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Biomedical subjects

Randall E Harris

Publications and source records attributed to Randall E Harris.

9 recordsLinked to original sources
PubMed2006

Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors.

BACKGROUND: Epidemiologic and laboratory investigations suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against breast cancer due to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of breast cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 323 incident breast cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003-2004 and compared with 649 cancer free controls matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and breast cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR) and 95% confidence intervals. RESULTS: Results showed significant risk reductions for selective COX-2 inhibitors as a group (OR = 0.29, 95% CI = 0.14-0.59), regular aspirin (OR = 0.49, 95% CI = 0.26-0.94), and ibuprofen or naproxen (0.36, 95% CI = 0.18-0.72). Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg) produced no significant change in the risk of breast cancer. CONCLUSION: Selective COX-2 inhibitors (celecoxib and rofecoxib) were only recently approved for use in 1999, and rofecoxib (Vioxx) was withdrawn from the marketplace in 2004. Nevertheless, even in the short window of exposure to these compounds, the selective COX-2 inhibitors produced a significant (71%) reduction in the risk of breast cancer, underscoring their strong potential for breast cancer chemoprevention.

Adult↗
PubMed2005

Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review).

We comprehensively reviewed the published scientific literature on non-steroidal anti-inflammatory drugs (NSAIDs) and cancer and evaluated results based upon epidemiologic criteria of judgment: consistency of results, strength of association, dose response, molecular specificity, and biological plausibility. Sufficient data from 91 epidemiologic studies were available to examine the dose response of relative risk and level of NSAID intake for ten human malignancies. Dose response curves were fitted by exponential regression. Results showed a significant exponential decline in the risk with increasing intake of NSAIDs (primarily aspirin or ibuprofen) for 7-10 malignancies including the four major types: colon, breast, lung, and prostate cancer. Daily intake of NSAIDs, primarily aspirin, produced risk reductions of 63% for colon, 39% for breast, 36% for lung, and 39% for prostate cancer. Significant risk reductions were also observed for esophageal (73%), stomach (62%), and ovarian cancer (47%). NSAID effects became apparent after five or more years of use and were stronger with longer duration. Observed protective effects were also consistently stronger for gastrointestinal malignancies (esophagus, stomach, and colon). Results for pancreatic, urinary bladder, and renal cancer were inconsistent. Initial epidemiologic studies of malignant melanoma, Hodgkin's disease, and adult leukemia also found that NSAIDs are protective. A few studies suggest that ibuprofen has stronger anticancer effects than aspirin, particularly against breast and lung cancer. Overexpression of cyclooxygenase-2 (COX-2) and increased prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most anatomic sites. Preclinical investigations provide consistent evidence that both selective and non-selective NSAIDs effectively inhibit chemically-induced carcinogenesis of epithelial tumors. This review provides compelling and converging evidence that regular intake of NSAIDs that non-selectively block COX-2 protects against the development of many types of cancer.

Animals↗
PubMed2003

Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative.

We analyzed data from the prospective Women's Health Initiative (WHI) Observational Study to examine the effects of regular use of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer risk. We studied a population of 80,741 postmenopausal women between 50 and 79 years of age who reported no history of breast cancer or other cancers (excluding nonmelanoma skin cancer), and we completed a personal baseline interview that elicited comprehensive health information including data on breast cancer risk factors and NSAID use. All of the cases were adjudicated by WHI physicians using pathology reports. Our analysis was based on 1392 confirmed cases of breast cancer. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated with adjustment for age and other breast cancer risk factors. Regular NSAID use (two or more tablets/week) for 5-9 years produced a 21% reduction in the incidence of breast cancer (RR, 0.79; 95% CI, 0.60-1.04); regular NSAID use for 10 or more years produced a 28% reduction (RR, 0.72; CI, 0.56-0.91), and there was a statistically significant inverse linear trend of breast cancer incidence with the duration of NSAID use (P < 0.01). The estimated risk reduction for long-term use of ibuprofen (RR, 0.51; CI, 0.28-0.96) was greater than for aspirin (RR, 0.79; CI, 0.60-1.03). Subgroup analysis by breast cancer risk factors did not result in effect modification. Regular use of acetaminophen (an analgesic agent with little or no anti-inflammatory activity) or low-dose aspirin (<100 mg) was unrelated to the incidence of breast cancer. Our results indicate that the regular use of aspirin, ibuprofen, or other NSAIDs may have a significant chemopreventive effect against the development of breast cancer and underscore the need for clinical trials to confirm this effect.

