. This unified paradigm requires multidisciplinary collaboration between pathology, epidemiology, biostatistics, bioinformatics, and computational biology. Integration of these fields enables better understanding of etiologic heterogeneity, disease continuum, causal inference, and the impact of environment, diet, lifestyle, host factors (including genetics and immunity), and their interactions on disease evolution. Hence, the Second International MPE Meeting was held in Boston in December 2014, with aims to: (1) develop conceptual and practical frameworks; (2) cultivate and expand opportunities; (3) address challenges; and (4) initiate the effort of specifying guidelines for MPE. The meeting mainly consisted of presentations of method developments and recent data in various malignant neoplasms and tumors (breast, prostate, ovarian and colorectal cancers, renal cell carcinoma, lymphoma, and leukemia), followed by open discussion sessions on challenges and future plans. In particular, we recognized need for efforts to further develop statistical methodologies. This meeting provided an unprecedented opportunity for interdisciplinary collaboration, consistent with the purposes of the Big Data to Knowledge, Genetic Associations and Mechanisms in Oncology, and Precision Medicine Initiative of the US National Institute of Health. The MPE meeting series can help advance transdisciplinary population science and optimize training and education systems for twenty-first century medicine and public health.
    Cancer Causes and Control 05/2015; 26(7). DOI:10.1007/s10552-015-0596-2 · 2.74 Impact Factor
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    ABSTRACT: Objective: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods: Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results: We found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations. Conclusions: rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
    Gynecologic Oncology 05/2015; DOI:10.1016/j.ygyno.2015.04.034 · 3.77 Impact Factor

Publication Stats

904 Citations
671.05 Total Impact Points


  • 2013-2015
    • Brigham and Women's Hospital
      • • Channing Division of Network Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2011-2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2011-2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2005-2014
    • Fred Hutchinson Cancer Research Center
      • • Division of Public Health Sciences
      • • Cancer Prevention Program
      Seattle, Washington, United States
  • 2010
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 2006-2010
    • University of Washington Seattle
      • Department of Epidemiology
      Seattle, Washington, United States