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  • 11
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    Study Comparing Human Papillomavirus (HPV) Real-Time Multiplex PCR and Hybrid Capture II INNO-LiPA v2 HPV Genotyping PCR Assays
    American Society for Microbiology ; 2009
    In:  Journal of Clinical Microbiology Vol. 47, No. 7 ( 2009-07), p. 2106-2113
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 47, No. 7 ( 2009-07), p. 2106-2113
    Abstract: Human papillomavirus (HPV) DNA genotyping is an essential test to establish efficacy in HPV vaccine clinical trials and HPV prevalence in natural history studies. A number of HPV DNA genotyping methods have been cited in the literature, but the comparability of the outcomes from the different methods has not been well characterized. Clinically, cytology is used to establish possible HPV infection. We evaluated the sensitivity and specificity of HPV multiplex PCR assays compared to those of the testing scheme of the Hybrid Capture II (HCII) assay followed by an HPV PCR/line hybridization assay (HCII-LiPA v2). SurePath residual samples were split into two aliquots. One aliquot was subjected to HCII testing followed by DNA extraction and LiPA v2 genotyping. The second aliquot was shipped to a second laboratory, where DNA was extracted and HPV multiplex PCR testing was performed. Comparisons were evaluated for 15 HPV types common in both assays. A slightly higher proportion of samples tested positive by the HPV multiplex PCR than by the HCII-LiPA v2 assay. The sensitivities of the multiplex PCR assay relative to those of the HCII-LiPA v2 assay for HPV types 6, 11, 16, and 18, for example, were 0.806, 0.646, 0.920, and 0.860, respectively; the specificities were 0.986, 0.998, 0.960, and 0.986, respectively. The overall comparability of detection of the 15 HPV types was quite high. Analyses of DNA genotype testing compared to cytology results demonstrated a significant discordance between cytology-negative (normal) and HPV DNA-positive results. This demonstrates the challenges of cytological diagnosis and the possibility that a significant number of HPV-infected cells may appear cytologically normal.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.01907-08
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2009
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  • 12
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    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus
    Springer Science and Business Media LLC ; 2016
    In:  Nature Communications Vol. 7, No. 1 ( 2016-09-07)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-09-07)
    Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC ( P =9.2 × 10 −20 ), ER-negative BC ( P =1.1 × 10 −13 ), BRCA1 -associated BC ( P =7.7 × 10 −16 ) and triple negative BC ( P -diff=2 × 10 −5 ). Genotype-gene expression associations are identified for candidate target genes ANKLE1 ( P =2 × 10 −3 ) and ABHD8 ( P 〈 2 × 10 −3 ). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8 , and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/ncomms12675
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
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  • 13
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    Association Study of Prostate Cancer Susceptibility Variants with Risks of Invasive Ovarian, Breast, and Colorectal Cancer
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Research Vol. 68, No. 21 ( 2008-11-01), p. 8837-8842
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 68, No. 21 ( 2008-11-01), p. 8837-8842
    Abstract: Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive ovarian, colorectal, and breast cancer. Twelve prostate cancer–associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04–1.37; Ptrend = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09–1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor allele OR, 0.95; 95% CI, 0.91–0.99; Ptrend = 0.028). This association was somewhat stronger for estrogen receptor–positive tumors (OR, 0.92; 95% CI, 0.87–0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies. [Cancer Res 2008;68(21):8837–42]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-08-2363
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 14
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    Acquisition and Persistence of Human Papillomavirus Infection in Younger Men: A Prospective Follow-up Study among Danish Soldiers
    American Association for Cancer Research (AACR) ; 2005
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 14, No. 6 ( 2005-06-01), p. 1528-1533
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 14, No. 6 ( 2005-06-01), p. 1528-1533
    Abstract: No data is yet available on incidence or persistence of human papillomavirus (HPV) infection in men. We enrolled 374 younger male conscripts (18-29 years) in a prospective study, and they were examined twice with an interval of 6 to 8 months. Data collection included a questionnaire and a sample of cells from the penis for HPV detection using PCR. In addition, the presence of Chlamydia trachomatis DNA was assessed in urine samples by means of PCR. The HPV prevalence at the first and second examinations was 33.8% and 31.9%, respectively. The acquisition rate of HPV (overall) during follow-up was 13.8%, and nearly one fourth of the participants were HPV positive at both examinations. Number of sex partners during follow-up was the most important risk factor for acquiring HPV (odds ratio, 17.2; 95% confidence interval, 4.6-64.7, for ≥3 partners versus ≤1 partner). In contrast, acquisition of a new HPV type in initially HPV-positive men was strongly related to having multiple HPV types at enrollment (OR, 4.1; 95% confidence interval, 1.4-12.3). This was also the most important risk factor for HPV persistence together with current smoking and having a high-risk HPV type at enrollment. This is the first study to assess risk factors for acquisition and persistence of HPV. The sexually transmitted nature of the infection is confirmed, and the data point to an important role of having multiple HPV types for persistence.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-04-0754
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
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  • 15
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    Polymorphism in the IL18 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 17, No. 12 ( 2008-12-01), p. 3567-3572
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 17, No. 12 ( 2008-12-01), p. 3567-3572
    Abstract: Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a & lt;25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567–72)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-08-0548
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 16
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    Effects of Common Germ-Line Genetic Variation in Cell Cycle Genes on Ovarian Cancer Survival
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 4 ( 2008-02-15), p. 1090-1095
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 4 ( 2008-02-15), p. 1090-1095
