Retrospective Validation

Paper: Systematic evaluation of candidate blood markers for detecting ovarian cancer.

"BACKGROUND: Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging.

Paper: The SRD5A2 V89L polymorphism is associated with severity of disease in men with early onset prostate cancer.

"BACKGROUND: Emerging evidence indicates that testosterone (T), and not dihydrotestosterone (DHT), is the most relevant androgen that promotes carcinogenesis in the prostate. Steroid 5-alpha reductase type II (SRD5A2) catalyzes the irreversible conversion of T to DHT in male reproductive organs. Because the SRD5A2 gene is highly polymorphic at codon 89, two SRD5A2 isoforms are expressed that differ in K(m) and V(max) values. The more common and rapid catalytic isoform contains a valine residue at position 89; the slower-catalytic variant contains leucine at this position.

Paper: "Multiple loci identified in a genome-wide association study of prostate cancer Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholde

"We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study, by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci [two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)].

Paper: Screening for small-cell lung cancer: a follow-up study of patients with Lambert-Eaton myasthenic syndrome.

"PURPOSE: A small-cell lung carcinoma (SCLC) is found in 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS). We evaluated screening to optimize screening strategy for SCLC. It is important to detect these tumors early in newly diagnosed patients with LEMS to offer optimal patient treatment.

Paper: Plasma DNA Quantification in Lung Cancer CT Screening: 5-years Results of a Prospective Study.

"Rationale. Free circulating plasma DNA has emerged as a potential biomarker for early lung cancer detection. In a previous case-control study we have shown that high levels of plasma DNA are a strong risk factor for lung cancer. Objective. To assess the diagnostic performance and prognostic value of plasma DNA levels in a cohort of 1035 heavy smokers monitored by annual spiral-CT for 5 years. Methods. Plasma DNA levels were determined through real-time quantitative PCR at baseline and at time of lung cancer diagnosis.

Paper: Prediction of ovarian cancer prognosis and response to chemotherapy by a serum-based multiparametric biomarker panel.

"Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ovarian cancer patients were collected prior and during chemotherapy and were analysed by enzyme-linked immunosorbent assay for CA125, kallikreins 5, 6, 7, 8, 10 and 11, B7-H4, regenerating protein IV and Spondin-2.

Paper: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases.

"Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively.

Paper: Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma.

"BACKGROUND: Hypermethylation of the RASSF1A [Ras association (RalGDS/AF-6) domain family member 1A] gene is frequently observed in hepatocellular carcinoma (HCC). We evaluated the analysis of circulating hypermethylated RASSF1A for detecting HCC and assessing its prognosis. METHODS: In module 1, we studied 63 pairs of HCC patients and age- and sex-matched chronic hepatitis B virus (HBV) carriers, as well as 50 healthy volunteers. In module 2, we studied 22 HCC patients with cancer detected through a surveillance program.

Paper: "The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PL

"OBJECTIVE: To determine the epidemiology of CA-125 in women without ovarian cancer. METHODS: We analyzed demographic, medical and lifestyle characteristics related to CA-125, measured using the Centocor CA-125II RIA assay, among 25,608 multi-ethnic U.S. women aged 55-74 years enrolled in a cancer screening trial and found to have no evidence of ovarian cancer. RESULTS: Mean CA-125 level was 11.9 U/ml (SD 8.3); median 10.0 U/ml, interquartile range 8.0-14.0.

Paper: Predicting Prostate Cancer Risk Through Incorporation of Prostate Cancer Gene 3.

"PURPOSE: The online Prostate Cancer Prevention Trial risk calculator combines prostate specific antigen, digital rectal examination, family and biopsy history, age and race to determine the risk of prostate cancer. In this report we incorporate the biomarker prostate cancer gene 3 into the Prostate Cancer Prevention Trial risk calculator. MATERIALS AND METHODS: Methodology was developed to incorporate new markers for prostate cancer into the Prostate Cancer Prevention Trial risk calculator based on likelihood ratios calculated from separate case control or cohort studies.

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