Body Mass Index, Cigarette Smoking, and Alcohol Consumption and Cancers of the Oral Cavity, Pharynx, and Larynx: Modeling Odds Ratios in Pooled Case-Control Data

study-specific results, their findings should be interpreted with caution

How much do smoking and alcohol consumption explain socioeconomic inequalities in head and neck cancer risk?

Background A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. Methods We conducted a case-control study in Sao Paulo, Brazil (1998-2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. Results Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. Conclusions Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.

An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies

Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (a parts per thousand yen25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.

Alcohol consumption in homicide victims in the city of Sao Paulo

Aims To assess the association between alcohol use and victimization by homicide in individuals autopsied at the Institute of Legal Medicine in Sao Paulo, Brazil. Design Cross-sectional study. Setting Excessive consumption of alcohol is a serious public health issue and a major factor in triggering violent situations, which suggests a strong association between alcohol ingestion and becoming a victim of homicide. Participants Data from 2042 victims of homicides in 2005 were obtained from medical examiner reports. Measurements The victim`s gender, age, ethnicity and blood alcohol concentration (BAC) were collected. The method of death and homicide circumstances, as well as the date, time and place of death were also studied. Findings Alcohol was detected in blood samples of 43% of the victims, and mean BAC levels were 1.55 +/- 0.86 g/l. The prevalence of positive BAC levels was higher among men (44.1%) than women (26.6%), P < 0.01. Firearms caused most of the deaths (78.6%), and alcohol consumption was greater among victims of homicide by sharp weapons (P < 0.01). A greater proportion of victims with positive BAC were killed at weekends compared to weekdays (56.4 and 38.5%, respectively; P < 0.01), and the correlation between homicide rates and the average BAC for the central area of the city was positive (r(s) = 0.90; P < 0.01). Conclusions These results highlight alcohol as a contributing factor for homicide victimization in the greatest urban center in South America, supporting public strategies and future research aiming to prevent homicides and violence related to alcohol consumption.

Maternal alcohol consumption may influence cord blood ascorbic acid concentration: findings from a study of Brazilian mothers and their newborns

Studies that have investigated ascorbic acid (AA) concentrations in cord blood have pointed to significant associations with maternal blood AA concentrations. smoking, age, diet, type of delivery, duration of gestation, fetal distress and birth weight. The aim of the present study was to determine the relationship between cord blood AA concentrations in newborns and maternal characteristics. A total of 117 Brazilian healthy parturients were included in this cross-sectional study. The concentrations of AA in blood were determined by the HPLC method. Data concerning socio-economic, demographic, obstetric, nutritional and health characteristics of the parturients, including alcohol consumption and smoking habit, were assessed by a standardised questionnaire. A FFQ was used to investigate the intake of foods rich in vitamin C. Cord blood AA concentration was significantly correlated with per capita income (r 0.26; P=0.005), maternal blood AA concentration (r 0.48; P<0.001) and maternal vitamin C-rich food intake score (r 0.36; P<0.001). The linear regression model including maternal AA concentration, alcohol consumption, smoking, parity, vitamin C-rich food intake score and per capita income explained 31.13% of the variation in cord blood AA concentrations in newborns. We recommend further experimental studies to assess the effects of ethanol on placental AA uptake, and epidemiological cohort studies to evaluate in detail the influence of maternal alcohol consumption on cord blood AA concentrations.

Relation between alcohol consumption and traffic violations and accidents in the region of Ribeirao Preto, Sao Paulo State

In recent years, alcohol consumption has been considered an important public health problem. Ethanol, the alcohol used in beverages, is a drug that affects the central nervous system (CNS) and impairs driving skills and co-ordination, increasing risk of deaths and injuries derived from crashes and road accidents. Consumption of alcoholic beverages is implicated with premature deaths, injuries and damages caused by motor vehicle crashes, which result in high costs to government and society. Considering that alcohol consumption is the main responsible factor for deaths and disabilities in young people, the aim of this work was to evaluate the prevalence of blood alcohol in offenders and/or fatal and non-fatal victims of traffic occurrences in the region of Ribeirao Preto, Sao Paulo State, from 2005 to 2007. The results revealed that in 2134 cases investigated, blood alcohol positivity was generally found in young adults, 25-45 years old and male. The study showed the high risk of drinking and driving and the importance in establishing actions of prevention and intervention to promote the reduction in the number of traffic occurrences related to consumption of alcoholic beverages. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Alcohol and drug consumption among sexual offenders

