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Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6- alkylguanine-DNA alkyltransferase

Lookup NU author(s): Dr Mauro Santibanez Koref


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The association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O6- alkylguanine-DNA alkyltransferase, which are associated with interindividual differences in activity, have been investigated in 3 hospital-based case-control studies. Genotyping was carried out on 617 subjects of whom 255 had lung cancer. In 2 of the 3 series, there was a significant inverse association between the 178R allele and case status (p < 0.05). In a meta-analysis, the odds ratio (95% CI) associated with the 178R allele relative to the 178K allele was 0.64 (0.45-0.92, p = 0.01) and 0.51 (0.24-1.11, p = 0.09) in fixed effects and random effects models, respectively. In a pooled analysis, after adjustment for sex, age, pack years and series, the OR (95% CI) for a heterozygote was 0.67 (0.45-1.01) and for a 178R homozygote was 0.10 (0.01-0.94); the trend for a decreased risk with the number of R alleles was significant (p = 0.008). This trend was particularly pronounced in heavy smokers (trend test p = 0.003), but not significant in light smokers (p = 0.73). There was no evidence of an association between rs12268840 and lung cancer risk. These results suggest that the R allele may protect against lung cancer, specifically in heavy smokers, an effect that may result from this polymorphism affecting the function of the MGMT protein and/or levels in MGMT activity. © 2007 Wiley-Liss, Inc.

Publication metadata

Author(s): Crosbie PAJ, McGown G, Thorncroft MR, O'Donnell PNS, Barber PV, Lewis SJ, Harrison KL, Agius RM, Santibanez-Koref MF, Margison GP, Povey AC

Publication type: Article

Publication status: Published

Journal: International Journal of Cancer

Year: 2008

Volume: 122

Issue: 4

Pages: 791-795

ISSN (print): 0020-7136

ISSN (electronic): 1097-0215

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/ijc.23059

PubMed id: 17957803


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