Sadik A. Khuder

Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis.

Although cigarette smoking is an established risk factor for lung cancer, the strength of association with different histologic types is not well understood. This meta-analyses of peer-reviewed studies was conducted to assess the effect of cigarette smoking on major histologic types of lung cancer. Studies were identified through MEDLINE and CANCERLIT searches. A total of 48 studies published between 1970 and 1999 were identified. Combined estimates of relative risks (OR) and 95% confidence intervals (CI) were calculated using fixed and random effect models. Separate analyses were conducted by study design and gender. A linear dose-response was fit to studies reporting data on intensity and duration of smoking. All histologic types of lung cancer were significantly associated with cigarette smoking. The association was stronger with squamous cell carcinoma (SQC) and small cell carcinoma (SCLC) than with large cell cancer (LGC) and adenocarcinoma (ADC). The combined OR for heaviest smoking intensity (30+ cigarettes per day) ranged from 4.10 (CI 3.16-5.31) for ADC to 18.3 (CI 9.26-36.4) for SCLC. The combined OR for longest duration of smoking (40+ years) ranged from 3.80 (CI 2.35-6.16) for ADC to 38.6 (CI 11.9-125) for SCLC. In women, the combined OR for SQC and SCLC were higher than those in men. The dose response curve for intensity of smoking was steeper in women. The findings of this study provide additional evidence for a causal relationship between smoking and all histologic types of lung cancer.

Breast cancer and NSAID use: a meta-analysis.

Recent epidemiological studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of several cancers including breast cancer. This meta-analysis examined the studies on NSAID use and breast cancer. The estimators of relative risk and associated variances, which have been adjusted for the greatest number of confounders, were abstracted and included in the meta-analysis. Combined estimators of relative risk (RR) were calculated using either fixed or random effect models. Meta-analyses were performed on 6 cohort studies (number of cases ranged from 14 to 2414) and 8 case–control studies (number of cases ranged from 252 to 5882). The combined estimate of relative risk was 0.82 (95% confidence interval [CI] = 0.75–0.89). The combined estimate for cohort studies was 0.78 (95% CI = 0.62–0.99) and was 0.87 (95% CI = 0.84–0.91) for case–control studies. The findings of this meta-analysis suggest that NSAID use may be associated with a small decrease in the risk of breast cancer. However, the available data are insufficient to estimate the dose–response effect for duration and frequency of use of any particular types of NSAID.

Age at smoking onset and its effect on smoking cessation.

The aim of this study was to examine the relationship between cessation and age at which person starts smoking. Data from a survey of nine neighborhoods in Philadelphia (1985-1987) were analyzed. Interviews were conducted in the home using a structured questionnaire. Participants were from a probability sample (n = 1,700) of males aged 35 years or older. Sixty-six percent of the smokers in this series started smoking before 18 years of age. Smoking cessation rate was 58.1% in Whites and 38.8% in Blacks. Age, race, marital status, education, health condition, amount smoked, and duration of smoking were significant predictors of smoking cessation. Age at initiation of smoking was a significant factor for continuation of smoking. Men who started smoking before 16 years of age had an odds ratio of 2.1 (95% confidence interval: 1.4-3.0) for not quitting smoking compared to those who started at a later age. These findings emphasize the need for prevention program targeted to children below 16 years of age.

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

Background— Preservation of renal function is an important objective of renal artery stent procedures. Although atheroembolization can cause renal dysfunction during renal stent procedures, whether adjunctive use of embolic protection devices or glycoprotein IIb/IIIa inhibitors improves renal function is unknown. Methods and Results— One hundred patients undergoing renal artery stenting at 7 centers were randomly assigned to an open-label embolic protection device, Angioguard, or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor, abciximab, in a 2×2 factorial design. The main effects of treatments and their interaction were assessed on percentage change in Modification in Diet in Renal Disease–derived glomerular filtration rate from baseline to 1 month using centrally analyzed creatinine. Filter devices were analyzed for the presence of platelet-rich thrombus. With stenting alone, stenting and embolic protection, and stenting with abciximab alone, glomerular filtration rate declined (P<0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2×2 design (P<0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0±27% versus −10±20%; P<0.05), embolic protection was not (−1±28% versus −10±20%; P=0.08). An interaction was observed between abciximab and embolic protection (P<0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (P<0.01). Conclusions— Renal artery stenting alone, stenting with embolic protection, and stenting with abciximab were associated with a decline in glomerular filtration rate. An unanticipated interaction between Angioguard and abciximab was seen, with combination therapy better than no treatment or either treatment alone.

ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines

BackgroundAlthough 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.ResultsFollowing validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC, ABCC5/GTF2H2, ERCC2/GTF2H2, XPA/XPC and XRCC1/XPC. All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was (ABCC5/GTF2H2, ERCC2/GTF2H2) with an R2 value of 0.96 (p < 0.001).ConclusionThese results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.

Meta-analyses of multiple myeloma and farming

A series of meta-analyses of peer-reviewed studies of multiple myeloma (MM) and farming were performed, using 32 studies published between 1981 and 1996. Prior to the meta-analyses, all studies were reviewed and evaluated for heterogeneity and publication bias. A random-effects meta-analysis including all of the studies yielded an estimator of relative risk equal to 1.23, with a 95% confidence interval (95% CI) of 1.14, 1.32. The estimator of relative risk obtained from a meta-analysis restricted to female farmers was 1.23 (95% CI = 1.17, 1.29). A third meta-analysis restricted to studies of farmers residing in the central United States resulted in an estimator of relative risk equal to 1.38 (95% CI = 1.27, 1.51). These findings were not influenced by either a publication bias or a specific study design. The consistent significant positive findings suggest that there is an association between MM and farming. Exposures commonly experienced by farmers and that might contribute to the occurrence of MM include infectious microorganisms, solvents and pesticides.

Use of Complementary and Alternative Therapies in HIV-Infected Patients

The use of complementary and alternative medicine (CAM) therapies is widespread in many chronic illnesses, including human immunodeficiency virus (HIV) infection. The objective of this study was to determine the impact of increasingly effective antiretroviral therapy on the use of CAM in an HIV-positive patient population. A written survey was given to 191 HIV-positive outpatients. Participation was voluntary and anonymous. One hundred twenty-eight patients (67%) used CAM at some time to control HIV and 76 (40%) of the patients were currently using CAM. The major forms of CAM used were exercise (43%), lifestyle changes (38%), dietary supplements (37%), counseling (27%), herbal medications (26%), megavitamins (24%), and prayer therapy (24%). One hundred forty-one patients (74%) used a protease inhibitor medication, 28 (15%) used a protease inhibitor sparing regime, and 22 (11%) had no current or prior antiretroviral use. Eighty-two (43%) patients indicated that their doctor knew they used CAM and 56 patients (29%) received their information about CAM from a doctor or other health care professional. Of 128 patients who used CAM, 90 (70%) felt CAM improved their quality of life. Income of

Meta-analyses of prostate cancer and farming

15,000 or more per year and discontinuation of medications by patients for any reason in the past were the best predicators of CAM use for patients in general and also those on protease inhibitor therapy. CD(4) count, educational status, year of HIV diagnosis, and martial status were not effective predictors of CAM use. Use of CAM remains widespread among patients with HIV infection even with the availability of effective, yet noncurative antiretroviral therapy and does not correlate with type of antiretroviral therapy used or clinical status.

Meta-analyses of brain cancer and farming

Articles published in peer-reviewed journals between January 1983 and June 1994 were reviewed for inclusion in a meta-analysis designed to estimate the relative risk of prostate cancer in farmers. Three analyses were performed: (1) an analysis including all articles written during the specified time period that listed an estimate of the relative risk of prostate cancer in farmers: (2) an analysis that included only retrospective studies; and (3) an analysis that included only studies reporting a standardized mortality ratio. Positive associations between prostate cancer and farming were found by the analysis including all studies and the analysis limited to the retrospective studies. No association was found with the analysis that included only studies reporting a standard mortality ratio. The most plausible explanation for the positive association between prostate cancer and farming is exposure to hormonally active agricultural chemicals.

Increased von Willebrand factor in migraine

BACKGROUND A series of meta-analyses of peer-reviewed studies of brain cancer and farming were performed, using 33 studies published between 1981 and 1996. METHODS Before the meta-analyses, all studies were reviewed and evaluated for heterogeneity and publication bias. A random-effect model was used to estimate the combined relative risk. RESULTS A meta-analysis including all the studies yielded an estimator of relative risk equal to 1.30, with a 95% confidence interval (95% CI) of 1.09, 1.56. The estimator of relative risk obtained from a meta-analysis restricted to female farmers was 1.04 (95% CI = 0.84, 1.29). A third meta-analysis restricted to studies of farmers residing in the central United States resulted in an estimator of relative risk equal 1.25 (95% CI = 1.09, 1.44). These findings were not influenced by either a publication bias or a specific study design. CONCLUSION The consistent significant positive findings suggests that there is a weak association between brain cancer and farming. Exposures commonly experienced by farmers including infectious microorganisms and pesticides may contribute to the increased risk of brain cancer.