    Abstract: Purpose: Somatic alterations have been shown to correlate with ovarian cancer prognosis and survival, but less is known about the effects on survival of common inherited genetic variation. Of particular interest are genes involved in cell cycle pathways, which regulate cell division and could plausibly influence clinical characteristics of multiple tumors types. Experimental Design: We examined associations between common germ-line genetic variation in 14 genes involved in cell cycle pathway (CCND1, CCND2, CCND3, CCNE1, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CDK2, CDK4, CDK6, and RB1) and survival among women with invasive ovarian cancer participating in a multicenter case-control study from United Kingdom, Denmark, and United States. DNAs from up to 1,499 women were genotyped for 97 single-nucleotide polymorphisms that tagged the known common variants (minor allele frequency ≥0.05) in these genes. The genotypes of each polymorphism were tested for association with survival by Cox regression analysis. Results: A nominally statistically significant association between genotype and ovarian cancer survival was observed for polymorphisms in CCND2 and CCNE1. The per-allele hazard ratios (95% confidence intervals) were 1.16 (1.03-1.31; P = 0.02) for rs3217933, 1.14 (1.02-1.27; P = 0.024) for rs3217901, and 0.85 (0.73-1.00; P = 0.043) for rs3217862 in CCND2 and 1.39 (1.04-1.85; P = 0.033) for rs3218038 in CCNE1. However, these were not significant after adjusting for multiple hypothesis tests. Conclusion: It is unlikely that common variants in cell cycle pathways examined above associated with moderate effect in survival after diagnosis of ovarian cancer. Much larger studies will be needed to exclude common variants with small effects.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-1195
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 17
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    BRCA1 and BRCA2 Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 12 ( 2008-06-15), p. 3761-3767
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 12 ( 2008-06-15), p. 3761-3767
    Abstract: Purpose: To evaluate the prevalence of BRCA1 and BRCA2 mutations and associations with clinical correlates of disease in a population-based series of ovarian cancer cases from Denmark. Methods: DNA sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze the BRCA1 and BRCA2 genes for coding sequence mutations and large genomic rearrangements in 445 confirmed cases of ovarian cancer. We evaluated associations between mutation status and clinical characteristics, including cancer risks for first-degree relatives and clinicopathologic features of tumors. Results: Deleterious BRCA1 or BRCA2 mutations were identified in 26 cases; thus, mutations in these genes are responsible for at least 5.8% of ovarian cancer cases in this population. Five different mutations were identified in more than one individual, suggesting that they may be founder mutations in Denmark. We identified several differences between mutation carriers and noncarriers: mutation carriers were diagnosed at a significantly early age (median, 49 and 61 years, respectively; P = 0.0001); the frequency of BRCA1 mutation carriers was 23% for women diagnosed & lt;40 years, 15% for 40 to 49 years, 4% for 50 to 59 years, and 2% for ≥60 years (P = 0.00002); ovarian cancer in carriers was diagnosed at a later stage (P = 0.002) and tumors were of poorer grade (P = 0.0001); and first-degree relatives of mutation carriers had greater relative risks of both ovarian cancer [10.6 (95% confidence interval, 4.2-26.6); P & lt; 0.0001] and breast cancer & lt;60 years [8.7 (95% confidence interval, 3.0-25.0); P & lt; 0.0001]. Conclusion: These data may have a significant effect on risk assessment and clinical management of individuals from Denmark who are predisposed to ovarian cancer because they carry a BRCA1 or BRCA2 mutation.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-4806
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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    detail.hit.zdb_id: 2036787-9
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  • 18
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    Common Variants in RB1 Gene and Risk of Invasive Ovarian Cancer
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 20 ( 2006-10-15), p. 10220-10226
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 20 ( 2006-10-15), p. 10220-10226
    Abstract: Somatic alteration of the RB1 gene is common in several types of cancer, and germ-line variants are implicated in others. We have used a single nucleotide polymorphism (SNP) tagging approach to evaluate the association between common variants (SNP) in RB1 and risks of invasive ovarian cancer. We genotyped 11 tagging SNPs in three ovarian case-control studies from the United Kingdom, United States, and Denmark, comprising & gt;1500 cases and 4,800 controls. Two SNPs showed significant association with ovarian cancer risk: carriers of the minor allele of rs2854344 were at reduced risk compared with the common homozygotes [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.61-0.89; P = 0.0009 dominant model]. Similarly, the minor allele of rs4151620 was found to be associated with reduced risk (rare versus common homozygote; OR, 0.19; 95% CI, 0.07-0.53; P = 0.00005 recessive model). After adjusting for multiple testing, the most significant association (rs4151620) was P = 0.001. A global test comparing common haplotype frequencies in cases and controls was of borderline significance (P8df = 0.04). There are no common coding SNPs in the RB1 gene. However, intron 17 of RB1 contains the open reading frame for the P2RY5 gene, and rs4151620 is perfectly correlated with rs2227311, which is located in the 5′-untranslated region of P2RY5 and is predicted to affect P2RY5 transcription. rs2854344 has been reported previously to be associated with breast cancer risk. The possible associations of rs2854344 and rs4151620 with ovarian cancer risk warrant confirmation in independent case-control studies before studies on their biological mode of action. (Cancer Res 2006; 66(20): 10220-6)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-06-2222
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
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  • 19
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    Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 3 ( 2014-02-01), p. 852-861
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 3 ( 2014-02-01), p. 852-861
    Abstract: A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P & lt; 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-13-1051
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 20
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    Epidemiology and Natural History of Human Papillomavirus Infections and Type-Specific Implications in Cervical Neoplasia
    Elsevier BV ; 2008
    In:  Vaccine Vol. 26 ( 2008-8), p. K1-K16
    Details
    In: Vaccine, Elsevier BV, Vol. 26 ( 2008-8), p. K1-K16
    Type of Medium: Online Resource
    ISSN: 0264-410X
    URL: Article
    DOI: 10.1016/j.vaccine.2008.05.064
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2008
    detail.hit.zdb_id: 1468474-3
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