risks to tobacco smoking: Haplotype 1-2-1, or G-C-A, had a frequency of 0.363 in the regular smokers and that of 0.307 in the non-smokers (P = 0.0373), and haplotype 1-2-2, or G-C-G, was observed only in the regular smokers (frequency = 0.013, P = 0.0023). For ND, only the minor haplotype 1-2-2 was significant (the frequency in the High-ND group was 0.022, that in the Low-ND group was 0.002, P = 0.010). By comparing the patterns of association, it was clear that haplotype 1-2-2 associated with both SI and ND, while haplotype 1-2-1 was associated only with SI. The most abundant haplotype, 1-1-1 for combination 5-6-7 was significantly underrepresented in the regular smokers (P = 0.0167). Combination 1-3-5-6-7 produced similar results as that of combination 5-6-7. The P values for the global and individual haplotype tests were all comparable. These results indicated that the major risk haplotype defined by markers 5–7 extended to marker 1 in exon 1, the non-synonymous Asn40Asp polymorphism. This risk haplotype carried the A (Asn) allele.
