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CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations.

ABSTRACT: We investigated genetic variation in CYP2A6 in relation to lung cancer risk among African American smokers, a high-risk population. Previously, we found that CYP2A6, a nicotine/nitrosamine metabolism gene, was associated with lung cancer risk in European Americans, but smoking habits, lung cancer risk and CYP2A6 gene variants differ significantly between European and African ancestry populations. Herein, African American ever-smokers, drawn from two independent lung cancer case-control studies, were genotyped for reduced activity CYP2A6 alleles and grouped by predicted metabolic activity. Lung cancer risk in the Southern Community Cohort Study (n = 494) was lower among CYP2A6 reduced versus normal metabolizers, as estimated by multivariate conditional logistic regression [odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.26-0.73] and by unconditional logistic regression (OR = 0.62; 95% CI = 0.41-0.94). The association was replicated in an independent study from MD Anderson Cancer Center (n = 407) (OR = 0.64; 95% CI = 0.42-0.98), and pooling the studies yielded an OR of 0.64 (95% CI = 0.48-0.86). Exploratory analyses revealed a significant interaction between CYP2A6 genotype and sex on the risk for lung cancer (Southern Community Cohort Study: P = 0.04; MD Anderson: P = 0.03; Pooled studies: P = 0.002) with a CYP2A6 effect in men only. These findings support a contribution of genetic variation in CYP2A6 to lung cancer risk among African American smokers, particularly men, whereby CYP2A6 genotypes associated with reduced metabolic activity confer a lower risk of developing lung cancer.

SUBMITTER: Wassenaar CA

PROVIDER: S-EPMC4291053 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations.

Wassenaar Catherine A CA Ye Yuanqing Y Cai Qiuyin Q Aldrich Melinda C MC Knight Joanne J Spitz Margaret R MR Wu Xifeng X Blot William J WJ Tyndale Rachel F RF

Carcinogenesis 20141121 1

We investigated genetic variation in CYP2A6 in relation to lung cancer risk among African American smokers, a high-risk population. Previously, we found that CYP2A6, a nicotine/nitrosamine metabolism gene, was associated with lung cancer risk in European Americans, but smoking habits, lung cancer risk and CYP2A6 gene variants differ significantly between European and African ancestry populations. Herein, African American ever-smokers, drawn from two independent lung cancer case-control studies, ...[more]

PMID: 25416559

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Project description:Anhedonia-diminished interest and pleasure in response to rewards-may be a symptom of tobacco withdrawal that is understudied in priority populations. This experiment investigated the magnitude and correlates of various dimensions of anhedonia during tobacco withdrawal among African-American (AA) smokers-a population subject to health disparities. AA smokers (N = 607; ≥ 10 cigarettes/day, 37.8% female, M[SD] age = 50.0[10.6] years) completed self-report measures assessing expected pleasure from (i.e., consummatory anhedonia) and desire to engage in (i.e., anticipatory anhedonia) various types of hypothetically experienced rewards at counterbalanced 16-hr tobacco deprived and nondeprived lab visits. Other tobacco withdrawal symptom measures (e.g., craving, negative affect, hunger) were also assessed. Tobacco deprivation most robustly increased scores on a composite measure of consummatory anhedonia directed toward various reward domains (i.e., hobbies, sensory experiences, social activities; d = .32, p < .001). Deprivation modestly increased consummatory and anticipatory anhedonia directed toward sexual rewards (ds = .09-.12, ps < .02), did not significantly change anhedonia toward food rewards, and decreased anhedonia directed toward psychoactive drug rewards (i.e., increased desire for and pleasure from drugs; ds = -.21 to -.19, ps < .001). Deprivation-induced changes in anhedonia were modestly correlated with other withdrawal symptoms (average |r|s = .04-.23) and were amplified among participants with higher nicotine dependence and lower positive affect-related traits (|β|s = .10-.12, ps < .01). Some dimensions of anhedonia may be genuine expressions of acute tobacco withdrawal in AA smokers. Applying multi-dimensional anhedonia conceptualizations might advance basic knowledge and treatment of tobacco use disorder, improve smoking cessation outcomes, and address tobacco-related health disparities facing AA smokers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Project description:ImportanceThe United States Preventive Services Task Force (USPSTF) recommends low-dose computed tomography screening for lung cancer. However, USPSTF screening guidelines were derived from a study population including only 4% African American smokers, and racial differences in smoking patterns were not considered.ObjectiveTo evaluate the diagnostic accuracy of USPSTF lung cancer screening eligibility criteria in a predominantly African American and low-income cohort.Design, setting, and participantsThe Southern Community Cohort Study prospectively enrolled adults visiting community health centers across 12 southern US states from March 25, 2002, through September 24, 2009, and followed up for cancer incidence through December 31, 2014. Participants included African American and white current and former smokers aged 40 through 79 years. Statistical analysis was performed from May 11, 2016, to December 6, 2018.ExposuresSelf-reported race, age, and smoking history. Cumulative exposure smoking histories encompassed most recent follow-up questionnaires.Main outcomes and measuresIncident lung cancer cases assessed for eligibility for lung cancer screening using USPSTF criteria.ResultsAmong 48 364 ever smokers, 32 463 (67%) were African American and 15 901 (33%) were white, with 1269 incident lung cancers identified. Among all 48 364 Southern Community Cohort Study participants, 5654 of 32 463 African American smokers (17%) were eligible for USPSTF screening compared with 4992 of 15 901 white smokers (31%) (P < .001). Among persons diagnosed with lung cancer, a significantly lower percentage of African American smokers (255 of 791; 32%) was eligible for screening compared with white smokers (270 of 478; 56%) (P < .001). The lower percentage of eligible lung cancer cases in African American smokers was primarily associated with fewer smoking pack-years among African American vs white smokers (median pack-years: 25.8 [interquartile range, 16.9-42.0] vs 48.0 [interquartile range, 30.2-70.5]; P < .001). Racial disparity was observed in the sensitivity and specificity of USPSTF guidelines between African American and white smokers for all ages. Lowering the smoking pack-year eligibility criteria to a minimum 20-pack-year history was associated with an increased percentage of screening eligibility of African American smokers and with equitable performance of sensitivity and specificity compared with white smokers across all ages (for a 55-year-old current African American smoker, sensitivity increased from 32.2% to 49.0% vs 56.5% for a 55-year-old white current smoker; specificity decreased from 83.0% to 71.6% vs 69.4%; P < .001).Conclusions and relevanceCurrent USPSTF lung cancer screening guidelines may be too conservative for African American smokers. The findings suggest that race-specific adjustment of pack-year criteria in lung cancer screening guidelines would result in more equitable screening for African American smokers at high risk for lung cancer.

Dataset Information

CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations.

Publications

CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations.

Similar Datasets

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