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ObjectiveFoetuses and neonates of women who use tobacco are exposed to nicotine and tobacco-derived carcinogens. We determined the relationship between urine biomarkers of tobacco toxicant exposure postpartum and in the neonates of Alaska Native (AN) women, comparing smokers and smokeless tobacco (ST) users, including iqmik, a homemade ST product.MethodsAN women, including 36 smokers, 9 commercial ST and 16 iqmik users their neonates participated. Urine from the woman at the time of delivery and her neonate's first urine were analysed for cotinine, the major metabolite of nicotine, and 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol (NNAL), a tobacco-specific carcinogen biomarker.ResultsMaternal urine cotinine and neonatal urine cotinine were strongly correlated in all tobacco use groups (r from 0.83 to 0.9, p

IntroductionThe high prevalence of smoking and smokeless tobacco (ST) use during pregnancy in Alaska Native (AN) women is concerning due to the detrimental effects of these products to the mother and the developing fetus. We sought to correlate maternal cotinine levels with fetal exposure to a tobacco-specific carcinogen to incorporate in a biomarker feedback intervention to motivate tobacco cessation during pregnancy.MethodsDemographic and tobacco use data were collected from a convenience sample of pregnant AN smokers, ST users, and non-users. Maternal and neonatal urine were collected at delivery. Maternal urine cotinine and neonatal urine total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco-specific carcinogen) levels in smokers and ST users were analyzed and their correlations determined by Spearman correlation coefficients.ResultsDuring 2012-2014, we enrolled 64 non-users, 54 smokers, and 30 ST (20 homemade iqmik; 10 commercial ST) users (n = 148). Analyses of paired maternal-infant urine samples obtained for 36 smokers demonstrated a moderate to strong correlation (r = 0.73, P < .001) between maternal cotinine and infant NNAL levels. The correlation was not significant for 25 iqmik users (r = 0.36, P = .17) or 9 commercial ST users (r = 0.60, P = .09). No analysis was conducted for 55 non-users with cotinine and NNAL levels < limits of quantification.ConclusionsThere is a moderate to strong correlation between maternal smoking and fetal exposure to the tobacco-specific carcinogen NNAL.ImplicationsThe correlation between maternal smoking and fetal carcinogen exposure may provide an education tool to help motivate smoking cessation among pregnant AN women. Further investigation is warranted to determine correlations between maternal commercial ST and iqmik use and neonatal NNAL.

ObjectiveA number of candidate gene and genome-wide association studies have identified significant associations between single nucleotide polymorphisms, particularly in FTO and MC4R, and body weight. However, the association between copy number variation and body weight is less understood. Anabolic androgenic steroids, such as testosterone, can regulate body weight. In humans, UDP-glucuronosyltransferase 2B17 (UGT2B17) metabolizes testosterone to a metabolite, which is readily excreted in urine. We investigate the association between genetic and phenotypic variation in UGT2B17 and body weight.Materials and methodsUGT2B17 deletion was genotyped and in-vivo UGT2B17 enzymatic activity (as measured by the 3-hydroxycotinine glucuronide to free 3-hydroxycotinine ratio) was measured in 400 Alaska Native individuals and 540 African Americans.ResultsIn Alaska Native people, UGT2B17 deletion was strongly associated with lower BMI in male individuals (P

Background and aimsGene variants in CHRNA5-A3-B4, which encode for the α5, α3 and β4 nicotinic receptor subunits, are associated with altered smoking behaviors in European Americans. Little is known about CHRNA5-A3-B4 and its association with smoking behaviors and weight in Alaska Native people, which is a population with high prevalence but low levels of tobacco consumption, extensive smokeless tobacco use and high rates of obesity. We investigated CHRNA5-A3-B4 haplotype structure and its association with nicotine intake and obesity in Alaska Native people.Design, setting and participantsA cross-sectional study of 400 Alaska Native individuals, including 290 tobacco users.MeasurementsCHRNA5-A3-B4 genotype, body weight and tobacco consumption biomarkers such as plasma cotinine and urinary total nicotine equivalents (TNE).FindingsAlaska Native people have a distinct CHRNA5-A3-B4 haplotype structure compared with European/African Americans. In 290 Alaska Native tobacco users the 'G' allele of rs578776, which tagged a 30 kb haplotype in CHRNA5-A3-B4, was prevalent (16%) and associated significantly with nicotine intake (20% higher plasma cotinine, P < 0.001, 16% higher TNE, P = 0.076), while rs16969968 was not associated with nicotine intake. Rs578776 acted in combination with CYP2A6, the main nicotine-metabolizing enzyme, to increase nicotine intake by 1.8-fold compared with the low-risk group (P < 0.001). Furthermore, rs2869950, a single nucleotide polymorphism 5' to CHRNB4, was associated significantly with increased body mass index (P < 0.01) in the tobacco users even after controlling for differences in nicotine intake (P < 0.01).ConclusionsGenetic variants in CHRNA5-A3-B4 alter nicotine intake and body mass index in a population of Alaska Native people, who have a distinct haplotype structure, smoking behaviors and prevalence of obesity.

