Block M.S.,Mayo Medical School |
Charbonneau B.,Mayo Medical School |
Vierkant R.A.,Health science Research |
Fogarty Z.,Health science Research |
And 96 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2014
Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-kB (NF-kB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-kB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10-5). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10-6] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10-5). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 ± 10-5) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10-4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. © 2014 American Association for Cancer Research.
Gasperin Jr. P.,Federal University of Paraná |
Tizzot E.L.A.,Federal University of Paraná |
Curcio Jr. L.,Federal University of Paraná |
Filho J.D.C.,State University Londrina |
And 6 more authors.
Journal of Lower Genital Tract Disease | Year: 2012
OBJECTIVE: This study aimed to compare cervical cancer screening by cervicography with screening by Pap test. MATERIALS AND METHODS: This was a comparative multicenter study of cervical cytology and cervicography. The cervicography (slides of the cervix) was taken after the Pap test was completed. In total, samples were collected from 1176 patients. Colposcopy with biopsy was considered the gold standard for the final diagnosis of lesions observed by the Pap test and cervicography. Statistical analysis was performed using the binomial test. RESULTS: In cases in which the Pap test was negative for cervical lesions, diagnosis by cervicography was positive in 15 cases of cervical intraepithelial neoplasia 1 (CIN 1) (p = .00052), in 1 case of CIN 2, in 1 case of CIN 3, and in 1 case of cancer. However, cervicography produced 3 false-positive results (p < .0001). CONCLUSIONS: Cervicography may be used as a complementary screening method to the Pap test for cervical cancer. © 2012, American Society for Colposcopy and Cervical Pathology.
PubMed | Danish Cancer Society, University of Houston, University of Southampton, Texas Southern University and 55 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2015
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 (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (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.
PubMed | Sloan Kettering Cancer Center, Gynecology Service, New York Medical College, Gynecologic Medical Oncology Service. and Computational Biology Program.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2014
BRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in high-grade serous ovarian cancer, we sought to evaluate the utility of BRCA1 immunohistochemistry (IHC) in screening for BRCA1 loss by germline, somatic, and epigenetic mechanisms.Patients with advanced high-grade serous ovarian cancer who had previously undergone germline BRCA1 testing were identified. Samples from each tumor were stained for BRCA1 and reviewed independently by two pathologists blinded to BRCA status. Tumors with abnormal BRCA1 IHC and wild-type germline testing underwent further evaluation for somatic BRCA1 mutations and promoter hypermethylation. McNemars test was used to determine the association of BRCA1 IHC with germline BRCA1 mutations and BRCA1 loss through any mechanism. Kaplan-Meier methods were used to estimate overall survival (OS), and the log-rank test was used to assess differences between groups.Inter-rater reliability between the two pathologists on BRCA IHC interpretation was very good (kappa coefficient 0.865, P = 0.16; McNemars test). BRCA1 IHC was abnormal in 36% (48/135) of cases. When compared with germline BRCA1 status, BRCA1 IHC had a high negative predictive value (95.4%) but a low positive predictive value (PPV, 52.1%). When accounting for promoter hypermethylation and somatic mutations as alternative methods of BRCA1 loss, the PPV rose to 87.5%. Five-year OS rate was 49.6% [95% confidence interval (CI) 26.3% to 69.3%] for patients with germline BRCA1 mutations, 50.4% (95% CI 27.5% to 69.5%) for germline wild-type BRCA1 and abnormal IHC, and 52.1% (95% CI 38.4% to 64.2%) for germline wild-type BRCA1 and normal IHC (P = 0.92).BRCA1 IHC interpretation was a highly reproducible and accurate modality for detecting germline, somatic, or epigenetic mechanisms of BRCA1 loss. These results support further development of BRCA1 IHC as a potential biomarker for BRCA1 loss in high-grade serous ovarian cancer.
Lilia Tena-Suck M.,Instituto Nacional Of Neurologia Y Neurocirugia |
Alarcon-Herrera A.,Gynecology Service |
Tirado-Sanchez A.,Hospital General Of Mexico |
Rosl F.,Deutsches Krebsforschungzentrum |
La Vega H.A.-D.,Oncology Hospital
Diagnostic Cytopathology | Year: 2012
The aims of this study were to determine HPV in a male population and its correlation with penile gross inspection and urethral pap smears. Fifty male volunteers were included in the study; all of them were sexual partners of women with evidence of HPV-related cervical diseases. Urethral Pap smear features and polymerase chain reaction (PCR; HPV detection) of urethral samples were correlated. Statistical analyses were conducted to identify variables associated with high and low-risk HPV types. Mean age of participants was 33.14 ± 1.52 (range, 23-50 years), and the mean age for those with high risk HPV was 32.12 ± 6.66 and 34.08 ± 6.58 for subjects with low-risk HPV (P = 0.820). Penile gross inspection revealed 19 (38%) cases with no lesions, papules in balanoprepusial furrol/sulcus in 23 (46%) cases, papilla in 23 (46%) cases, urethral lesions in 22 (44%) cases, penile body plaques in 22 (44%) cases, melanoses in 11 (22%) cases, sebaceous cysts on scrotum in 10 (20%) cases, and molting of the glands in 28 (56%) cases. Cytopathologic analysis revealed koilocytes in 24 (48%) cases. Dyskeratosis was observed in 24 (48%) cases. A bacterial background was found in 27 (54%) cases, and inflammatory cells were found in 27 (54%) cases. Twenty-six (52%) cases showed cytological features suggestive of Gardnerella Vaginalis. Twenty-four (48%) cases were high-risk HPV, and 26 (52%) were low-risk HPV (P = 0.037) as assessed by PCR-based detection. There was a statistically significant difference between koilocytes and bacterial background with high-risk human papillomavirus (P = 0.001). Abnormal colposcopy examination detected lesions were sampled for cytology by Pap smears. Copyright © 2011 Wiley Periodicals, Inc.