Purpose: To evaluate the role of alcohol and drug consumption between sexual offenders against boys and girls. Method: It was an observational, retrospective and cross-sectional study carried out by the Ambulatory for the treatment of sexual disorders of ABC Medical College, Santo Andre, Sao Paulo, Brazil (ABSex). The sample comprised 104 convicts, over 18 years old, sentenced only for sexual crimes against children (below 11 years old). Alcohol and drug consumption, sexual abuse history, sexual impulsivity, and risk of recidivism were evaluated. Results: The sexual offenders against boys showed higher alcohol consumption problems than sexual offenders against girls (chi(2) = 19.76, 1 d.f., p < 0.01). The severity of alcohol consumption was also significantly higher in the sexual offenders against non-related boys than in the sexual offenders against non-related girls (p = 0.037, ANOVA). After adjustment for other variables, such as monthly income before the penalty and alcohol consumption at the moment of the crime, the alcohol consumption severity in sexual offenders against boys was significantly higher than in sexual offenders against girls (OR = 1.05, CI 1.01-1.08, p < 0.01). Conclusions: Alcohol use or abuse is associated with the perpetration of sexual aggression. The role of alcohol consumption seems to be greater in sexual offenders against boys than in girls and this can contribute to criminal recidivism. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Associations between glutathione peroxidase-1 Pro198Leu polymorphism, selenium status, and DNA damage levels in obese women after consumption of Brazil nuts

Objective: Alterations in selenium (Se) status may result in suboptimal amounts of selenoproteins, which have been associated with increased oxidative stress levels. The Pro198Leu polymorphism at the glutathione peroxidase-1 (GPx1) gene is supposed to be functional. The response of Se status, GPx activity, and levels of DNA damage to a Se supplementation trial between the genotypes related to that polymorphism was investigated. Methods: A randomized trial was conducted with 37 morbidly obese women. Participants consumed one Brazil nut, which provided approximately 290 mu g of Se a day, for 8 wk. Blood Se concentrations, erythrocyte GPx activity, and DNA damage levels were measured at baseline and at 8 wk. The results were compared by genotypes. Results: The genotype frequencies were 0.487, 0.378, and 0.135 for Pro/Pro (the wild-type genotype), Pro/Leu, and Leu/Leu, respectively. At baseline, 100% of the subjects were Se deficient, and after the supplementation, there was an improvement in plasma Se (P < 0.001 for Pro/Pro and Pro/Leu, P < 0.05 for Leu/Leu), erythrocyte Se (P = 0.00 for Pro/Pro and Pro/Leu, P < 0.05 for Leu/Leu), and GPx activity (P = 0.00 for Pro/Pro, P < 0.00001 for Pro/Leu, P < 0.001 for Leu/Leu). In addition, the Pro/Pro group showed a decrease in DNA damage after Brazil nut consumption compared with baseline (P < 0.005), and those levels were higher in Leu/Leu subjects compared with those with the wild-type genotype (P < 0.05). Conclusion: Consumption of one unit of Brazil nuts daily effectively increases Se status and increases GPx activity in obese women, regardless of GPx1 Pro198Leu polymorphism. However, the evaluated biomarkers showed distinct results in response to the supplementation when the polymorphism was considered. (c) 2011 Elsevier Inc. All rights reserved.

Gender-specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase

Background and purpose: Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats. Experimental approach: Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively. Key results: In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L-NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats. Conclusions and implications: Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS.

Alcohol-related traffic accidents with fatal outcomes in the city of Sao Paulo

Aims: The aims of the present study were to characterize fatal traffic accident victims in a major urban center in Brazil and their association with alcohol consumption. Methods: Cross-sectional study of 907 fatal traffic accident victims in Sao Paulo, in 2005. Results: Adult males between the ages of 25 and 54 represented the majority of cases with positive blood alcohol concentrations (BAC). Overall, males had a higher proportional BAC and mean BAC than females. Pedestrians, particularly those with no detectable BAC, were typically older than other victims. Most accidents (total and BAC-positive) happened on weekends between midnight and 6 a.m. Considering all victims, 39.4% were positive (BAC over 0.1 g/l). When only drivers (automobile, motorcycle and bicycle) were evaluated. 42.3% had BAC over the legal limit (0.6 g/l). Conclusions: Alcohol is associated with nearly half of all traffic accident deaths in the city of Sao Paulo. especially for days and times associated with parties and bars (weekends between 12 a.m. and 6 a.m.). (C) 2010 Elsevier Ltd. All rights reserved.

Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male mice

Low to moderate doses of alcohol consumption induce heightened aggressive behavior in some, but not all individuals. Individual vulnerability for this nonadaptive behavior may be determined by an interaction of genetic and environmental factors with the sensitivity of alcohol`s effects on brain and behavior. We used a previously established protocol for alcohol oral self-administration and characterized alcohol-heightened aggressive (AHA) mice as compared with alcohol non-heightened (ANA) counterparts. A week later, we quantified mRNA steady state levels of several candidate genes in the serotonin [5-hydroxytryptamine (5-HT)] system in different brain areas. We report a regionally selective and significant reduction of all 5-HT receptor subtype transcripts, except for 5-HT(3), in the prefrontal cortex of AHA mice. Comparable gene expression profile was previously observed in aggressive mice induced by social isolation or by an anabolic androgenic steroid. Additional change in the 5-HT(1B) receptor transcripts was seen in the amygdala and hypothalamus of AHA mice. In both these areas, 5-HT(1B) mRNA was elevated when compared with ANA mice. In the hypothalamus, AHA mice also showed increased transcripts for 5-HT(2A) receptor. In the midbrain, 5-HT synthetic enzyme, 5-HT transporter and 5-HT receptors mRNA levels were similar between groups. Our results emphasize a role for postsynaptic over presynaptic 5-HT receptors in mice which showed escalated aggression after the consumption of a moderate dose of alcohol. This gene expression profile of 5-HT neurotransmission components in the brain of mice may suggest a vulnerability trait for alcohol-heightened aggression.

Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats

Chronic ethanol Consumption and hypertension are related. In the current study we investigated whether changes in reactivity of the mesenteric arterial bed could account for the increased blood pressure associated with chronic ethanol intake. Changes in reactivity to phenylephrine and acetylcholine were investigated in the perfused mesenteric bed from rats treated with ethanol for 2 or 6 weeks and their age-matched controls. Mild hypertension was observed in chronically ethanol-treated rats. Treatment of rats for 6 weeks induced an increase in the contractile response of endothelium-intact mesenteric bed to phenylephrine, but not denuded rat mesenteric bed. The phenylephrine-induced increase in perfusion pressure was not altered after 2 weeks` treatment with ethanol. Moreover, acetylcholine-induced endothelium-dependent relaxation was reduced by ethanol treatment for 6 weeks, but not 2 weeks. Pre-treatment with indometacin, a cyclooxygenase inhibitor, reduced the maximum effect induced by phenylephrine (E-max) in endothelium-intact mesenteric bed from both control and ethanol-treated rats. No differences in the E-max values for phenylephrine were observed between groups in the presence of indometacin. L-NNA, a nitric oxide (NO) synthase (NOS) inhibitor, increased the E-max for phenylephrine in endothelium-intact mesenteric bed from control rats but not from ethanol-treated rats. Levels of endothelial NOS (eNOS) mRNA were not altered by chronic ethanol consumption. However, chronic ethanol intake strongly reduced eNOS protein levels in the mesenteric bed. This study shows that chronic ethanol consumption increases blood pressure and alters the reactivity of the mesenteric bed. Moreover, the increased vascular response to phenylephrine observed in the mesenteric bed is maintained by two mechanisms: an increased release of endothelial-derived vasoconstrictor prostanoids and a reduced modulatory action of endothelial NO, which seems to be associated with reduced post-transcriptional expression of eNOS.

Long-Term Ethanol Consumption Promotes Hepatic Tumorigenesis but Impairs Normal Hepatocyte Proliferation in Rats

Chronic and excessive alcohol consumption has been related to an increased risk of several cancers, including that of the liver; however, studies in animal models have yet to conclusively determine whether ethanol acts as a tumor promoter in hepatic tumorigenesis. We examined whether prolonged alcohol consumption could act as a hepatic tumor promoter after initiation by diethylnitrosamine (DEN) in a rat model. Male Sprague-Dawley rats were injected with 20 mg DEN/kg body weight 1 wk before introduction of either an ethanol liquid diet or an isoenergic control liquid diet. Hepatic pathological lesions, hepatocyte proliferation, apoptosis, PPAR alpha and PPAR gamma, and plasma insulin-like growth factor 1 IGF-1) levels were assessed after 6 and 10 mo. Mean body and liver weights, plasma IGF-1 concentration, hepatic expressions of proliferating cellular nuclear antigen and Ki-67, and cyclin D1 in ethanol-fed rats were all significantly lower after 10 mo of treatment compared with control rats. In addition, levels of hepatic PPAR gamma protein, not PPAR alpha, were significantly higher in the ethanol-fed rats after prolonged treatment. Although ethanol feeding also resulted in significantly fewer altered hepatic foci, hepatocellular adenoma was detected in ethanol-fed rats at 10 mo, but not in control rats given the same dose of DEN. Together, these results indicate that chronic, excessive ethanol consumption impairs normal hepatocyte proliferation, which is associated with reduced IGF-1 levels, but promotes hepatic carcinogenesis. J. Nutr. 141: 1049-1055, 2011.

Ethanol consumption and pineal melatonin daily profile in rats

It is well known that melatonin participates in the regulation of many important physiological functions such as sleep-wakefulness cycle, motor coordination and neural plasticity, and cognition. However, as there are contradictory results regarding the melatonin production diurnal profile under alcohol consumption, the aim of this paper was to study the phenomenology and mechanisms of the putative modifications on the daily profile of melatonin production in rats submitted to chronic alcohol intake. The present results show that rats receiving 10% ethanol in drinking water for 35 days display an altered daily profile of melatonin production, with a phase delay and a reduction in the nocturnal peak. This can be partially explained by a loss of the daily rhythm and the 25% reduction in tryptophan hydroxylase activity and, mainly, by a phase delay in arylalkylamine N-acetyltransferase gene expression and a 70% reduction in its peak activity. Upstream in the melatonin synthesis pathway, the results showed that noradrenergic signaling is impaired as well, with a decrease in beta 1 and alpha 1 adrenergic receptors` mRNA contents and in vitro sustained loss of noradrenergic-stimulated melatonin production by glands from alcohol-treated rats. Together, these results confirm the alterations in the daily melatonin profile of alcoholic rats and suggest the possible mechanisms for the observed melatonin synthesis modification.