Discussion:The low enrollment rate suggests that the program was not feasible or acceptable. Alternative approaches are needed to improve the reach and efficacy of cessation interventions for Alaska Native women. IntroductionTobacco use during pregnancy is a major public health problem in the United States. Estimates of smoking prevalence during pregnancy among U.S. women range from 11% to 22% (Goodwin, Keyes, & Simuro, 2007;L. T. Martin, McNamara, et al., 2008). Among U.S. women who gave birth in 2005, the smoking rates during pregnancy were American Indian and Alaska Native (AI/ AN) women (18%), non-Hispanic White (14%), non-Hispanic Black (9%), Hispanic (3%), and Asian women (2%; Substance Abuse and Mental Services Administration [SAMHSA], 2007). Smoking during pregnancy is the leading preventable cause of low infant birth weight and is associated with other maternal and infant adverse perinatal events (Cnattingius, 2004). Less than 1% of U.S. women report smokeless tobacco (ST) use during pregnancy (SAMHSA, 2007). A number of studies report potential adverse health risks of ST use during pregnancy for both the mother and infant including increased risk for preterm birth, stillbirth, and low birth weight (England et al., 2003;Gupta & Subramoney, 2006;Steyn, de Wet, Saloojee, Nel, & Yach, 2006). AbstractBackground: Among Alaska Native women residing in the Yukon-Kuskokwim (Y-K) Delta region of Western Alaska, about 79% smoke cigarettes or use smokeless tobacco during pregnancy. Treatment methods developed and evaluated among Alaska Native pregnant tobacco users do not exist. This pilot study used a randomized two-group design to assess the feasibility and acceptability of a targeted cessation intervention for Alaska Native pregnant women. Methods:Recruitment occurred over an 8-month period. Enrolled participants were randomly assigned to the control group (n = 18; brief face-to-face counseling at the first visit and written materials) or to the intervention group (n = 17) consisting of faceto-face counseling at the first visit, four telephone calls, a video highlighting personal stories, and a cessation guide. Interviewbased assessments were conducted at baseline and follow-up during pregnancy (≥60 days postrandomization). Feasibility was determined by the recruitment and retention rates. Results:The participation rate was very low with only 12% of eligible women (35/293) enrolled. Among enrolled participants, the study retention rates were high in both the intervention (71%) and control (94%) groups. The biochemically confirmed abstinence rates at follow-up were 0% and 6% for the intervention and control groups, respectively.

Background Cotinine, 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. Methods Cotinine levels are determined by the amount of cotinine formation and the rate of cotinine removal which are both mediated by the enzyme CYP2A6. Since CYP2A6 activity differs by sex (estrogen induces CYP2A6) and genotype, their effect on cotinine formation and removal were measured in non-smoking Caucasians (Study 1, n=181) infused with labeled nicotine and cotinine. The findings were then extended to ad libitum smokers (Study 2, n=163). Results Study 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% in CYP2A6 reduced metabolizers (≈2 fold between some genotypes) and in males. Conclusions In people with slower, relative to faster, CYP2A6 activity cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure. Impact Cotinine 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.

Objectives Alaska Native people (AN) have a high prevalence of tobacco use and associated morbidity and mortality when compared to the general U.S. population. Variation in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, has not been characterized in AN and may contribute to the increased risk. Methods AN 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 measurement of nicotine and metabolites. Results CYP2A6 and CYP2B6 variant frequencies among the AN Yupik people (n=361) were significantly different from 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< 0.001) but not CYP2B6 genotype (P = 0.95) when controlling for known covariates. Of note, plasma 3HC/COT ratios were high in the entire Yupik people, and among the Yupik CYP2A6 wild-type participants they were substantially higher than previously characterized racial/ethnic groups (P < 0.001 vs. Caucasians and African Americans). Conclusions Yupik AN people have a unique CYP2A6 genetic profile which associated strongly with in vivo nicotine metabolism. More rapid CYP2A6-mediated nicotine and nitrosamine metabolism in the Yupik people may modulate tobacco-related disease risk.

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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.

Mothers who use Iqmik and their neonates have higher cotinine concentrations compared to mothers who use cigarettes and/or other forms of tobacco. Neurobehavioral signs occur in neonates born to women who use Iqmik but also in neonates born to mothers who use other forms of tobacco during pregnancy.

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.

Introduction: We examined the characteristics, attitudes, beliefs, and exposure to tobacco products in a cohort of rural dwelling Alaska Native (AN) people.