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  1. Article ; Online: A DNA methylation signature in the stress driver gene Fkbp5 indicates a neuropathic component in chronic pain.

    Maiarù, Maria / Acton, Richard J / Woźniak, Eva L / Mein, Charles A / Bell, Christopher G / Géranton, Sandrine M

    Clinical epigenetics

    2023  Volume 15, Issue 1, Page(s) 155

    Abstract: Background: Epigenetic changes can bring insight into gene regulatory mechanisms associated with disease pathogenicity, including chronicity and increased vulnerability. To date, we are yet to identify genes sensitive to epigenetic regulation that ... ...

    Abstract Background: Epigenetic changes can bring insight into gene regulatory mechanisms associated with disease pathogenicity, including chronicity and increased vulnerability. To date, we are yet to identify genes sensitive to epigenetic regulation that contribute to the maintenance of chronic pain and with an epigenetic landscape indicative of the susceptibility to persistent pain. Such genes would provide a novel opportunity for better pain management, as their epigenetic profile could be targeted for the treatment of chronic pain or used as an indication of vulnerability for prevention strategies. Here, we investigated the epigenetic profile of the gene Fkbp5 for this potential, using targeted bisulphite sequencing in rodent pre-clinical models of chronic and latent hypersensitive states.
    Results: The Fkbp5 promoter DNA methylation (DNAm) signature in the CNS was significantly different between models of persistent pain, and there was a significant correlation between CNS and peripheral blood Fkbp5 DNAm, indicating that further exploration of Fkbp5 promoter DNAm as an indicator of chronic pain pathogenic origin is warranted. We also found that maternal separation, which promotes the persistency of inflammatory pain in adulthood, was accompanied by long-lasting reduction in Fkbp5 DNAm, suggesting that Fkbp5 DNAm profile may indicate the increased vulnerability to chronic pain in individuals exposed to trauma in early life.
    Conclusions: Overall, our data demonstrate that the Fkbp5 promoter DNAm landscape brings novel insight into the differing pathogenic origins of chronic pain, may be able to stratify patients and predict the susceptibility to chronic pain.
    MeSH term(s) Humans ; Chronic Pain/genetics ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression Regulation ; Maternal Deprivation ; Tacrolimus Binding Proteins/genetics
    Chemical Substances tacrolimus binding protein 5 (EC 5.2.1.8) ; Tacrolimus Binding Proteins (EC 5.2.1.-)
    Language English
    Publishing date 2023-09-30
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553921-8
    ISSN 1868-7083 ; 1868-7075
    ISSN (online) 1868-7083
    ISSN 1868-7075
    DOI 10.1186/s13148-023-01569-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Deep palmar phenotyping in atopic eczema: patterns associated with filaggrin variants, disease severity and barrier function in a South Asian population.

    Thomas, Bjorn R / Tan, Xiang Li / Van Duijvenboden, Stefan / Hogan, Sarah C / Hughes, Aaron J / Tawfik, Soha S / Dhoat, Sasha / Atkar, Ravinder / Robinson, Elizabeth J / Rahman, Syedia R / Rahman, Samiha / Ahmed, Rehana A / Begum, Rubina / Khanam, Habiba / Bourne, Emma L / Wozniak, Eva L / Mein, Charles A / Kelsell, David P / O'Toole, Edel A

    The British journal of dermatology

    2023  Volume 188, Issue 6, Page(s) 785–792

    Abstract: Background: Hyperlinear palms are described as a feature of loss-of-function (LoF) variants in filaggrin (FLG).: Objectives: To explore the phenotype of participants (age < 31 years) with atopic eczema of Bangladeshi ancestry from East London and ... ...

