Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals

Lips, E. H. et al. (2010) Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. International Journal of Epidemiology, 39(2), pp. 563-577. (doi:10.1093/ije/dyp288)

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Abstract

<b>Background</b> Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens.<p></p> <b>Methods</b> We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies.<p></p> <b>Results</b> Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P < 0.001). The variant was associated with heavy smoking (>20 CPD) [odds ratio (OR) = 1.13, 95% confidence interval (CI) 0.96–1.34, P = 0.13 for heterozygotes and 1.81, 95% CI 1.39–2.35 for homozygotes, P < 0.0001]. The strong association between the variant and LC risk (OR = 1.30, 95% CI 1.23–1.38, P = 1 × 10<sup>–18</sup>), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR = 1.27, 95% CI 1.19–1.35, P = 5 × 10<sup>–13</sup>). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P = 0.02). The association was also noted in UADT cancers (OR = 1.08, 95% CI 1.01–1.15, P = 0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour.<p></p> <b>Conclusions</b> This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.<p></p>

Item Type:Articles
Keywords:AGE ASSOCIATION CANCER CIGARETTE-SMOKING ENGLAND FAGERSTROM TOLERANCE QUESTIONNAIRE GENE HEALTH HEAVY SMOKING INDIVIDUALS INTERVAL Lung cancer LUNG-CANCER NICOTINE DEPENDENCE POLYMORPHISM RECEPTOR SUBUNIT GENES RISK SMOKING smoking quantity SUSCEPTIBILITY LOCUS UADT cancer WHOLE-GENOME ASSOCIATION WIDE ASSOCIATION
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Conway, Professor David
Authors: Lips, E. H., Gaborieau, V., McKay, J. D., Chabrier, A., Hung, R. J., Boffetta, P., Hashibe, M., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., Field, J. K., Liloglou, T., Xinarianos, G., McLaughlin, J., Liu, G., Skorpen, F., Elvestad, M. B., Hveem, K., Vatten, L., Benhamou, S., Lagiou, P., Holcatova, I., Merletti, F., Kjaerheim, K., Agudo, A., Castellsague, X., Macfarlane, T. V., Barzan, L., Canova, C., Lowry, R., Conway, D. I., Znaor, A., Healy, C., Curado, M. P., Koifman, S., Eluf-Neto, J., Matos, E., Menezes, A., Fernandez, L., Metspalu, A., Heath, S., Lathrop, M., and Brennan, P.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:International Journal of Epidemiology
Publisher:Oxford University Press
ISSN:0300-5771
ISSN (Online):1464-3685
Published Online:23 September 2009
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