Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression.

In adenocarcinoma cases only (test for heterogeneity by histology: p heterog = 0.066), the minor allele of CYP1B1 rs10175368 was significantly protective for lung cancer (OR = 0.8, 95%CI = 0.69–0.93, p trend = 0.003) and a similar protective effect was nominally significant (i.e. p-value≤0.05) for the CYP1B1 rs9341266 polymorphism.

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However, we identified a borderline significant protective association (freq = 0.03, p-value = 0.059) with a three-locus haplotype with a C, G, and T in locus 1, 2 and 8, respectively, which was also contained in the 8 SNP haplotype.

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We found that the 8 polymorphisms in the 15q24 chromosomal region had a significant down-regulating effect on mRNA expression for CYP1A1 gene among the 14 never smokers (δ = −1.51, p-value = 0.007) and showed a trend for up-regulation among the 15 current smokers (δ = 4.95, p-value = 0.078).

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For the 8 SNPs in EPHX1 gene, we observed an overall trend for decreasing expression (δ = −1.20, p-value = 0.096), which was nominally significant among the 15 former smokers (δ = −2.56, p-value = 0.049).

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The smoking-genotype interaction was highly significant (p interact = 0.006).

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