    Abstract Background: Hyperlinear palms are described as a feature of loss-of-function (LoF) variants in filaggrin (FLG).
    Objectives: To explore the phenotype of participants (age < 31 years) with atopic eczema of Bangladeshi ancestry from East London and investigate which factors best associate with LoF FLG variants.
    Methods: A cross-sectional study with participants recruited between May 2018 and December 2020. Patterns of palmar linearity were categorized and modelled with the Eczema Area and Severity Index (EASI), transepidermal water loss (TEWL), skin hydration (SH) and LoF FLG variants.
    Results: There were 506 complete cases available. Five palm patterns were noted. The 'prominent diamond' pattern associated best with EASI [marginal effects (ME) 2.53, 95% confidence interval (CI) 1.74-3.67], SH (ME 0.85, 95% CI 0.78-0.96) and TEWL (ME 1.32, 95% CI 1.11-1.62). Using five palm patterns had some ability to discriminate LoF FLG variants [area under the receiver operator characteristic (AUROC) 76.32%, 95% CI 71.91-80.73], improving to 77.99% (73.70-82.28) with the addition of SH. In subgroup analysis with only fine perpendicular/prominent diamond patterns the AUROC was 89.11% (95% CI 84.02-94.19).
    Conclusions: This was a single-centre study design with humans classifying clinical patterns. The stability of temperature and humidity was not guaranteed across TEWL and SH measurements despite using a climate-controlled room. Palm patterns associate with EASI and TEWL. The fine perpendicular/prominent diamond patterns are markers to detect the absence/presence of LoF FLG variants, respectively.
    MeSH term(s) Humans ; Adult ; Dermatitis, Atopic/genetics ; Filaggrin Proteins ; Cross-Sectional Studies ; Eczema/genetics ; Patient Acuity ; Intermediate Filament Proteins/genetics ; Intermediate Filament Proteins/metabolism ; Mutation/genetics ; Genetic Predisposition to Disease/genetics
    Chemical Substances Filaggrin Proteins ; Intermediate Filament Proteins
    Language English
    Publishing date 2023-03-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1093/bjd/ljad036
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  3. Article ; Online: Genotype-independent association between vitamin D deficiency and polycystic ovarian syndrome in Lahore, Pakistan.

    Lone, Nasira M / Riaz, Saba / Eusaph, Amna Z / Mein, Charles A / Wozniak, Eva L / Xenakis, Theodoros / Wu, Zhenqiang / Younis, Sidra / Jolliffe, David A / Junaid, Kashaf / Martineau, Adrian R

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 2290

    Abstract: Both vitamin D deficiency and single nucleotide polymorphisms (SNPs) in the gene encoding the vitamin D receptor (VDR) have been widely reported to associate with susceptibility to polycystic ovarian syndrome (PCOS). A case-control study was conducted to ...

    Abstract Both vitamin D deficiency and single nucleotide polymorphisms (SNPs) in the gene encoding the vitamin D receptor (VDR) have been widely reported to associate with susceptibility to polycystic ovarian syndrome (PCOS). A case-control study was conducted to study the influence of vitamin D status and genotpye for 24 SNPs in four genes in the vitamin D pathway (VDR, DBP, CYP27B1, CYP24A1) on PCOS. Statistical analyses were conducted to identify phenotypic and genotypic factors associated with risk of PCOS and to test for interactions between genotype and vitamin D status. PCOS was independently associated with lower age, higher body mass index, lower waist-hip ratio, vitamin D deficiency (serum 25-hydroxyvitamin D concentration <10 ng/mL), lack of outdoor exercise, increased fasting glucose and a family history of PCOS in at least one first degree relative. No statistically significant association was observed between the genotype of any SNP investigated and risk of PCOS, either as a main effect or in interaction with vitamin D status. We report a strong and independent association between vitamin D deficiency and risk of PCOS in Pakistan, that was not modified by genetic variation in the vitamin D pathway.
    MeSH term(s) 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Adult ; Age Factors ; Body Mass Index ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Pakistan/epidemiology ; Polycystic Ovary Syndrome/blood ; Polycystic Ovary Syndrome/epidemiology ; Polycystic Ovary Syndrome/etiology ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol/genetics ; Risk Assessment ; Risk Factors ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D Deficiency/blood ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/epidemiology ; Vitamin D Deficiency/genetics ; Vitamin D-Binding Protein/genetics ; Vitamin D3 24-Hydroxylase/genetics ; Young Adult
    Chemical Substances GC protein, human ; Receptors, Calcitriol ; VDR protein, human ; Vitamin D-Binding Protein ; Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H) ; CYP24A1 protein, human (EC 1.14.15.16) ; Vitamin D3 24-Hydroxylase (EC 1.14.15.16) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18) ; CYP27B1 protein, human (EC 1.14.15.18)
    Language English
    Publishing date 2020-02-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-59228-4
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  4. Article ; Online: Recruitment of newly diagnosed ovarian cancer patients proved challenging in a multicentre biobanking study.

