Polymorphisms of dopamine receptor/transporter genes and risk of non-small cell lung cancer.
BACKGROUND
The dopaminergic pathway may be of interest in assessing risk of non-small cell lung cancer (NSCLC). Dopamine receptors are expressed in alveolar epithelial cells and human lung tumours, and dopamine inhibits both cell proliferation in vitro and growth of lung tumour xenografts in nude mice. Moreover, dopamine selectively inhibits the vascular permeability and angiogenic activity of vascular endothelial growth factor (VPF/VEGF). The bioavailability of dopamine is regulated by dopamine receptors D2 (DRD2), D4 (DRD4) and dopamine transporter 1 (DAT1/SLC6A3) genes.


METHODS
We have analysed 10 single nucleotide polymorphisms in DRD2, DRD4 and DAT1/SLC6A3 genes in relation to lung cancer risk in a case-control study of smoking subjects. The study subjects were 413 healthy individuals from general population and 335 NSCLC cases. Both cases and controls were Caucasians of Norwegian origin.


RESULTS
We demonstrate that DRD2 polymorphisms -141Cdel, 3208G>T, TaqIB; DRD4 -521C>T and DAT1/SLC6A3 -1476T>G are associated with a two- to five-fold increased NSCLC risk. The variant alleles of DRD2 1412A>G and 960C>G had protective effects.


CONCLUSIONS
The dopamine receptor/transport gene polymorphisms are associated with the risk of NSCLC among smokers. The data show that the polymorphisms resulting in lower dopamine bioavailability were associated with increased risk of NSCLC.
Campa
Daniele
D
International Agency for Research on Cancer, Lyon, France.
Zienolddiny
Shanbeh
S
Lind
Helge
H
Ryberg
David
D
Skaug
Vidar
V
Canzian
Federico
F
Haugen
Aage
A
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011954:Receptors, Dopamine / Q000235:genetics*; D012306:Risk; D012907:Smoking
D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine