Association of estrogen receptor α gene PvuII and XbaI polymorphisms with non-small cell lung cancer.

Single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER)-α have been found to be associated with various diseases at significantly different frequencies. However, whether any relationship exists between ER-α polymorphisms and lung cancer remains to be determined. In this study, 84 non-smoking, female, non-small cell lung cancer patients with various stages of disease and 234 cancer-free reference controls were enrolled to examine the association of ER-α polymorphisms in lung cancer. Two restriction SNP sites, PvuII and XbaI, in the first intron of the ER-α gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the PvuII-XbaI haplotypes and genotypes in a Taiwanese population were revealed for the first time. Although the genotypic frequencies of two polymorphic sites of ER- α were in linkage disequilibrium for the lung cancer group (χ(2)=50.013, d.f.=4) and reference controls (χ(2)=60.797, d.f.=4); and 7 and 8 combined genotypes were present, respectively, the distribution and the major genotypes are different in the two groups (p<0.0001). The p-values for PvuII and XbaI genotypes were significantly different between the lung cancer and reference controls. The PP genotype presence was found to be significantly lower in the lung cancer group (P=0.005), whereas presence of the xx genotype was significantly higher (P=0.042). These findings suggested that the PP genotype had a lower risk of lung cancer; whereas the xx genotype had a higher risk. In comparison with other studies conducted in various populations, it is of note that the pX haplotype frequency of this study was higher than that of other studies, whereas the px haplotype was lower. Moreover, the Xx genotypic frequency of XbaI polymorphisms in the ER-α gene of the reference control group was found to be extremely high, whereas the xx genotypic frequency was extremely low. In conclusion, PvuII-XbaI polymorphisms of the ER-α gene were found to be associated with the risk, but not cancer severity, of non-small cell lung cancer in a Taiwanese population.