The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV). Although the incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, particularly cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-α) cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. Therefore the aim of the study was to investigate the allelic distribution of -308 TNF-α gene polymorphism in South African women with cervical cancer compared to control women.</p> <p>Methods</p> <p>Included in our study were women with histologically proven cancer of the cervix (n = 244) and hospital-based controls (n = 228). All patients and controls were from mixed race and black population groups in South Africa. The detection of a bi-allelic -308 (A/G) polymorphism in the promoter region of TNF-α was investigated using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups.</p> <p>Results</p> <p>In this study we observed no association between the distribution of -308 TNF-α polymorphism and the risk of developing cervical cancer even after combining the data from the two ethnic populations (X²= 2.26). In addition, using the chi-squared test we found no significant association between the known risk factors for cervical cancer and the allele distribution of -308 TNF-α. However, the frequency of the rare high-producing allele -308A of TNF-α was significantly lower in the South African population when compared to Caucasians and Chinese population groups.</p> <p>Conclusion</p> <p>We demonstrated no association between -308 TNF-α polymorphism and the risk of cervical cancer among two South African ethnic population groups. However, as the distribution of the -308A TNF-α was notably different between the control groups of South Africa and other population groups this result suggests that ethnic disparity may influence the levels of TNF-α produced.</p

Prescribing Quality in Older Veterans: A Multifocal Approach

BACKGROUND AND OBJECTIVE: Quality prescribing for older adults involves multiple considerations. We evaluated multiple aspects of prescribing quality in older veterans to develop an integrated view of prescribing problems and to understand how the prevalence of these problems varies across clinically important subgroups of older adults. DESIGN AND PARTICIPANTS: Cross-sectional observational study of veterans age 65 years and older who received medications from Department of Veterans Affairs (VA) pharmacies in 2007. MAIN MEASURES: Using VA pharmacy data linked with encounter, laboratory and other data, we assessed five types of prescribing problems. KEY RESULTS: Among 462,405 patients age 65 and older, mean age was 75 years, 98 % were male, and patients were prescribed a median of five medications. Half of patients (50 %) had one or more prescribing problems, including 12 % taking one or more medications at an inappropriately high dose, 30 % with drug–drug interactions, 3 % with drug–disease interactions, and 26 % taking one or more Beers criteria drugs. In addition, 16 % were taking a high-risk drug (warfarin, insulin, and/or digoxin). On multivariable analysis, age was not strongly associated with four of the five types of prescribing issues assessed (relative risk < 1.3 across age groups), and comorbid burden conferred substantially increased risk only for drug–disease interactions and use of high-risk drugs. In contrast, the number of drugs used was consistently the strongest predictor of prescribing problems. Patients in the highest quartile of medication use had 6.6-fold to12.5-fold greater risk of each type of prescribing problem compared to patients in the lowest quartile (P < 0.001 for each). CONCLUSIONS: The number of medications used is by far the strongest risk factor for each of five types of prescribing problems. Efforts to improve prescribing should especially target patients taking multiple medications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-014-2924-8) contains supplementary material, which is available to authorized users