    Balogun, Nyaladzi / Gentry-Maharaj, Aleksandra / Wozniak, Eva L / Lim, Anita / Ryan, Andy / Ramus, Susan J / Ford, Jeremy / Burnell, Matthew / Widschwendter, Martin / Gessler, Sue F / Gayther, Simon A / Jacobs, Ian J / Menon, Usha

    Journal of clinical epidemiology

    2010  Volume 64, Issue 5, Page(s) 525–530

    Abstract: Objective: To explore the challenges of recruiting ovarian cancer patients and healthy controls to a cancer biobanking study.: Study design and setting: The study was set up in gynecological cancer centers in 10 National Health Service trusts across ... ...

    Abstract Objective: To explore the challenges of recruiting ovarian cancer patients and healthy controls to a cancer biobanking study.
    Study design and setting: The study was set up in gynecological cancer centers in 10 National Health Service trusts across the United Kingdom. Women were approached if they were undergoing investigations/awaiting treatment for ovarian cancer, had a previous diagnosis of ovarian cancer, or were attending for annual screening in an ovarian cancer screening trial. Those who consented completed a detailed epidemiologic questionnaire, provided blood and tissue samples if appropriate.
    Results: The overall proportion of those recruited compared with the expected targets was 76.4% for healthy controls, 86.0% for old cases, and 46.9% for new cases. Only 4 of 10 (40%) centers recruited over 50% of their target for new cases. Unwillingness to participate was reported as primarily because of patients being too unwell, wanting to focus only on their treatment, or having insufficient time because of conflicting medical appointments. Concerns about use of personal data or tissue and blood samples for genetic research and lack of direct benefit were reported as significant challenges to recruitment.
    Conclusion: When setting recruitment targets for patients undergoing investigations or awaiting treatment for cancer (new cases), it is important to consider lower response rates because of various patient, logistical, and trial-specific challenges.
    MeSH term(s) Aged ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/psychology ; Patient Compliance/statistics & numerical data ; Patient Selection ; Quality of Life/psychology ; Registries ; Surveys and Questionnaires ; Tissue Banks/statistics & numerical data ; United Kingdom
    Language English
    Publishing date 2010-11-13
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 639306-8
    ISSN 1878-5921 ; 0895-4356
    ISSN (online) 1878-5921
    ISSN 0895-4356
    DOI 10.1016/j.jclinepi.2010.07.008
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  5. Article ; Online: Biomarker-based ovarian carcinoma typing: a histologic investigation in the ovarian tumor tissue analysis consortium.

    Köbel, Martin / Kalloger, Steve E / Lee, Sandra / Duggan, Máire A / Kelemen, Linda E / Prentice, Leah / Kalli, Kimberly R / Fridley, Brooke L / Visscher, Daniel W / Keeney, Gary L / Vierkant, Robert A / Cunningham, Julie M / Chow, Christine / Ness, Roberta B / Moysich, Kirsten / Edwards, Robert / Modugno, Francesmary / Bunker, Clareann / Wozniak, Eva L /
    Benjamin, Elizabeth / Gayther, Simon A / Gentry-Maharaj, Aleksandra / Menon, Usha / Gilks, C Blake / Huntsman, David G / Ramus, Susan J / Goode, Ellen L

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

    2013  Volume 22, Issue 10, Page(s) 1677–1686

    Abstract: Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue ... ...

    Abstract Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model.
    Methods: Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review.
    Results: The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37-0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2.
    Conclusions: Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type.
    Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Ovarian Epithelial ; Cohort Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Glandular and Epithelial/chemistry ; Neoplasms, Glandular and Epithelial/classification ; Neoplasms, Glandular and Epithelial/pathology ; Ovarian Neoplasms/chemistry ; Ovarian Neoplasms/classification ; Ovarian Neoplasms/pathology ; Tissue Array Analysis ; Treatment Outcome
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2013-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1153420-5
    ISSN 1538-7755 ; 1055-9965
    ISSN (online) 1538-7755
    ISSN 1055-9965
    DOI 10.1158/1055-9965.EPI-13-0391
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  6. Article ; Online: Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.

    Sieh, Weiva / Köbel, Martin / Longacre, Teri A / Bowtell, David D / deFazio, Anna / Goodman, Marc T / Høgdall, Estrid / Deen, Suha / Wentzensen, Nicolas / Moysich, Kirsten B / Brenton, James D / Clarke, Blaise A / Menon, Usha / Gilks, C Blake / Kim, Andre / Madore, Jason / Fereday, Sian / George, Joshy / Galletta, Laura /
    Lurie, Galina / Wilkens, Lynne R / Carney, Michael E / Thompson, Pamela J / Matsuno, Rayna K / Kjær, Susanne Krüger / Jensen, Allan / Høgdall, Claus / Kalli, Kimberly R / Fridley, Brooke L / Keeney, Gary L / Vierkant, Robert A / Cunningham, Julie M / Brinton, Louise A / Yang, Hannah P / Sherman, Mark E / García-Closas, Montserrat / Lissowska, Jolanta / Odunsi, Kunle / Morrison, Carl / Lele, Shashikant / Bshara, Wiam / Sucheston, Lara / Jimenez-Linan, Mercedes / Driver, Kristy / Alsop, Jennifer / Mack, Marie / McGuire, Valerie / Rothstein, Joseph H / Rosen, Barry P / Bernardini, Marcus Q / Mackay, Helen / Oza, Amit / Wozniak, Eva L / Benjamin, Elizabeth / Gentry-Maharaj, Aleksandra / Gayther, Simon A / Tinker, Anna V / Prentice, Leah M / Chow, Christine / Anglesio, Michael S / Johnatty, Sharon E / Chenevix-Trench, Georgia / Whittemore, Alice S / Pharoah, Paul D P / Goode, Ellen L / Huntsman, David G / Ramus, Susan J

    The Lancet. Oncology

    2013  Volume 14, Issue 9, Page(s) 853–862

    Abstract: Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone ... ...

    Abstract Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival.
    Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed.
    Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74).
    Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer.
    Funding: Carraresi Foundation and others.
    MeSH term(s) Adenocarcinoma, Clear Cell/metabolism ; Adenocarcinoma, Clear Cell/mortality ; Adenocarcinoma, Clear Cell/pathology ; Adenocarcinoma, Mucinous/metabolism ; Adenocarcinoma, Mucinous/mortality ; Adenocarcinoma, Mucinous/pathology ; Biomarkers, Tumor/metabolism ; Carcinoma, Endometrioid/metabolism ; Carcinoma, Endometrioid/mortality ; Carcinoma, Endometrioid/pathology ; Case-Control Studies ; Cystadenocarcinoma, Serous/metabolism ; Cystadenocarcinoma, Serous/mortality ; Cystadenocarcinoma, Serous/pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Ovary/metabolism ; Ovary/pathology ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; Tissue Array Analysis
    Chemical Substances Biomarkers, Tumor ; Receptors, Estrogen ; Receptors, Progesterone
    Language English
    Publishing date 2013-07-09
    Publishing country England
    Document type Comparative Study ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(13)70253-5
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  7. Article ; Online: Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.

