Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk1. We performed a genome wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and ~2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P<10−8). The most significant SNP (rs3814113; P = 2.5 × 10−17) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls confirming its association (combined data odds ratio = 0.82 95% CI 0.79 – 0.86, P-trend = 5.1 × 10−19). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77 95% CI 0.73 – 0.81, Ptrend = 4.1 × 10−21).

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Objectives: The aim of the study was to examine the overall risk factors for epithelial ovarian cancer and according to histologic subtypes. Materials and Methods: Ovarian cancer cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. A total of 554 cases and 1,564 randomly selected controls were included. The analyses were done using multiple logistic regression models. Results: The overall risk of ovarian cancer decreased with ever being pregnant [odds ratios (OR), 0.40; 95% confidence intervals (CI), 0.30-0.55], with increasing pregnancies (OR, 0.63; 95% CI, 0.45-0.87 and OR, 0.51; 95% CI, 0.37-0.69 for two and three pregnancies as compared with one), and with older age at first and last pregnancy, respectively. Increasing years of ovulation was a very strong risk factor with a 7% to 8% increase in risk for each year of ovulation. Use of oral contraceptives (OR, 0.67, 95% CI, 0.53-0.85) and longer duration of use were associated with a decreased risk of ovarian cancer. Ever use of hormone replacement therapy increased the overall risk (OR, 1.30; 95% CI, 1.05-1.61). For all those variables, the effect was present for serous tumors, endometrioid tumors, and tumors of other histologies, but not for mucinous tumors. In contrast, current smoking was a risk factor only for mucinous tumors (OR, 1.78; 95% CI, 1.01-3.15) and increasing body mass index tended to increase the risk especially for mucinous and endometrioid tumors. Conclusions: We confirmed already known risk factors for ovarian cancer, and we observed significant differences in the risk profiles between mucinous and nonmucinous tumors indicating different etiologies. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1160 -6)

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BackgroundStudies comparing self-samples and clinician-collected samples for high-risk human papillomavirus (HPV) detection using clinically validated PCR-based HPV DNA assays are limited. We measured the concordance of HPV detection between home-based self-sampling and general practitioner (GP) sampling using the Cobas 4800 HPV DNA test and studied women’s accept of home-based self-sampling.MethodsPaired GP-collected samples and cervico-vaginal self-samples were obtained from 213 women aged 30–59 years diagnosed with ASC-US within the cervical cancer screening program. After undergoing cervical cytology at their GP, the women collected a self-sample with the Evalyn Brush at home and completed a questionnaire. Both samples were HPV-tested using the Cobas 4800 test. Histology results were available for those who tested HPV positive in GP-collected samples.ResultsWe observed good concordance for HPV detection between self-samples and GP-collected samples (κ: 0.70, 95% CI: 0.58–0.81). No underlying CIN2+ cases were missed by self-sampling. Women evaluated that self-sampling was easy (97.2%, 95% CI: 93.9–98.9%) and comfortable (94.8%, 95% CI: 90.9–97.4%).ConclusionsHome-based self-sampling using the Evalyn Brush and the Cobas 4800 test is an applicable and reliable alternative to GP-sampling.

BACKGROUNDThe HER‐2 (Human Epidermal Growth factor receptor‐2, also known as c‐erb‐2/neu) protooncogene encodes a transmembrane receptor protein, Mr 185,000. Studies have shown that the HER‐2 oncogene is overexpressed in approximately 25–30% of ovarian carcinoma (OC) cases, but to the authors' knowledge, to date no consensus regarding overexpression and prognosis has been possible. The objective of the current study was first to analyze the presence of HER‐2 overexpression in tissue from Danish OC patients and correlate the distribution of HER‐2 overexpression with clinical and biochemical data and second to investigate the value of HER‐2 overexpression as a prognostic marker in OC and to compare this value with the prognostic value of other biochemical markers.METHODSThe study population was comprised of the first 181 patients diagnosed with epithelial OC who were included in the MALOVA study. The staining procedure for HER‐2 overexpression was performed using the p185 antibody.RESULTSHER‐2 overexpression was found in 95 of the 181 investigated cases (52.5%), in which 71 carcinomas (39.2%) were weakly positive (1+) and 24 carcinomas (13.3%) were moderately (2+) to intensely positive (3+). Increased HER‐2 expression was found to be correlated with reduced survival. Significant differences in survival between patients with (1+, 2+, and 3+) and those without HER‐2 overexpression were found for patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I, Stage III, and Stage III/IV OC (Stage I: P = 0.021; Stage III: P = 0.0078; and Stage III/IV: P = 0.0054). Multivariate survival analyses including all 181 OC patients demonstrated that HER‐2 overexpression is a prognostic marker (P = 0.003) together with disease stage, serum tetranectin level, and patient age. For patients with Stage III OC, the only independent prognostic factors detected were HER‐2 overexpression (P = 0.009) and serum tetranectin level (P ≤ 0.0001).CONCLUSIONSThe results of the current study show that HER‐2 overexpression has prognostic value both in univariate and multivariate survival analyses. Therefore, the clinical relevance of this observation should be established conclusively by therapy that targets HER‐2 in a prospective Phase II clinical trial. Cancer 2003;98:66–73. © 2003 American Cancer Society.DOI 10.1002/cncr.11476

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BackgroundCervical cancer screening participation remains insufficient in most countries. Our aim was to evaluate whether offering a HPV self-sampling kit, either mailed directly to the woman’s home or using timely opt-in procedures for ordering the kit, increased screening participation compared with a standard second reminder.MethodsIn this randomized, controlled effectiveness trial, 9791 Danish women aged 30–64 who were due to receive the second reminder were equally randomized to either: 1) direct mailing of a second reminder and a self-sampling kit (directly mailed group); 2) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail, text message, phone, or webpage (opt-in group); or 3) mailing of a second reminder to attend regular cytology screening (control group). In an intention-to-treat analysis, we estimated the participation rate at 180 days post intervention, by returning a self-sample or attending regular cytology screening. We calculated the proportion of women with a positive HPV self-sample who attended for cervical cytology triage at the general practitioner within 90 days.ResultsParticipation was significantly higher in the directly mailed group (38.0%) and in the opt-in group (30.9%) than in the control group (25.2%) (participation difference (PD): 12.8%, 95% CI: 10.6–15.0% and PD: 5.7%, 95% CI: 3.5–7.9%, respectively). Within 90 days, 107 women (90.7%, 95% CI: 83.9–95.3%) with a HPV-positive self-sample attended follow-up.ConclusionsOffering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation; the direct mailing strategy was the most effective invitation strategy. A high compliance with follow-up was seen.Trial registrationCurrent Controlled Trials NCT02680262. Registered 10 February 2016.