Case-control study on occupational risk factors for soft-tissue sarcoma.

OBJECTIVE: The main objective of this study was to investigate potential association between development of soft-tissue sarcoma (STS) and occupational exposures related to farming and the agricultural industry in Canada. METHODOLOGY: A population-based case-control study of STS was conducted among Canadian men stratified by province of residence and age group. Conditional logistic regression was used to fit multivariable statistical models. RESULTS: The following variables were positively associated with the incidence of STS: machinist, chicken farming, pulp and paper industry worker, and apartment complex worker. Mixed farming and exposure to chlorine were negatively associated with STS. CONCLUSION: The higher risk of developing STS may be associated with longest-held job as a machinist, short-term jobs as chicken farm worker, pulp and paper industry worker, and apartment complex worker.

Optimally-connected hidden markov models for predicting MHC-binding peptides.

Hidden Markov models (HMMs) are one of various methods that have been applied to prediction of major histo-compatibility complex (MHC) binding peptide. In terms of model topology, a fully-connected HMM (fcHMM) has the greatest potential to predict binders, at the cost of intensive computation. While a profile HMM (pHMM) performs dramatically fewer computations, it potentially merges overlapping patterns into one which results in some patterns being missed. In a profile HMM a state corresponds to a position on a peptide while in an fcHMM a state has no specific biological meaning. This work proposes optimally-connected HMMs (ocHMMs), which do not merge overlapping patterns and yet, by performing topological reductions, a model's connectivity is greatly reduced from an fcHMM. The parameters of ocHMMs are initialized using a novel amino acid grouping approach called "multiple property grouping." Each group represents a state in an ocHMM. The proposed ocHMMs are compared to a pHMM implementation using HMMER, based on performance tests on two MHC alleles HLA (Human Leukocyte Antigen)-A*0201 and HLA-B*3501. The results show that the heuristic approaches can be adjusted to make an ocHMM achieve higher predictive accuracy than HMMER. Hence, such obtained ocHMMs are worthy of trial for predicting MHC-binding peptides.

Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen.

Tamoxifen treatment substantially improves the 10-year survival of women with estrogen-receptor (ER)-alpha-positive tumors. However, approximately one-third of all breast cancer patients with ER-alpha-positive tumors progress on antiestrogen therapy. The molecular mechanism(s) involved in antiestrogen-resistant phenotype of breast carcinoma is not completely understood. The PTEN (phosphatase and tensin homolog deleted on chromosome Ten) gene is a novel candidate tumor suppressor that plays an important role in cell cycle regulation and apoptosis by regulating Protein kinase-B/Akt activity. Previous studies have shown that PTEN downregulation in breast cancer is associated with high-grade tumor, distant metastases and poorer disease-free survival. Decreased PTEN and/or increased protein kinase B/Akt activity in breast cancer cells has recently been associated with resistance to tamoxifen-induced apoptosis. In this study, we have evaluated PTEN expression by immunohistochemistry in 100 tamoxifen-treated ER-alpha-positive breast cancer patients. Reduced PTEN protein expression was associated with shorter relapse-free survival. When stage I patients were analyzed separately, reduced PTEN expression was a strong predictor of both, shorter relapse-free survival and shorter disease-specific survival. An association of reduced PTEN expression with shorter relapse-free survival and disease-specific survival in stage I patients was still observed after stratification by stage, axillary lymph node status, tumor size, grade, and expression of ER-alpha, progesterone receptor, and Her-2/neu. In summary, our results showed a strong association between downregulation of PTEN expression in ER-alpha-positive tumors and failure to tamoxifen treatment.