    Shen, Hui / Fridley, Brooke L / Song, Honglin / Lawrenson, Kate / Cunningham, Julie M / Ramus, Susan J / Cicek, Mine S / Tyrer, Jonathan / Stram, Douglas / Larson, Melissa C / Köbel, Martin / Ziogas, Argyrios / Zheng, Wei / Yang, Hannah P / Wu, Anna H / Wozniak, Eva L / Woo, Yin Ling / Winterhoff, Boris / Wik, Elisabeth /
    Whittemore, Alice S / Wentzensen, Nicolas / Weber, Rachel Palmieri / Vitonis, Allison F / Vincent, Daniel / Vierkant, Robert A / Vergote, Ignace / Van Den Berg, David / Van Altena, Anne M / Tworoger, Shelley S / Thompson, Pamela J / Tessier, Daniel C / Terry, Kathryn L / Teo, Soo-Hwang / Templeman, Claire / Stram, Daniel O / Southey, Melissa C / Sieh, Weiva / Siddiqui, Nadeem / Shvetsov, Yurii B / Shu, Xiao-Ou / Shridhar, Viji / Wang-Gohrke, Shan / Severi, Gianluca / Schwaab, Ira / Salvesen, Helga B / Rzepecka, Iwona K / Runnebaum, Ingo B / Rossing, Mary Anne / Rodriguez-Rodriguez, Lorna / Risch, Harvey A / Renner, Stefan P / Poole, Elizabeth M / Pike, Malcolm C / Phelan, Catherine M / Pelttari, Liisa M / Pejovic, Tanja / Paul, James / Orlow, Irene / Omar, Siti Zawiah / Olson, Sara H / Odunsi, Kunle / Nickels, Stefan / Nevanlinna, Heli / Ness, Roberta B / Narod, Steven A / Nakanishi, Toru / Moysich, Kirsten B / Monteiro, Alvaro N A / Moes-Sosnowska, Joanna / Modugno, Francesmary / Menon, Usha / McLaughlin, John R / McGuire, Valerie / Matsuo, Keitaro / Adenan, Noor Azmi Mat / Massuger, Leon F A G / Lurie, Galina / Lundvall, Lene / Lubiński, Jan / Lissowska, Jolanta / Levine, Douglas A / Leminen, Arto / Lee, Alice W / Le, Nhu D / Lambrechts, Sandrina / Lambrechts, Diether / Kupryjanczyk, Jolanta / Krakstad, Camilla / Konecny, Gottfried E / Kjaer, Susanne Krüger / Kiemeney, Lambertus A / Kelemen, Linda E / Keeney, Gary L / Karlan, Beth Y / Karevan, Rod / Kalli, Kimberly R / Kajiyama, Hiroaki / Ji, Bu-Tian / Jensen, Allan / Jakubowska, Anna / Iversen, Edwin / Hosono, Satoyo / Høgdall, Claus K / Høgdall, Estrid / Hoatlin, Maureen / Hillemanns, Peter / Heitz, Florian / Hein, Rebecca / Harter, Philipp / Halle, Mari K / Hall, Per / Gronwald, Jacek / Gore, Martin / Goodman, Marc T / Giles, Graham G / Gentry-Maharaj, Aleksandra / Garcia-Closas, Montserrat / Flanagan, James M / Fasching, Peter A / Ekici, Arif B / Edwards, Robert / Eccles, Diana / Easton, Douglas F / Dürst, Matthias / du Bois, Andreas / Dörk, Thilo / Doherty, Jennifer A / Despierre, Evelyn / Dansonka-Mieszkowska, Agnieszka / Cybulski, Cezary / Cramer, Daniel W / Cook, Linda S / Chen, Xiaoqing / Charbonneau, Bridget / Chang-Claude, Jenny / Campbell, Ian / Butzow, Ralf / Bunker, Clareann H / Brueggmann, Doerthe / Brown, Robert / Brooks-Wilson, Angela / Brinton, Louise A / Bogdanova, Natalia / Block, Matthew S / Benjamin, Elizabeth / Beesley, Jonathan / Beckmann, Matthias W / Bandera, Elisa V / Baglietto, Laura / Bacot, François / Armasu, Sebastian M / Antonenkova, Natalia / Anton-Culver, Hoda / Aben, Katja K / Liang, Dong / Wu, Xifeng / Lu, Karen / Hildebrandt, Michelle A T / Schildkraut, Joellen M / Sellers, Thomas A / Huntsman, David / Berchuck, Andrew / Chenevix-Trench, Georgia / Gayther, Simon A / Pharoah, Paul D P / Laird, Peter W / Goode, Ellen L / Pearce, Celeste Leigh

    Nature communications

    2012  Volume 4, Page(s) 1628

    Abstract: HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk ... ...

    Abstract HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
    MeSH term(s) DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Genetic Predisposition to Disease ; Hepatocyte Nuclear Factor 1-beta/genetics ; Humans ; Ovarian Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic
    Chemical Substances HNF1B protein, human ; Hepatocyte Nuclear Factor 1-beta (138674-15-4)
    Keywords covid19
    Language English
    Publishing date 2012-07-18
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms2629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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