Genetic variation in platelet integrin alphabeta (GPIIb/IIIa) and the metastatic potential of renal cell carcinoma.
OBJECTIVE
To explore whether genetic polymorphisms in platelet receptors known to be associated with platelet activity have any association with haematogenous metastases in renal cell carcinoma (RCC), as platelets and their fibrinogen receptors may be central to haematogenous cancer spread, in addition to various adhesive proteins on both platelets and tumour cells on themselves.


METHODS
The glycoprotein alpha(IIb)beta3 (GPIIb/IIIa) is the main fibrinogen receptor on platelets, with GPIb-IX-V and GPIa/IIa being the von Willebrand Factor and collagen receptors, respectively. In a cross-sectional survey of 128 men treated for RCC (55 with disseminated disease and 73 with a local disease), they were genotyped using DNA extracted from freshly drawn blood, and central clinical data were recorded.


RESULTS
The frequency of possessing the GPIIIaPl(A2) allele among patients with metastatic RCC was 43.6%, and with local disease was 24.7% (P = 0.024). The frequencies of the different alleles of the GIB-IX-V, C3550T and GPIa/IIa C807T polymorphisms did not differ between the groups. In a stepwise logistic regression (metastatic vs local RCC) the Pl(A2) allele remained a significant risk factor, with an odds ratio of 2.7 (95% confidence interval, 1.1-6.5; P = 0.02).


CONCLUSIONS
The prothrombotic Pl(A2) allele of platelet fibrinogen receptor GPIIb/IIIa increased the risk of metastases in RCC in men.
Kallio
Jukka P
JP
Department of Urology, Tampere University Hosital, Tampere, Finland. jp.kallio@elisanet.fi
Mikkelsson
Jussi
J
Tammela
Teuvo L J
TL
Karhunen
Pekka J
PJ
Kellokumpu-Lehtinen
Pirkko
P
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000556:secondary*; D003430:Cross-Sectional Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
D019039:Platelet Glycoprotein GPIIb-IIIa Complex