BackgroundCotinine, a nicotine metabolite, is a biomarker of tobacco, nicotine, and carcinogen exposure. However, a given cotinine level may not represent the same tobacco exposure; for example, African-Americans have higher cotinine levels than Caucasians after controlling for exposure.MethodsCotinine levels are determined by the amount of cotinine formation and the rate of cotinine removal, which are both mediated by the enzyme CYP2A6. Because CYP2A6 activity differs by sex (estrogen induces CYP2A6) and genotype, their effect on cotinine formation and removal was measured in nonsmoking Caucasians (Study 1, n = 181) infused with labeled nicotine and cotinine. The findings were then extended to ad libitum smokers (Study 2, n = 163).ResultsStudy 1: Reduced CYP2A6 activity altered cotinine formation less than cotinine removal resulting in ratios of formation to removal of 1.31 and 1.12 in CYP2A6 reduced and normal metabolizers (P = 0.01), or 1.39 and 1.12 in males and females (P = 0.001), suggesting an overestimation of tobacco exposure in slower metabolizers. Study 2: Cotinine again overestimated tobacco and carcinogen exposure by 25% or more in CYP2A6 reduced metabolizers (≈2-fold between some genotypes) and in males.ConclusionsIn people with slower relative to faster CYP2A6 activity, cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure.ImpactCotinine levels may be misleading when comparing those with differing CYP2A6 genotypes within a race, between races with differing frequencies of CYP2A6 gene variants (i.e., African-Americans have higher frequencies of reduced function variants contributing to their higher cotinine levels), or between the sexes.

IntroductionWe examined the characteristics, attitudes, beliefs, and exposure to tobacco products in a cohort of rural dwelling Alaska Native (AN) people.MethodsWe conducted a study of 400 of AN adult tobacco users and nonusers living in Southwestern Alaska. Questionnaires covered variables such as demographics, tobacco-use history, current tobacco use and dependence scales, general health status, attitudes and beliefs about tobacco, and quitting history.ResultsThe study population smoked 7.8 cigarettes per day compared with 16.8 on average for the U.S. population: a significant proportion of the population engaged in dual use of cigarettes and smokeless tobacco products. Over one third (40.9%), first tried tobacco at age 11 or younger. The mean measures of tobacco addiction (e.g., Fagerstrom Test for Nicotine Dependence, Severson Scale of Smokeless Tobacco Dependence) scores were lower compared with other U.S. populations.ConclusionsVery high tobacco-use prevalence, dual product use, and early tobacco use are observed in Southwestern AN people. Unexpectedly these did not appear to be correlated with heavier individual tobacco use or higher levels of addiction in this population.

Nicotine, the psychoactive ingredient in tobacco, is metabolically inactivated by CYP2A6 to cotinine. CYP2A6 also activates procarcinogenic tobacco-specific nitrosamines (TSNA). Genetic variation in CYP2A6 is known to alter smoking quantity and lung cancer risk in heavy smokers. Our objective was to investigate how CYP2A6 activity influences tobacco consumption and procarcinogen levels in light smokers and smokeless tobacco users. Cigarette smokers (n = 141), commercial smokeless tobacco users (n = 73) and iqmik users (n = 20) were recruited in a cross-sectional study of Alaska Native people. The participants' CYP2A6 activity was measured by both endophenotype and genotype, and their tobacco and procarcinogen exposure biomarker levels were also measured. Smokers, smokeless tobacco users and iqmik users with lower CYP2A6 activity had lower urinary total nicotine equivalents (TNE) and (methylnitrosamino)-1-(3)pyridyl-1-butanol (NNAL) levels (a biomarker of TSNA exposure). Levels of N-nitrosonornicotine (NNN), a TSNA metabolically bioactivated by CYP2A6, were higher in smokers with lower CYP2A6 activities. Light smokers and smokeless tobacco users with lower CYP2A6 activity reduce their tobacco consumption in ways (e.g. inhaling less deeply) that are not reflected by self-report indicators. Tobacco users with lower CYP2A6 activity are exposed to lower procarcinogen levels (lower NNAL levels) and have lower procarcinogen bioactivation (as indicated by the higher urinary NNN levels suggesting reduced clearance), which is consistent with a lower risk of developing smoking-related cancers. This study demonstrates the importance of CYP2A6 in the regulation of tobacco consumption behaviors, procarcinogen exposure and metabolism in both light smokers and smokeless tobacco users.

ObjectivesAlaska Native (AN) people have a high prevalence of tobacco use and associated morbidity and mortality when compared with the general USA population. Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, have not been characterized in AN and may contribute toward the increased risk.MethodsAN people (n=400) residing in the Bristol Bay region of South Western Alaska were recruited for a cross-sectional study on tobacco use. They were genotyped for CYP2A6*1X2A, *1X2B, *1B, *2, *4, *7, *8, *9, *10, *12, *17, *35 and CYP2B6*4, *6, *9 and provided plasma and urine samples for the measurement of nicotine and metabolites.ResultsCYP2A6 and CYP2B6 variant frequencies among the AN Yupik people (n=361) were significantly different from those in other ethnicities. Nicotine metabolism [as measured by the plasma and urinary ratio of metabolites trans-3'-hydroxycotinine to cotinine (3HC/COT)] was significantly associated with CYP2A6 (P

Tobacco cessation interventions developed for Alaska Native adolescents do not exist. This study employed focus group methodology to explore preferences for tobacco cessation interventions and barriers to participation among 49 Alaska Natives (61% female) with a mean age of 14.6 (SD = 1.6) who resided in western Alaska. Using content analysis, themes from the 12 focus groups were found to be consistent across village, gender, and age groups. Program location or site (e.g., away from the village, hunting, fishing), a group-based format, and inclusion of medication and personal stories were reported to be important attributes of cessation programs. Motivators to quit tobacco were the perceived adverse health effects of tobacco, improved self-image and appearance, and the potential to be a future role model as a non-tobacco user for family and friends. Parents were perceived as potentially supportive to the adolescent in quitting tobacco. The findings will be used to develop tobacco cessation programs for Alaska Native youth. (Contains 1 table.)

The article discusses how the activity of the CYP2A6 enzyme, genetics, race and sex affect the ability of the nicotine metabolite called cotinine to predict tobacco, nicotine and carcinogen exposure. Topics covered include the highlights of two studies conducted to characterize the pharmacokinetics of nicotine and cotinine and to examine the relationship between plasma cotinine, nicotine intake and carcinogen exposure, the method used in CYP2A6 genotyping, and how CYP2A6 activity was measured.

Objectives. Tobacco use is the leading cause of preventable death in the United States and contributes to increased incidence, morbidity and mortality from cancer, heart disease, stroke, complications of pregnancy and respiratory illness. Tobacco use rates are highest among American Indians and Alaska Natives. This study examined the prevalence and correlates of tobacco use among youth residing in rural western Alaska. Study design. Data were analysed from the 2003 Youth Risk Behavior Survey (YRBS) administered to a regional sample of adolescents attending school in western Alaska. Methods. Data were analysed from 260 middle school (52% female, 87% Alaska Native) and 258 high school (48% female, 93% Alaska Native) students. Results. Among middle school students, 39% reported current use of ST, 24% reported cigarette smoking and 50% reported current use of any tobacco product. On multivariate analysis, independent correlates of current use of any tobacco were Alaska Native ethnicity (p=0.002) and ever use of marijuana (p<0.001). Among high school students, 38% reported current ST use, 43% reported cigarette smoking and 60% reported current use of any tobacco product. Independent correlates of current use of any tobacco were increasing age (p=0.007), ever use of marijuana (p<0.001), current use of marijuana (p=0.005) and reporting a suicide attempt within the past 12 months (p=0.003). No significant gender differences on tobacco use emerged for middle or high school students. Conclusions. This study documents the high tobacco use rates among youth residing in western Alaska, with over half of the adolescents reporting tobacco use. Developing interventions to promote tobacco use prevention and cessation is an essential step towards reducing tobacco-related health disparities in this rural population. Expanded efforts are needed to address tobacco use among youth residing in this region of Alaska. [ABSTRACT FROM AUTHOR]

Tobacco cessation interventions developed and evaluated for Alaska Native women do not exist. As part of routine clinical care provided at a prenatal visit, a brief tobacco educational intervention for Alaska Native pregnant women (N=100; mean ± SD age = 25.9±6.2 years; mean 6.3± 2.6 months gestation) was piloted at the Y-K Delta Regional Hospital in Bethel, Alaska. This retrospective study reports on the evaluation of this clinical program. The intervention was consistent with the clinical practice guidelines (i.e., 5 A's - ask, advise, assess, assist, arrange), with an average duration of 20.2 ± 6.8 minutes. The self-reported tobacco abstinence rate following the intervention was 11% at the last prenatal visit and 12% at delivery. Delivering a tobacco cessation intervention at a prenatal visit is feasible, but there is a need to identify more effective interventions for Alaska Native pregnant women. [ABSTRACT FROM AUTHOR]

Objective: To determine tobacco use rates during pregnancy among Alaska Natives residing on the Yukon-Kuskokwim (Y-K) Delta of western Alaska. Alaska Natives residing in this region use Iqmik, a unique form of smokeless tobacco (ST)., Study Design: Retrospective cohort study. The medical records of the most recent consecutive 100 Alaska Native women delivering within the Y-K Health Corporation system in 2001 were abstracted for information on tobacco use during this pregnancy and basic demographics., Results: Of the 100 women, 24 did not use tobacco, 55 used ST only, 18 smoked cigarettes only, and 3 used both ST and smoked cigarettes during this pregnancy. Of the 58 who used ST, 22 used Iqmik only, 32 used commercial ST only, and 4 used both. The frequency of ST use increased significantly with age (p=0.007; OR=1.65 per 5-year increase in age, 95% CI 1.15 to 2.36), while the frequency of cigarette smoking tended to decrease with age (p=0.254; OR=0.79 per 5-year increase in age, 95% CI 0.53 to 1.18)., Conclusion: A high proportion of Alaska Native women use tobacco during pregnancy. The rate of ST use (58%) among pregnant Alaska Native women is markedly higher than the prevalence of ST use (0.5%) among women in the general U.S. population.