DNA repair genes, XRCC3 and RAD51, polymorphisms and risk of childhood acute lymphoblastic leukemia

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, Türkiye

Tezin Onay Tarihi: 2010

Öğrenci: CİHAN TANRIKUT

Danışman: NURSEN ÇORUH

Özet:

In this study, the role of two DNA repair genes, X-ray repair cross complementing group 3 (XRCC3) Thr241Met and Rad51 G135C polymorphisms were investigated in the risk of development of childhood ALL in Turkish population among 193 healthy controls and 184 ALL patients, by using PCR-RFLP technique. For XRCC3 Thr241Met polymorphism, the frequencies of both heterozygous and homozygous mutant genotypes were found to be higher in the controls compared to ALL patients (OR: 0.59, p = 0.02; OR: 0.48, p = 0.02, respectively). In addition, either heterozygous (Thr/Met) or homozygous mutant (Met/Met) genotypes were significantly more common in the controls than the ALL patients (OR: 0.55, p =0.005). In case of Rad51 G135C polymorphism, no significant associations have been found with the risk of childhood ALL. Combination of XRCC3 heterozygote and Rad51 heterozygote genotypes increased the protective effect for risk of childhood ALL. (OR=0.35 ; p =0.02). Combination of homozygote mutant genotype of XRCC3 with homozygote wild type genotype of Rad51 gave a highly statistically proved protective effect for the development of disease (OR= 0.36; p= 0.004). To our knowledge, this is the first study showing the protective role of XRCC3 Thr241Met polymorphism either alone or in combination with Rad51 G135C variant on the risk of development of childhood ALL. In addition, interactions of these polymorphisms with non-genetic risk factors were investigated. Only in terms of paternal exposure, the heterozygote (Thr/Met) genotype for XRCC3 gene in children whose father exposed to cigarette smoke demonstrated a significant risk of 3.0 fold (p=0.05). Moreover, the frequency of Rad51 135C allele was determined for the first time in Turkish population. The frequency of the mutant allele was found to be very similar to that observed in other Caucasian populations.