Age Factors↗
PubMedDate not supplied

Comorbidity among the morbidly obese: a comparative study of 2002 U.S. hospital patient discharges.

BACKGROUND: Increased morbidity is associated with increasing severity of obesity. However, among morbidly obese patients, comorbid prevalence has been reported primarily in the bariatric surgical literature. This study compares demographic characteristics and selected comorbid conditions of morbidly obese patients discharged after surgical obesity procedures and morbidly obese patients discharged after all other hospital procedures. METHODS: The 2002 National Hospital Discharge Survey (a nationally representative sample of hospital discharge records) and the International Classification of Diseases, 9th Revision, Clinical Modification were used to identify and describe all morbidly obese patient discharges (n = 3,473) and to quantify the prevalence of selected obesity-related comorbid conditions. RESULTS: Compared with all other morbidly obese patients, the obesity surgery patients (n = 833) were younger (median, 42 vs 48 years; range, 17 to 67) and more female (82.3% vs. 63.7%), with higher rates of sleep apnea (24.0% vs. 11.8%), osteoarthritis (22.9% vs. 11.8%), and gastroesophageal reflux disease (27.7% vs. 11.7%) (all P < .001). The prevalence of type 2 diabetes mellitus was lower in the obesity surgery patients (16.1% vs. 24.3%; P = .003), whereas the rates of hypertension (45.9% vs. 41.0%; P = .13) and asthma (9.6% vs. 12.0%; P = .26) were similar in the two groups. CONCLUSIONS: Demographic characteristics and comorbid prevalence of morbidly obese patients discharged after obesity surgery are consistent with reports in the bariatric surgical literature. Obesity surgery patients had a higher prevalence of some comorbid conditions. Possible explanations for this include preferential diagnosis, differential diagnostic coding, or increased severity of morbid obesity. Advancing surgical and insurance guidelines for bariatric surgery will require clinical data that accurately describe and quantify the demographic distribution of obesity and the associated burden of disease.

Adolescent↗
PubMedDate not supplied

Chemoprevention of lung cancer by non-steroidal anti-inflammatory drugs among cigarette smokers.

We conducted an epidemiologic case control study of NSAIDs among 489 lung cancer patients and 978 control subjects. The case patients were diagnosed and treated during 1996-1999 at the James Cancer Hospital and Research Institute, Columbus, OH. Each lung cancer diagnosis was verified by examination of the pathology report. Population controls free of disease were obtained from health screening clinics and frequency-matched to the cases at a 2:1 rate. Matching characteristics included age, gender, and pack-years of cigarette smoking. In order to assess the effects of NSAIDs on tobacco carcinogenesis, only heavy smokers were included in the control group. Information on the use of aspirin, ibuprofen, and prescription NSAIDs was obtained by personal interviews. Effects of NSAIDs on lung cancer risk were assessed by estimating odds ratios (relative risks) with 95% confidence intervals and performing trend tests. Daily intake of NSAIDs for at least 2 years prior to interview was associated with a 68% reduction in the relative risk of lung cancer (RR, 0.32; 95% CI, 0.23-0.44; p<0.01). The inverse trend of lung cancer risk with increasing NSAID use was highly significant (p<0.01). Results were similar for men (RR, 0.41) and women (RR, 0.22), and for the individual compounds, aspirin (RR, 0.25) and ibuprofen (RR, 0.39). These results combined with the current molecular evidence suggest that regular NSAID intake may prevent tobacco carcinogenesis through COX-2 blockade.

Adenocarcinoma↗