Jia Y Wan1, Christina Cataby2, Andrew Liem1, Emily Jeffrey1, Trina M Norden-Krichmar1, Deborah Goodman1, Stephanie A Santorico3, Karen L Edwards4. 1. Department of Epidemiology, University of California, Irvine, United States. 2. Department of Population Health and Disease Prevention, University of California, Irvine, United States. 3. Department of Mathematical and Statistical Sciences, University of Colorado, Denver, United States. 4. Department of Epidemiology, University of California, Irvine, United States; Department of Population Health and Disease Prevention, University of California, Irvine, United States. Electronic address: kedward1@uci.edu.
Abstract
BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. RESULTS: After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). CONCLUSIONS: To our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.
BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. RESULTS: After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). CONCLUSIONS: To our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.
Authors: Carolyn M Hutter; Jenny Chang-Claude; Martha L Slattery; Bethann M Pflugeisen; Yi Lin; David Duggan; Hongmei Nan; Mathieu Lemire; Jagadish Rangrej; Jane C Figueiredo; Shuo Jiao; Tabitha A Harrison; Yan Liu; Lin S Chen; Deanna L Stelling; Greg S Warnick; Michael Hoffmeister; Sébastien Küry; Charles S Fuchs; Edward Giovannucci; Aditi Hazra; Peter Kraft; David J Hunter; Steven Gallinger; Brent W Zanke; Hermann Brenner; Bernd Frank; Jing Ma; Cornelia M Ulrich; Emily White; Polly A Newcomb; Charles Kooperberg; Andrea Z LaCroix; Ross L Prentice; Rebecca D Jackson; Robert E Schoen; Stephen J Chanock; Sonja I Berndt; Richard B Hayes; Bette J Caan; John D Potter; Li Hsu; Stéphane Bézieau; Andrew T Chan; Thomas J Hudson; Ulrike Peters Journal: Cancer Res Date: 2012-02-24 Impact factor: 12.701