Role of polymorphisms in codons 143 and 160 of the O6-alkylguanine DNA alkyltransferase gene in lung cancer risk

O6-Alkylguanine DNA alkyltransferase (AGT) plays an important role in the repair of alkylating agent-induced DNA damage and protection from the carcinogenic effects of environmental agents. To examine the importance of the AGT codon 143 and codon 160 polymorphisms in risk for lung cancer and to assess the prevalence of these polymorphisms in different racial groups, we performed genotype analysis of lung cancer patients and matched controls. The prevalence of the AGT143Val allele in controls was 0.07 in Caucasians and 0.03 in African Americans. The AGT143Val allele was not detected in an unmatched Asian control cohort. The prevalence of the AGT160Arg variant allele was 0.01 in Caucasians, 0.02 in African Americans, and 0.03 in Asians. A marginally significant association was observed between the AGT codon 143 (isoleucine/valine) genotype and risk for lung cancer (odds ratio = 2.1; 95% confidence interval = 1.01– 4.7). The prevalence of the AGT160Arg variant allele was similar in lung cancer cases versus matched controls. These results suggest that the AGT codon 143 polymorphism may play an important role in risk for lung cancer

Time to First Cigarette after Waking Predicts Cotinine Levels

There is wide variability in cotinine levels per cigarette smoked. We hypothesized that in addition to smoking frequency, other behavioral measures of nicotine dependence, such as the time to first cigarette after waking, are associated with cotinine levels. To test this hypothesis, we measured plasma and urinary cotinine in a community-based study of 252 black and white daily cigarette smokers. Among one pack per day smokers, plasma cotinine levels varied from 16 to 1,180 ng/mL, a 74-fold difference. Two nicotine dependence phenotypes were discerned by time after waking. Subjects in the “low” dependent phenotype smoked > 30 minutes after waking and nearly all smoked ≤20 cigarettes per day. Cotinine levels increased linearly with cigarette consumption in this group. Subjects in the “high” dependent phenotype smoked ≤30 minutes after waking but had a wide range in the frequency of daily cigarettes (6-70). Compared with the low dependent phenotype, there were relatively small differences in cotinine by cigarette frequency with evidence of a plateau effect in heavy smokers (∼30). After adjusting for cigarette frequency, the levels of cotinine by time to first cigarette were as follows: ≤5 minutes, 437 [95% confidence limits (CL), 380-494]; 6 to 30 minutes, 352 (95% CL, 291-413), 31 to 60 minutes, 229 (95% CL, 140-317), and > 60 minutes, 215 (95% CL, 110-321). Similar findings were observed for urinary cotinine. These findings suggest that the time to first cigarette is a strong predictor of nicotine uptake and should be considered in the design of smoking interventions. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3415–20

Risk of Lung Carcinoma Among Users of Nonsteroidal Antiinflammatory Drugs

BACKGROUND; Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the development of lung tumors in experimental animals. To the authors' knowledge there are little data regarding whether regular use of NSAIDs reduces the risk of developing lung carcinoma in humans. METHOD; The association between lung carcinoma risk and regular use of NSAIDs, including aspirin, was evaluated in a hospital-based case–control study of 1038 patients and 1002 controls. RESULTS; The relative risk estimate of lung carcinoma associated with using NSAIDs 3 times a week or more for 1 or more years demonstrated an odds ratio (OR) of 0.68 (95% confidence interval [95% CI], 0.53–0.89). Results were similar when separated by lung histologic type. The association varied by smoking status. The OR was1.28 (95% CI, 0.73–2.25) in never-smokers and 0.60 (95% CI 0.45–0.80) in ever-smokers. The smoking-specific risk estimates for aspirin were similar to those for all NSAIDs. CONCLUSIONS; The results of the current study suggest a possible chemoprotective benefit with the use of NSAIDs among individuals who are former or current smokers

Menthol Smoking in relation to Time to First Cigarette and Cotinine: Results from a Community-based Study

Smokers who have their first cigarette shortly after waking, an indicator of nicotine dependence, have substantially higher cotinine levels. There is controversy regarding the role of menthol in nicotine dependence. We hypothesized that menthol smokers have a shorter time to first cigarette (TTFC), and tested whether any statistical association actually reflects increased dependence by measuring nicotine uptake (e.g. cotinine) in the same group of smokers. A cross-sectional community-based study was conducted that included 495 black and white daily cigarette smokers. Results showed a trend between menthol smoking and a shorter TTFC (P less than 0.04 in blacks). Menthol was not an independent predictor of cotinine or an effect modifier with TTFC on cotinine levels in blacks and whites. These results show that while menthol in tobacco is associated with an indicator of nicotine dependence in blacks, menthol was not associated with biological uptake of nicotine in black and white smokers

The Nicotine Dependence Phenotype, Time to First Cigarette, and Larynx Cancer Risk

Purpose Cigarette smoking is the major cause of laryngeal cancer. The time to first cigarette after waking in the morning is a behavior associated with several dimensions of nicotine dependence including the dose of smoke uptake. We hypothesized that a short TTFC increases the risk of laryngeal cancer. Methods The analysis was based on data from a hospital-based case–control study of laryngeal cancer. The current analysis included only subjects who were ever cigarette smokers, including 570 cases and 343 controls (832 whites and 81 blacks). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression adjusting for smoking history and other potential confounders. Incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 1975 to 2006 were analyzed for trends in laryngeal cancer. Results There was a dose–response relationship between TTFC and supraglottic cancer. Compared to subjects who smoked more than 60 min after waking, the adjusted odds ratio was 1.51 (95% CI, 0.63–3.61) for 30–60 min and 3.13 (95% CI, 1.56–6.30) for 0–30 min. No association was observed between TTFC and cancer of the glottis. In blacks, the TTFC was not associated with the risk of laryngeal cancer. Trends in SEER rates were similar for cancer of the glottis and supraglottis, indicating that the site-specific differences were not affected by unknown confounders. Conclusion A nicotine dependence behavior that is associated with cigarette smoke uptake increases the risk of cancer of the supraglottis larynx, but not glottis larynx

The First International Mini-Symposium on Methionine Restriction and Lifespan

It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met) ingestion by rats extends lifespan (Orentreich et al., 1993). Since then, several studies have replicated the effects of dietary methionine restricted (MR) in delaying age-related diseases (Richie et al., 1994; Miller et al., 2005; Ables et al., 2012; Sanchez-Roman and Barja, 2013). We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY, September 2013. The goals were (1) to gather researchers with an interest in MR and lifespan, (2) to exchange knowledge, (3) to generate ideas for future investigations, and (4) to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH), and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones, and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g., the naked mole rat, Brandt's bat, and Drosophila, in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies (Figure 3)

Use of Oral Cholera Vaccines in an Outbreak in Vietnam: A Case Control Study

Simple measures such as adequate sanitation and clean water stops the spread of cholera; however, in areas where these are not available, cholera spreads quickly and may lead to death in a few hours if treatment is not initiated immediately. The use of life-saving rehydration therapy is the mainstay in cholera control, however, the rapidity of the disease and the limited access to appropriate healthcare units in far-flung areas together result in an unacceptable number of deaths. The WHO has recommended the use of oral cholera vaccines as a preventive measure against cholera outbreaks since 2001, but this was recently updated so that vaccine use may also be considered once a cholera outbreak has begun. The findings from this study suggest that reactive use of killed oral cholera vaccines provides protection against the disease and may be a potential tool in times of outbreaks. Further studies must be conducted to confirm these findings

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion