Meme Kanserinde TP53 (RS1042522) Polimorfizmi

Öz

Amaç: TP53 geni temel olarak DNA tamiri, apoptozis, hücre yaşlanması ve hücre döngüsü kontrolünde görev alan en önemli tümör baskılayıcı genlerden biridir. TP53 rs1042522 (Arg72Pro) polimorfizmi tümör baskılama sırasında P53 protein yapısında değişikliğe neden olan bir polimorfizmdir. Bu verilere dayanarak, bu çalışmanın amacı TP53 rs1042522 polimorfizmi ve meme kanseri riski arasındaki ilişkiyi araştırmaktır.

Yöntem: TP53 rs1042522 polimorfizmi için 508 meme kanserli kadın hastadan ve 367 sağlıklı kadından alınan periferik kanlardan DNA izole edilerek PCR-RFLP yöntemi ile genotipleme yapıldı. İstatistiksel analiz, %95 güven aralığında χ2 testi ile yapıldı ve Hardy-Weinberg eşitliği (HWE) test edilen hastalar ve kontrol popülasyonu için doğrulandı.

Bulgular: Genotip frekansları sırasıyla hasta ve kontrollerde GG alleli için %48.6, %46.3, GC alleli için %40.7, %44.7ve CC alleli için de %10.6, %9.0 şeklindedir. Vaka ve control genotipleri arasında istatistiksel olarak fark olmadığı bulundu (χ2=1.591, P= 0.451). Allel frekansı G alleli için vakalarda %69.0 ve kontrollerde %69.0, C alleli için vakalarda %31.0 kontrollerde %31.0 şeklinde ortaya çıktı. Sonuçlar istatistiksel olarak anlamsız bulundu (G allel: p=0.424, C allel: p=0.501). TP53 rs1042522 genotip dağılımı kontrol popülasyonu için Hardy-Weinberg eşitliğine göre kararlı bulundu (p>0.05).

Sonuç: Çalışmamızda meme kanseri ile p53 geninde yer alan rs1042522 polimorfizminin tek başına değerlendirildiğinde meme kanseri riski ile ilişkisi olmadığı bulunmuştur. P53’ün karsinogenezdeki rolünden ve özellikle de programlı hücre ölümünden sorumlu çeşitli proteinlerle etkileşime girmesinden dolayı rs1042522 polimorfizmini diğer proteinlerdeki değişimlerle birlikte çalışmak daha anlamlı olabilir. Ayrıca, farklı TP53 polimorfizmleri ile hücre döngüsünde görevli siklin, sikline bağımlı kinazlar ve p21 gibi genlerin ortak etkilerine odaklanılabilinir ya da bu polimorfizmin daha geniş bir hasta popülasyonunda tümörlerin klinikopatolojik özellikleri ile birlikte değerlendirilmesi daha anlamlı sonuçlar verebilir.

Anahtar Kelimeler

• P53 geni,rs1042522,polimorfizm,meme kanseri

TP53 (RS1042522) Polymorphism In Breast Cancer

Öz

Objectives: TP53 gene is one of the most important tumour suppressor gene that mainly plays a role in DNA repair, cell apoptosis, cell senescence and cell cycle control. TP53 rs1042522 (Arg72Pro) polymorphism is nonsynonymous polymorphism that alters P53 protein capacity during tumour suppression. Based on the data above, the purpose of this study is to investigate association between TP53 rs1042522 polymorphism and breast cancer risk in hospital-based Turkish women population.

Methods: After DNA isolation from peripheral blood of 508 breast cancer patients and 367 healthy women the genotyping for TP53 rs1042522 polymorphism in both groups was done by a PCR-RFLP method. Statistical analysis was done by the χ2 test with 95% confidence intervals and the Hardy-Weinberg equilibrium was confirmed for tested patient and control populations.

Results: Genotype frequencies were 48.6%, 46.3% for GG, 40.7%, 44.7% for GC and 10.6%, 9.0% for CC in breast cancer and controls, respectively. There was not statistical difference between genotypes in cases and controls (χ2=1.591, P= 0.451). Allele frequencies for G allele were 69.0% in cases and 69.0% in controls, for C allele 31.0% in cases and 31.0 % in controls. Also, this results were found to be not statistically significant for G and C alleles (G allele: p=0.424, C allele: p=0.501). The distribution of TP53 rs1042522 genotypes was in agreement with HWE for controls (p>0.05).

Conclusion: There is no statistically significant association between rs1042522 and the risk of breast cancer in studied hospital- based Turkish women population. For further, rs1042522 polymorphism may be associated with other genetic factors due to the interaction of p53 with various proteins that play role in programmed cell death. Also, the combined effect of TP53 polymorphisms and the genes such as cyclins, cyclin-dependent kinases and p21 which are related with cell cycle control can be studied or clinicopathological characteristics of breast cancer patients might be evaluated in terms of p53 rs1042522 genotypes in larger population size.

Anahtar Kelimeler

• P53 gene,rs1042522,polymorphism,breast cancer

Kaynakça

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