XRCC1 polymorphism and lung cancer risk in relation to tobacco smoking

DNA repair plays a critical role in protecting the genome of the cell from carcinogens or ionising radiation. Reduced DNA-repair capacity can increase susceptibility to occupational-induced cancer. Three coding polymorphisms at codons 194, 280, and 399 in X-ray cross complementing group 1 (XRCC1) DNA-repair gene have been identified, and it is possible that these polymorphisms may affect DNA- repair capacity and thus modulate cancer susceptibility. In the current German study, we investigated the role of XRCC1-polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes, especially in relation to tobacco smoking. Three polymorphisms; XRCC1 Arg194Trp, XRCC1 Arg280His and XRCC1 Arg399Gln, were determined by real-time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients who carried at least one mutant variant allele of XRCC1 Arg194Trp (OR=1.03; 95%-CI: 0.66-1.61), XRCC1 Arg280His (OR=0.95; 95%-CI: 0.57-1.60), or XRCC1 Arg399Gln (OR=0.99 CI: 0.73-1.34), did not show any elevated risks. When analysed by histology, no individual subtype of lung cancer was significantly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption. Stratified analysis between tobacco smoking and variant genotypes revealed increasing risks for heavy smokers (>60 pack-years), with the presence of at least one copy of the XRCC1 Arg194Trp variant allele (OR=79.29; 95%-CI: 8.53-737.04) and the XRCC1 Arg399Gln (OR=61.87; 95%-CI: 15.65-244.67). By analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study, the XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln-polymorphisms, had no relevant modifying effect on lung cancer risk and cumulative smoking dose.     

Pulmonary hazards of smoking marijuana as compared with tobacco

To compare the pulmonary hazards of smoking marijuana and tobacco, we quantified the relative burden to the lung of insoluble particulates (tar) and carbon monoxide from the smoke of similar quantities of marijuana and tobacco. The 15 subjects, all men, had smoked both marijuana and tobacco habitually for at least five years. We measured each subject's blood carboxyhemoglobin level before and after smoking and the amount of tar inhaled and deposited in the respiratory tract from the smoke of single filter-tipped tobacco cigarettes (900 to 1200 mg) and marijuana cigarettes (741 to 985 mg) containing 0.004 percent or 1.24 percent delta 9-tetrahydrocanabinol. As compared with smoking tobacco, smoking marijuana was associated with a nearly fivefold greater increment in the blood carboxyhemoglobin level, an approximately threefold increase in the amount of tar inhaled, and retention in the respiratory tract of one third more inhaled tar (P less than 0.001). Significant differences were also noted in the dynamics of smoking marijuana and tobacco, among them an approximately two-thirds larger puff volume, a one-third greater depth of inhalation, and a fourfold longer breath-holding time with marijuana than with tobacco (P less than 0.01). Smoking dynamics and the delivery of tar during marijuana smoking were only slightly influenced by the percentage of tetrahydrocanabinol. We conclude that smoking marijuana, regardless of tetrahydrocannabinol content, results in a substantially greater respiratory burden of carbon monoxide and tar than smoking a similar quantity of tobacco.     

Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer

The role and significance of microsatellite instability (MSI) in gastric carcinogenesis remain unknown. This study determined the chronology of MSI in gastric carcinogenesis by examining intestinal metaplasia (IM) from patients with and without gastric cancer. DNA was obtained from gastric specimens of 75 patients with gastric IM (30 cancer, 26 peptic ulcer, and 19 chronic gastritis patients) and was amplified with a set of eight microsatellite markers. Eight (26. 7%) tumors and seven (9.3%) IM samples (three from cancer-free patients) displayed high-level MSI (three or more loci altered). Low-level MSI (one or two loci altered) was detected in 50% of the tumors, in 40% of IM samples coexisting with cancer, and in 38% of IM tissues of cancer-free individuals. Among the 30 cancer patients, microsatellites were more frequently altered in IM coexisting with tumors that showed MSI (P = 0.003). In addition, patients with low-level MSI in the tumor tissues were more likely to have active Helicobacter pylori infection than those with stable tumors (P = 0.02). In conclusion, this study indicates that MSI occurs not only in gastric IM of patients with gastric carcinoma, but also in IM of cancer-free individuals. These data suggest that the progressive accumulation of MSI in areas of IM may contribute to gastric cancer development, representing an important molecular event in the multistep gastric carcinogenesis cascade.     

Serum peptidome profiling in patients with gastric cancer

To identify discriminating protein patterns in serum samples between gastric cancer patients (early and advanced stages) and healthy controls. We used magnetic bead-based separation followed by matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) to identify patients with gastric cancer. In total, serum samples from 62 gastric cancer patients (32 in the training set and 30 in the test set; 19 of which had early-stage tumors and 43 of which had advanced-stage tumors) and 64 healthy controls (32 in the training set and 32 in the test set) were analyzed. The mass spectra, analyzed using ClinProTools software, distinguished between cancer patients and healthy individuals based on three different algorithm models. In the training set, patients with gastric cancer could be identified with a mean sensitivity of 94.7% and a mean specificity of 99%. Similar results were obtained with the test set, showing 79.3% sensitivity and 86.5% specificity. Our study demonstrates the high sensitivity and specificity of screening serum protein patterns using MALDI-TOF MS for the identification of patients with gastric cancer.     

Alterations of humoral immunity in patients with gastric cancer

For better understanding of the alterations of humoral immunity in gastric cancer patients, IgG, IgA, IgM, complement C3, C4, CH50, natural antibody (isohemagglutinin-IgM class), ESR, CRP, albumin and globulin were quantitated in sera taken preoperatively from 81 patients with gastric cancer and from 29 control patients with hernia. The results from patients with gastric cancer were grouped according to pTNM staging (including stage I + II, III, and IV). Serum globulin and IgG levels in all stages of cancer patients were significantly lower than that of the controls (p less than 0.05). The CRP and ESR levels in stage III and IV cancer patients were significantly higher (p less than 0.05). There was no difference between cancer and hernia patient groups in IgA, IgM, isohemagglutinin-IgM class, C3, C4, CH50, albumin, WBC and total lymphocyte counts. In conclusion, the significant changes in humoral immunity in patients with gastric cancer include: (1) decrease in serum IgG and globulin levels, and (2) increased levels of acute phase reactants (ESR, CRP). These results imply that patients with gastric cancer have lower acquired humoral immunity and have acute phase reactions.     

The epidemiological characteristics of tobacco smoking

The author analyses the pattern of the occurrence and development of tobacco addiction among the city population of Samara. Analysis of the epidemiological features of tobacco smoking in Samara shows that its prevalence is quite high among both men and women, especially young ones. The prevalence of smoking depends on the level of education and family status; the proportion of smokers is the smallest among married people with higher education. These facts evidence the necessity of active anti-smoking preventive measures that would integrate efforts of the medical community and would be directed towards different social population groups.     

Secretion of interleukin-1\ and tumor necrosis factor by blood mononuclears in patients with breast cancer: Effects of body weight (Composition), age,and tobacco smoking

Examinations of patients with breast cancer and mammary fibroadenomatosis suggest a relationship between the secretion of interleukin-1β and tumor necrosis factor by blood mononuclears, on the one hand, and patients' age, body weight, and body fat, on the other. A modifying (discoordinating) role of tobacco smoking in the realization of this process is noted. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 91–93, January, 1996 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences     

Prevalence and correlates of tobacco use among Russian cancer patients: Implications for the development of smoking cessation interventions at a cancer center in Russia

This study examined the rate of smoking among 399 cancer patients in Russia and assessed correlates of tobacco use and readiness to quit smoking. The results indicated that (a) 41.6% of patients were smokers; and (b) smokers were likely to be male, have lung or colorectal cancer, exhibit low levels of knowledge concerning the negative effects of smoking, report a low level of advantages to quitting smoking and a high level of disadvantages to quitting smoking, show low perceived risk for the adverse effects of smoking, and exhibit high fatalistic beliefs. Though certain findings converge well with data collected from U.S. samples of cancer patients, these results can guide the development of smoking interventions that address the specific needs of Russian cancer patients. In sum, this study fills a critical gap in knowledge concerning the epidemic of tobacco use in Russia and broadens research regarding tobacco use by cancer patients from the United States to the Russian Federation. Support for this study was provided by National Institutes of Health grant CA95678 (R. Schnoll) and by a U.S. federal appropriation to the American-Russian Cancer Alliance.     

Surgical outcome of synchronous second primary cancer in patients with gastric cancer

PURPOSE: In order to improve the likelihood of curative and safe gastric surgery, this study investigated the clinical features and surgical outcomes of gastric cancer with a synchronous cancer. PATIENTS AND METHODS: The clinicopathological data of 10,090 gastric cancer patients at Samsung Medical Center from September 1994 to December 2006 were retrospectively analyzed. Of them, 90 patients with gastric cancer and a synchronous second primary cancer underwent simultaneous surgery for gastric cancer and second primary cancer. The clinicopathological characteristics of the patients, surgical outcome, and prognosis were examined. RESULTS: The most common synchronous second primary cancer was colorectal cancer (37 patients), followed by hepatocellular carcinoma (13 patients), renal cell carcinoma (11 patients), and pancreatic carcinoma (5 patients). The incidence of a second primary cancer in the gastric cancer patients was higher than the incidence in the general population. Stage I gastric cancer patients had more synchronous cancers than stage II patients (59 vs. 31). Postoperative complications were encountered in 7 patients. Four patients underwent reoperation. Two patients died from hepatic failure and leakage of esophagojejunal anastomosis. The 5-year survival rate of stage I and II gastric cancer was 61% and 39%, respectively. CONCLUSION: Since gastric cancer patients with a synchronous second primary cancer are not rare, the possibility of synchronous cancers in gastric cancer patients should be considered. The prognosis of early stage gastric cancer patients with a synchronous second primary cancer was influenced more by the presence of the second primary cancer than by the gastric cancer itself.     

Duration judgements in patients with schizophrenia

BACKGROUND: The ability to encode time cues underlies many cognitive processes. In the light of schizophrenic patients' compromised cognitive abilities in a variety of domains, it is noteworthy that there are numerous reports of these patients displaying impaired timing abilities. However, the timing intervals that patients have been evaluated on in prior studies vary considerably in magnitude (e.g. 1 s, 1 min, 1 h etc.). METHOD: In order to obviate differences in abilities in chronometric counting and place minimal demands on cognitive processing, we chose tasks that involve making judgements about brief durations of time (< 1 s). RESULTS: On a temporal generalization task, patients were less accurate than controls at recognizing a standard duration. The performance of patients was also significantly different from controls on a temporal bisection task, in which participants categorized durations as short or long. Although time estimation may be closely intertwined with working memory, patients' working memory as measured by the digit span task did not correlate significantly with their performance on the duration judgement tasks. Moreover, lowered intelligence scores could not completely account for the findings. CONCLUSIONS: We take these results to suggest that patients with schizophrenia are less accurate at estimating brief time periods. These deficits may reflect dysfunction of biopsychological timing processes.