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Lookup NU author(s): Dr Ray Lowry
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Methods 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. Results 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 x 10(-18)), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR = 1.27, 95% CI 1.19-1.35, P = 5 x 10(-13)). 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. Conclusions 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.
Author(s): Lips EH, Gaborieau V, McKay JD, Chabrier A, Hung RJ, Boffetta P, Hashibe M, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Field JK, Liloglou T, Xinarianos G, McLaughlin J, Liu G, Skorpen F, Elvestad MB, Hveem K, Vatten L, Benhamou S, Lagiou P, Holcatova I, Merletti F, Kjaerheim K, Agudo A, Castellsague X, Macfarlane TV, Barzan L, Canova C, Lowry R, Conway DI, Znaor A, Healy C, Curado MP, Koifman S, Eluf-Neto J, Matos E, Menezes A, Fernandez L, Metspalu A, Heath S, Lathrop M, Brennan P, EPIC Study
Publication type: Article
Publication status: Published
Journal: International Journal of Epidemiology
Year: 2010
Volume: 39
Issue: 2
Pages: 563-577
Print publication date: 01/04/2010
ISSN (print): 0300-5771
ISSN (electronic): 1464-3685
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/ije/dyp288
DOI: 10.1093/ije/dyp288
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