Epidemiological and clinical aspects of nonsteroidal anti-inflammatory drugs and cancer risks.

It is well known that about 70% of cancer cases are due to environmental, dietary, or lifestyle factors. Accordingly, these cases maybe avoided by appropriate modifications. In addition, active chemoprevention has become a major interventional approach following the epidemiological observation of a beneficial effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in colon cancer prevention. This is chiefly due to the inhibition of the cyclooxygenase (COX) enzymes. The COX enzymatic system includes two isoenzymes, COX-1 and COX-2, that convert arachidonic acid to prostaglandins. COX-1 is constitutively expressed and synthesizes cytoprotective prostaglandins in the gastrointestinal tract. COX-2 is inducible by the oncogenes ras and scr and other cytokines; it is overexpressed in human cancer cells in which it stimulates cellular division and angiogenesis and inhibits apoptosis. NSAIDs restore apoptosis and decrease tumor mitogenesis and angiogenesis. Most cancer cells have been found to exhibit overexpression of COX-2. Epidemiological studies showed a lower risk of developing cancer of the colon, breast, esophagus, and stomach following the ingestion of NSAIDs. The use of NSAIDs in low dose was associated with a statistically significant decrease in the risk of adenomatous polyps and of overt colon cancer. The regressive effects of sulindac on foci of aberrant crypts in the colon (considered to be precursors of adenoma), and on adenocarcinoma of the colon, are of particular interest because this NSAID does not have an inhibitory effect on COX. This may support the view that the antineoplastic effect of NSAIDs may also be due to a mechanism other than COX-2 inhibition. In breast cancer, large cohort studies reported a 40 to 50% reduced risk of developing cancer, a smaller size of the primary tumor, and a reduction in the number of involved axillary lymph nodes. Similar findings have been reported in the esophagus and stomach, but not in gastric cardia adenocarcinoma. The recent development of selective COX-2 inhibitors resulted in better clinical tolerance than that associated with NSAIDs in general, with the absence of gastrointestinal side effects known to occur after the inhibition of COX-1. Encouraging results have been obtained with these new agents in familial adenomatous polyposis, colon, breast, and prostate cancer.

A pilot study of male breast cancer in the Veterans Affairs healthcare system.

BACKGROUND: We report our findings on a hospital-based retrospective pilot cohort with case-controls study, which we carried out to examine genetic, environmental, and occupational risk factors in men with breast cancer. METHODS: 86 men with breast cancer were diagnosed in eight VA medical centers that agreed to collaborate on this project. A case-control analysis was conducted on a subset of the male breast cancer cases (n = 44) and age- and ethnicity-matched controls (n = 77). We compared host characteristics, comorbidities, and medications intake between cases and controls by using Chi-square analysis and Fisher's exact test. RESULTS: The descriptive analysis showed that the majority of veterans with male breast cancer were non-Hispanic white (60%), older than 65 years at diagnosis (56%), and more likely estrogen receptor positive (45%). World War II veterans represented the largest group (22%), followed by the Vietnam era veterans (10%). Thirty-three percent reported a positive family history of cancer, while 18% had another primary cancer diagnosis. Prior alcohol (43%) and tobacco use (56%) was substantial among these patients. Twenty percent of patients were overweight or obese and 55% had comorbid diseases with heart disease being the most prevalent, followed by diabetes mellitus. The case-control analysis yielded a significantly greater proportion of cases with gynecomastia (p < 0.0001), a positive family history of cancer (p = 0.0028), history of antibiotic use (p = 0.0112), and history of tobacco use (p = 0.0143) compared to controls. CONCLUSION: The findings of this hospital-based pilot study indicate case-control differences in gynecomastia and family history of cancer. The pilot study lacked sufficient power to determine a true association between the variables of interest and warrants a large-scale collaborative study between the VA medical centers.

Quality of life after a diagnosis of prostate cancer among men of lower socioeconomic status: results from the Veterans Affairs Cancer of the Prostate Outcomes Study.

OBJECTIVES: To evaluate prospectively the health-related and disease-specific quality of life (QOL) at diagnosis and during the first year thereafter for patients with newly diagnosed prostate cancer who received care at Veterans Affairs Medical Centers. METHODS: Interviewers administered the European Organization for Research and Treatment of Cancer-QOL Questionnaire, a valid and reliable measure of health status, to 140 patients with prostate cancer at baseline (at diagnosis, before the initiation of treatment) and at 3 and 12 months thereafter at five Veterans Affairs Medical Centers. The mean changes from baseline values were analyzed statistically for patients with localized disease stratified by treatment group and separately for patients with metastatic disease. RESULTS: Among the 98 men with localized prostate cancer, significant disease-specific QOL changes noted at 3 and 12 months included worsening of urinary and sexual function among men treated with radical prostatectomy or radiotherapy and worsening of urinary function among those who opted for watchful waiting (each P <0.05). Among the 42 men with metastatic prostate cancer, significant decrements in role and social and sexual function were noted at 3 months, but had resolved on average by 12 months of follow-up. CONCLUSIONS: At 12 months, disease-specific QOL decrements persisted for patients with localized disease, but for patients with metastatic disease, disease-specific QOL appeared to return to near baseline (at diagnosis, before treatment initiation) function. Our study, among the first to assess the QOL at baseline before treatment, provides meaningful information on general treatment effects, which are directly relevant to clinicians when discussing treatment options with patients.