Identifying Biomarkers from Mass Spectrometry Data with Ordinal Outcome

In recent years, there has been an increased interest in using protein mass spectroscopy to identify molecular markers that discriminate diseased from healthy individuals. Existing methods are tailored towards classifying observations into nominal categories. Sometimes, however, the outcome of interest may be measured on an ordered scale. Ignoring this natural ordering results in some loss of information. In this paper, we propose a Bayesian model for the analysis of mass spectrometry data with ordered outcome. The method provides a unified approach for identifying relevant markers and predicting class membership. This is accomplished by building a stochastic search variable selection method within an ordinal outcome model. We apply the methodology to mass spectrometry data on ovarian cancer cases and healthy individuals. We also utilize wavelet-based techniques to remove noise from the mass spectra prior to analysis. We identify protein markers associated with being healthy, having low grade ovarian cancer, or being a high grade case. For comparison, we repeated the analysis using conventional classification procedures and found improved predictive accuracy with our method

Thrombosis is associated with inferior survival in multiple myeloma.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Patients with multiple myeloma are at an increased risk of venous thromboembolism and arterial thrombosis. We assessed the impact of venous and arterial thrombosis on survival in a population-based study of 9,399 multiple myeloma patients diagnosed in Sweden from 1987 to 2005. We found multiple myeloma patients with venous thromboembolism to have a higher mortality at 1-, 5-, and 10-years of follow up compared with those without, with hazard ratios of 2.9 (95% confidence interval (CI) 2.4-3.5), 1.6 (95% CI: 1.5-1.8), and 1.6 (95% CI: 1.4-1.7), respectively. There was an increase in risk of death among multiple myeloma patients with arterial thrombosis, with hazard ratios of 3.4 (95% CI: 3.0-3.8), 2.2 (95% CI: 2.0-2.3), and 2.1 (95% CI: 1.9-2.1), respectively. In landmark analyses at six months, early arterial but not venous thromboembolism was associated with a higher risk of death. Thus, in contrast to prior smaller studies, we found the development of thrombosis to be associated with significantly poorer survival. The prevention of thrombosis in multiple myeloma is an important goal in the management of these patients.regional agreement on medical training and clinical research (ALF) between Stockholm County Council regional agreement on medical training and clinical research (ALF) between Karolinska Institutet Cancer Society in Stockholm Intramural Research Program of the NIH, NC

Menopausal hormone therapy and risk of biliary tract cancers

Funding: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The funders had no role in the conduct of this research.Peer reviewedPostprintsupplementary_dat

Association between aspirin use and biliary tract cancer survival

Peer reviewedPublisher PD

Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men

Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.In 728 Swedish cases of monoclonal gammopathy of undetermined significance (MGUS), followed up to 30 years (median, 10 years), we estimated the cumulative risk of hematologic disorders originating from lymphoid and myeloid lineages. Using Cox regression models, we examined associations of demographic and laboratory factors with progression and determined the discriminatory power of 3 prediction models for progression. Eighty-four MGUS cases developed a lymphoid disorder, representing a cumulative risk of 15.4%. Multiple myeloma (MM) occurred in 53 patients, and the 30-year cumulative risk was 10.6%; an ∼0.5% annual risk. Three factors were significantly associated with progression: abnormal free light-chain (FLC) ratio (1.65), M-protein concentration (≥1.5 g/dL), and reduction of 1 or 2 noninvolved immunoglobulin isotype levels (immunoparesis). A prediction model with separate effects for these 3 factors and the M-protein isotype had higher discriminatory power than other models, although the differences were not statistically significant. The 30-year cumulative risk for myeloid malignancies was 1.5 g/dL, factors previously considered by Mayo Clinic researchers, are predictors for MM progression and suggests that separate consideration of immunoparesis and the Mayo Clinic risk factors could improve identification of MGUS patients at high risk for progression

Associations Between Cancer and Alzheimer\u27s Disease in a U.S. Medicare Population: Case-control and Cohort Studies

Several studies have reported bidirectional inverse associations between cancer and Alzheimer\u27s disease (AD). This study evaluates these relationships in a Medicare population. Using Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data, 1992-2005, we evaluated cancer risks following AD in a case-control study of 836,947 cancer cases and 142,869 controls as well as AD risk after cancer in 742,809 cancer patients and a non-cancer group of 420,518. We applied unconditional logistic regression to estimate odds ratios (ORs) and Cox proportional hazards models to estimate hazards ratios (HRs). We also evaluated cancer in relation to automobile injuries as a negative control to explore potential study biases. In the case-control analysis, cancer cases were less likely to have a prior diagnosis of AD than controls (OR = 0.86; 95% CI = 0.81-0.92). Cancer cases were also less likely than controls to have prior injuries from automobile accidents to the same degree (OR = 0.83; 95% CI = 0.78-0.88). In the prospective cohort, there was a lower risk observed in cancer survivors, HR = 0.87 (95% CI = 0.84-0.90). In contrast, there was no association between cancer diagnosis and subsequent automobile accident injuries (HR = 1.03; 95% CI = 0.98-1.07). That cancer risks were similarly reduced after both AD and automobile injuries suggest biases against detecting cancer in persons with unrelated medical conditions. The modestly lower AD risk in cancer survivors may reflect underdiagnosis of AD in those with a serious illness. This study does not support a relationship between cancer and AD