Association of a genetic variant of CYP19A1 with multicentric development of lung adenocarcinomas.

Background: The detection rate of multiple lung adenocarcinomas, which display multiple ground glass opacity nodules in the peripheral lung, is increasing because of advances in high resolution computed tomography. The genetic backgrounds of multiple nodules and the mechanisms that underlie their multicentric development are unknown. In this study, we examined single nucleotide polymorphisms (SNPs) of the cytochrome P450 19A1 gene to determine if they are associated with multiple adenocarcinomas risk.

Methods: Fifty-one cases of multiple adenocarcinomas with lepidic growth, 62 cases of a single adenocarcinoma with lepidic growth, and 126 control cases were analyzed. Three SNPs were analyzed by using a 5' nuclease assay with TaqMan minor-groove-binder probe. The expression level of CYP19A1 in the noncancerous lung was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR).

Results: A minor allele of SNP rs3764221, which is located in the CYP19A1 gene, was significantly associated with multiple adenocarcinomas risk (adjusted odds ratio = 3.06; P = 0.006). Other polymorphisms of CYP19A1 were not significantly associated with the risk of multiple adenocarcinomas. A minor allele of SNP rs3764221 was also associated with a higher level of CYP19A1 messenger RNA expression (P = 0.03).

Conclusions: SNP rs3764221 contributes to the development of multicentric adenocarcinomas in the peripheral lung by causing higher levels of CYP19A1 expression.