Polymorphisms of GSTP1 and related genes and prostate cancer risk.

Glutathione S-transferase P1 (GSTP1) is markedly downregulated in prostate cancer and prostatic intraepithelial neoplasia compared to normal prostate tissue. Downregulation of GSTP1 may, therefore, be an early event in prostate carcinogenesis. An A-->G polymorphism at nucleotide 313 results in an amino acid substitution (Ile105Val) in the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. In a study of 36 prostate cancer patients, Harries et al. reported that the Ile/Ile genotype is associated with a decreased risk of prostate cancer (odds ratio 0.4 (0.17-0.82)). We sought to confirm this finding and to examine the impact of this polymorphism together with several related polymorphisms implicated as risk factors for carcinogen-associated malignancies. One hundred and seventeen patients with prostate adenocarcinoma and 183 population-based controls were recruited to this case-control study. Genotyping of the GSTP1 (Ile105Val), GSTM1 (null), GSTT1 (null) and CYP1A1 (Ile462Val) genes was performed using polymerase chain reaction (PCR) based techniques on DNA prepared from peripheral blood. A questionnaire was used to collect demographic information from each subject. Cases were significantly older (P<0.0001) and had significantly greater family history of prostate cancer (P<0.0001), confirming known risk factors for this disease. By chi(2) analysis, none of the genotype distributions varied among cases and controls. Using a logistic regression model to control for known risk factors we were also unable to demonstrate a significant association with prostate cancer for any of the polymorphisms tested. This population fails to identify a relationship between the above polymorphisms and prostate adenocarcinoma.

Genetic polymorphisms in head and neck cancer risk.

OBJECTIVE: To assess whether genetic polymorphisms implicated as risk factors for other tobacco-associated malignancies are associated with altered risk of head and neck squamous cell carcinoma. DESIGN: Case-control study. SUBJECTS: One hundred sixty patients with head and neck squamous cell carcinoma recruited from a university-based head and neck oncology clinic and 149 population-based controls. METHODS: Genotyping of the CYP1A1 (Ile462Val), GSTM1 (null), GSTP1 (Ile105Val), GSTT1 (null), and P53 (Arg72Pro) genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. In addition, a questionnaire was used to collect demographic information from each subject. RESULTS: Cases were significantly older (p <.0001) and had significantly greater tobacco use (p <.0001) and were more likely to be male (p <.0001) than were control subjects, thus confirming known risk factors for this disease. When cases and controls were compared by simple chi-square analysis, only the frequency of CYP1A1 (Ile462Val) polymorphism was significantly different between cases and controls (OR =.42; 95% CI =.18-.99; p <.04). However, with a logistic regression model to control for known risk factors, we were unable to demonstrate a significant association with head and neck cancer for any of the polymorphisms tested, including CYP1A1. CONCLUSIONS: This population fails to identify a relationship between the above-mentioned polymorphisms and head and neck cancer.

Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk.

The association between glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk has been controversial in the published literature. To examine this controversy, 12 case-control studies of GSTM1 status and lung cancer risk were identified in the published English literature. These studies included a total of 1593 cases and 2135 controls. We conclude that GSTM1 deficiency is a moderate risk factor for lung cancer development with an odds ratio of 1.41 (95% confidence interval = 1.23-1.61; P < 0.0001) by using Mantel-Haenszel methods for stratified analysis. This increased risk is evident for all the major histological subtypes of lung cancer. Although the increased risk is small, GSTM1 deficiency accounts for approximately 17% of lung cancer cases because of the high prevalence of GSTM1 deficiency.

HEC consortium survey: current perspectives of physicians and nurses.

At the request of the Midwest Bioethics Center (MBC), we surveyed nurses' and physicians' attitudes and needs regarding Hospital Ethics Committees (HECs). The primary objective of this research project was to inform the practices and policies of the Ethics Committee Consortium of the Bioethics Center. Four thousand eight hundred and twenty-nine surveys were distributed to the medical and nursing staff of eight Kansas City metropolitan area hospitals. One thousand and fifty-five surveys were returned, representing a response rate of 21%. This survey examined five areas believed to be related to nurse and physician use of and participation on HECs: [1] Training in Biomedical Ethics; [2] Nature and Purpose of HECs; [3] HEC Functions-Case Consultation; [4] Ethical Decision-Making and Patient Care; and [5] Continuing Education. Important findings include lack of knowledge regarding whether case review is required or optional, and whether recommendations are binding or advisory; a perception that training in medical ethics was inadequate; and a strong indication that HECs should be accessible. These findings are consistent with and extend the findings of prior descriptive research in this area.