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Журнал научных статей «Здоровье и образование в XXI веке» №3, 2012 том 14
THE PLA POLYMORHISM OF INTEGRIN BETA3 AND CANCER RISK
Myandina G.I., Kovalev A.V., Tarasenko E.V., EikhenvaldL.A .
Peoples Friendship University of Russia, Moscow, Russia
Key words: integrin receptor, PLA polymorphism, cancer risk, tumor progression.
Motivation and Aim: Platelets and their fibrinogen receptors may be central to haematogenous cancer spread, in addition to various adhesive proteins on both platelets and tumor cells on themselves. The glycoprotein alpha(IIb)beta3a (GPIIb/nia) is the main fibrinogen receptor on platelets. The PLA polymorphism of the beta3 subunit modulates the function of alpha(IIb)beta3a integrin. We examined whether this polymorphism influences the cancer risk and progression.
Methods and Algorithms: Using participants (n = 150) from the Moscow population, we assessed the risk of prostate cancer (PC) and bladder cancer (BC) in individuals with the PLA polymorphism (heterozygote and homozygote) relative to those without the polymorphism (non-carriers). A study group of 90 patients with prostate cancer, 30 patients with bladder cancer and 30 age-matched controls healthy volunteers were measured for genotype using DNA extracted from freshly drawn blood. Integrin PLA polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Relative risks (RRs) of cancer and 95% confidence intervals (CIs) were calculated by Cox proportional hazards regression analysis. Statistical tests were two-sided.
Results: in Moscow population 76% are non-carriers (PLA1/PLA1), 22% are heterozygote (PLA1/PLA2), and 2% are homozygote (PLA2/PLA2) [1]. Among the patients with cancer 57.8% were non-carries, 37.8% were heterozygote and 4.4% were homozygote. The frequency of PLA2 carries was significantly higher in patients with cancer, comparing to population frequency (p<0.02). Concerning the metastases group for bladder cancer the frequency of PLA2 polymorphism carries was higher (41.7%) than in non-invasive group (23.3%). For the PLA1/PLA2 carries the frequency of local prostate cancer is 2.8 times higher and of metastases prostate cancer is 2,4 times higher than that for non-carries patients (PLA1/PL1).
Conclusion: We conclude that the integrin PLA polymorphism does not modify the cancer risk but it may influence the metastasis spread and the malignant potential of bladder and prostate cancer. The tumor progression for the patients with PLA2 in genotype has a greater rate of local invasion and metastases. Our findings are compatible with laboratory observations that the integrin Leu33Pro polymorphism is associated with increased reactivity and aggregability of platelets in vitro [2] and with increased cell cycle progression or proliferation of tumor cells through extracellular signal-related kinase [3], which has an impact on metastasis and malignant potential of tumor bladder cancer.
Availability: the determination of PLA polymorphism seems to be a new prognostic factor for bladder and prostate cancer and is useful and convenient for high risk patients screening and treatment.
References:
1. Мяндина Г.И. и др.(2006) Аллель PLA2 гена гликопротеина GP3a как фактор генетической
предрасположенности к онкологическим заболеваниям мочеполовой системы, Вестник РУДН, №2 (34): 14 - 18.
2. A.D. Michelson et al.(2000) Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists,
Circulation, 101:1013-1018.
3. J. Downward (2003) Targeting RAS signaling pathways in cancer therapy, Nat. Rev. Cancer, 3:11-22
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Материалы XIVмеждународного конгресса «Здоровье и образование в XXI веке» РУДН, Москва, 2012
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