Displaying publications 1 - 20 of 27 in total

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  1. Fortner RT, Ose J, Merritt MA, Schock H, Tjønneland A, Hansen L, et al.
    Int. J. Cancer, 2015 Sep 01;137(5):1196-208.
    PMID: 25656413 DOI: 10.1002/ijc.29471
    Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet  = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet  = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/epidemiology; Neoplasms, Glandular and Epithelial/pathology*; Neoplasms, Glandular and Epithelial/prevention & control*
  2. Rusinahayati, M., Sivanesaratnam, V., Jayalashmi, Noraihan, M. N.
    MyJurnal
    Objective: The purpose of this study was to evaluate the clinical behaviour, pathological findings, survival and prognostic factors in young women in comparison to menopausal women with epithelial ovarian malignancy. Methods: A retrospective analysis of 141 patients (67 for age below 40 years and 74 menopausal) treated between 1980 and 2000 was conducted. Results: Irrespective of the stage, the most common clinical presentation was abdominal distension in both young (78%) and menopausal women (66%). In young women, 52% presented at an early stage of the disease and in menopausal women this was seen in 22% (p-value
    Matched MeSH terms: Neoplasms, Glandular and Epithelial
  3. Hussaini HM, Angel CM, Speight PM, Firth NA, Rich AM
    Head Neck Pathol, 2012 Dec;6(4):471-5.
    PMID: 22427262 DOI: 10.1007/s12105-012-0350-y
    The hallmark of the histology of epithelial-myoepithelial carcinoma (EMC) is the presence of a regular repetitive mixture of bilayered duct-like structures with an outer layer of myoepithelial cells and inner ductal epithelial cells. Clear cell change in the myoepithelial component is common, but clearing of both cell types, giving an impression of a monocellular neoplasm, is rare. A parotid biopsy was received from an 83-year-old male and subject to routine histologic processing for conventional staining and immunohistochemistry. The encapsulated tumour was composed of sheets of PAS/diastase negative clear cells, separated by fibrous septae. The clear myoepithelial cells were positive for S-100 protein, SMA, and p63 and negative for CK19 and surrounded CK19-positive luminal cells. It is important to utilise immunohistochemistry to differentiate this tumour from others with a similar histologic pattern. Information about the behaviour of the double-clear EMC is limited since there are few cases reported.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/metabolism; Neoplasms, Glandular and Epithelial/pathology*
  4. Amankwah EK, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Chornokur G, et al.
    Genet. Epidemiol., 2015 Dec;39(8):689-97.
    PMID: 26399219 DOI: 10.1002/gepi.21921
    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.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/epidemiology*
  5. Ab Mutalib NS, Syafruddin SE, Md Zain RR, Mohd Dali AZ, Mohd Yunos RI, Saidin S, et al.
    BMC Res Notes, 2014;7:805.
    PMID: 25404506 DOI: 10.1186/1756-0500-7-805
    High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/epidemiology
  6. Permuth JB, Pirie A, Ann Chen Y, Lin HY, Reid BM, Chen Z, et al.
    Hum. Mol. Genet., 2016 08 15;25(16):3600-3612.
    PMID: 27378695 DOI: 10.1093/hmg/ddw196
    Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P  P≥5.0 ×10 -  7) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 × 10 -  5; PSKAT-o = 9.23 × 10 -  4) and KRT13 (PAML = 1.67 × 10 -  4; PSKAT-o = 1.07 × 10 -  5), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/pathology
  7. Chornokur G, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Amankwah EK, et al.
    PLoS ONE, 2015;10(6):e0128106.
    PMID: 26091520 DOI: 10.1371/journal.pone.0128106
    BACKGROUND: 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.

    METHODS: 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.

    RESULTS: 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).

    CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/epidemiology*; Neoplasms, Glandular and Epithelial/pathology
  8. Mohd Kamil MK, Ngiu CS, Md Isa N, Yaacob Y Y, Deborah Chew CH, Wong ZQ, et al.
    Med. J. Malaysia, 2018 02;73(1):60-62.
    PMID: 29531208 MyJurnal
    Neuroendocrine neoplasm is an epithelial neoplasm with predominant neuroendocrine differentiation that can arise from many organs in the body. We reported a rare case of gastric neuroendocrine carcinoma which accounts for less than 1% of all gastric tumours that is associated with poor prognosis. The recognition of this rare tumour in early stage is challenging and high suspicious into it might bring to early detection and so forth might improve the prognostication.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial
  9. Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, et al.
    Carcinogenesis, 2015 Nov;36(11):1341-53.
    PMID: 26424751 DOI: 10.1093/carcin/bgv138
    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 = 1.1×10(-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 = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*
  10. Obón-Santacana M, Peeters PH, Freisling H, Dossus L, Clavel-Chapelon F, Baglietto L, et al.
    Cancer Epidemiol. Biomarkers Prev., 2015 Jan;24(1):291-7.
    PMID: 25300475 DOI: 10.1158/1055-9965.EPI-14-0636
    Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 μg/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 μg/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10μg/d,1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/etiology*
  11. Young LS, Yap LF, Murray PG
    Nat. Rev. Cancer, 2016 12;16(12):789-802.
    PMID: 27687982 DOI: 10.1038/nrc.2016.92
    It is more than 50 years since the Epstein-Barr virus (EBV), the first human tumour virus, was discovered. EBV has subsequently been found to be associated with a diverse range of tumours of both lymphoid and epithelial origin. Progress in the molecular analysis of EBV has revealed fundamental mechanisms of more general relevance to the oncogenic process. This Timeline article highlights key milestones in the 50-year history of EBV and discusses how this virus provides a paradigm for exploiting insights at the molecular level in the diagnosis, treatment and prevention of cancer.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/virology
  12. Bešević J, Gunter MJ, Fortner RT, Tsilidis KK, Weiderpass E, Onland-Moret NC, et al.
    Br. J. Cancer, 2015 Dec 01;113(11):1622-31.
    PMID: 26554655 DOI: 10.1038/bjc.2015.377
    BACKGROUND: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521,330 total participants (approximately 370,000 women) aged 25-70 years at recruitment from 1992 to 2000.

    METHODS: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre.

    RESULTS: After a mean follow-up of 3.6 years (±3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR=0.80, 95% CI=0.62-1.03) and a significant survival benefit in long-term MHT users (⩾5 years use vs never use, HR=0.70, 95% CI=0.50-0.99, P(trend)=0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk.

    CONCLUSIONS: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.

    Matched MeSH terms: Neoplasms, Glandular and Epithelial/mortality*; Neoplasms, Glandular and Epithelial/pathology*
  13. Lawrenson K, Li Q, Kar S, Seo JH, Tyrer J, Spindler TJ, et al.
    Nat Commun, 2015 Sep 22;6:8234.
    PMID: 26391404 DOI: 10.1038/ncomms9234
    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.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/metabolism
  14. Maraei AA, Hatta AZ, Shiran MS, Tan GC
    Indian J Pathol Microbiol, 2012 Apr-Jun;55(2):187-91.
    PMID: 22771641 DOI: 10.4103/0377-4929.97865
    Ovarian cancer is the 6 th most common cancer among women. In ovarian tumors, the borderline category is not well defined due to the difficulty in assessing stromal invasion. The World Health Organization (WHO) defined it as tumor that lacks obvious invasion of the stroma with mitotic activity and nuclear abnormalities intermediate between clearly benign and unquestionably malignant. Telomerase is expressed in many human cancers and is hence a potential biomarker for cancer. Immunohistochemical study of anti-human telomerase enzyme reverse transcriptase (hTERT) antibody allows direct visualization of its expression. The aim of this study was to determine the expression of hTERT and serum CA-125 level in ovarian epithelial tumors, and their ability to distinguish borderline tumor from malignancy.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/classification; Neoplasms, Glandular and Epithelial/pathology*
  15. Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, et al.
    Nat. Genet., 2017 May;49(5):680-691.
    PMID: 28346442 DOI: 10.1038/ng.3826
    To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/pathology
  16. Siar CH, Ng KH
    Pathology, 2019 Aug;51(5):494-501.
    PMID: 31262562 DOI: 10.1016/j.pathol.2019.04.004
    The ameloblastoma is the most common and clinically significant odontogenic epithelial neoplasm known for its locally-invasive behaviour and high recurrence risk. Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells lose their epithelial characteristics and gain mesenchymal properties. EMT induction via transcription repression has been investigated in ameloblastoma. However, morphologically evident mesenchymal phenotypic transition remains ill-defined. To determine this, 24 unicystic (UA), 34 solid/multicystic (SA) and 18 recurrent ameloblastoma (RA) were immunohistochemically examined for three EMT-related mesenchymal markers, alpha smooth muscle actin (α-SMA), osteonectin and neuronal cadherin (N-cadherin). All three factors were heterogeneously detected in ameloblastoma samples (α-SMA, n=71/76, 93.4%; osteonectin, n=72/76, 94.7%; N-cadherin, n=24/76, 31.6%). In the tumoural parenchyma, immunoreactive cells were not morphologically distinct from their non-reactive cellular counterparts. Rather, α-SMA and osteonectin predominantly labelled the cytoplasm of central polyhedral > peripheral columnar/cuboidal tumour cells. N-cadherin demonstrated weak-to-moderate circumferential membranous staining in both neoplastic cell types and cytoplasmic expression in spindle-celled epithelium of desmoplastic amelobastoma. For all tumour subsets, α-SMA and osteonectin scored significantly higher in the stroma > parenchyma whilst α-SMA was overexpressed along the tumour invasive front > centre (p<0.05). Stromal N-cadherin scored higher in SA > UA and RA > UA (p<0.05). Other clinicopathological parameters showed no significant associations. Taken together, acquisition of mesenchymal traits without morphologically evident mesenchymal alteration suggests partial EMT in ameloblastoma. Stromal upregulation of these proteins in SA and RA implicates a role in local invasiveness.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial
  17. Linus-Lojikip S, Subramaniam V, Lim WY, Hss AS
    Complement Ther Clin Pract, 2019 Sep 06;37:73-85.
    PMID: 31521007 DOI: 10.1016/j.ctcp.2019.09.001
    BACKGROUND: This case series describes the survival outcomes of patients who underwent integrative medicine (IM) protocol for ovarian cancer, a treatment protocol, that integrated a carefully selected set of complementary and alternative medicine (CAM) into the conventional treatment for ovarian cancers.

    MATERIALS AND METHODS: Retrospective review of patients' medical records was conducted at a private medical centre that delivered the IM protocol for patients with advanced and recurrent ovarian cancers. We explored and analysed the overall survival and disease progressions of those who received the IM treatment for at least 2 months.

    RESULTS: Forty patients with advanced ovarian cancers fulfilled the inclusion criteria for this case series. An overall of 75% of the cases achieved remission with initial IM treatment, 17.5% had a partial response and 7.5% showed progressive disease. The overall 5-year survival for all 40 cases is 53.1%. When explored further, the 5-year survival for cases who received CAM only is 75%, and cases who received combined limited chemotherapy with CAM had a 5-year survival of 55%. At study endpoint, 11 cases died due to ovarian cancer.

    CONCLUSION: These findings suggest that CAM may be a valuable addition to conventional therapy to treat and improve the survival of patients with ovarian cancers. A formal randomized control trial is required to evaluate the efficacy and long-term outcomes of using IM to treat advanced and recurrent ovarian cancers.

    Matched MeSH terms: Neoplasms, Glandular and Epithelial
  18. Lu Y, Beeghly-Fadiel A, Wu L, Guo X, Li B, Schildkraut JM, et al.
    Cancer Res., 2018 09 15;78(18):5419-5430.
    PMID: 30054336 DOI: 10.1158/0008-5472.CAN-18-0951
    Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10-6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419-30. ©2018 AACR.
    Matched MeSH terms: Neoplasms, Glandular and Epithelial
  19. Merritt MA, Tzoulaki I, van den Brandt PA, Schouten LJ, Tsilidis KK, Weiderpass E, et al.
    Am. J. Clin. Nutr., 2016 Jan;103(1):161-7.
    PMID: 26607939 DOI: 10.3945/ajcn.115.118588
    BACKGROUND: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.

    OBJECTIVE: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.

    DESIGN: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.

    RESULTS: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).

    CONCLUSION: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.

    Matched MeSH terms: Neoplasms, Glandular and Epithelial/etiology*
  20. Hampras SS, Sucheston-Campbell LE, Cannioto R, Chang-Claude J, Modugno F, Dörk T, et al.
    Oncotarget, 2016 10 25;7(43):69097-69110.
    PMID: 27533245 DOI: 10.18632/oncotarget.10215
    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.

    METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.

    RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).

    CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

    Matched MeSH terms: Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/immunology
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