The HDL-associated paraoxonase (PON) activities play a role in decreasing oxidative stress, which is known to contribute to cancer development. The aim of this study was to examine the relation between the PON1 L55M and Q192R polymorphisms and breast cancer (BC) risk in Egyptian females and to analyze their relation to clinicopathological parameters of BC. Both polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, using DNA from peripheral blood in a case control study. With respect to PON1 L55M, the mutated allele (M) frequency was found in 70.5% in BC patients and in 53.5% in controls; the M allele was significantly associated with an increased risk of BC (adjusted odds ratio (OR(adj)) 2.07, 95% confidence interval (95% CI) 1.37-3.13; P = 0.011). The homozygous mutant genotype (MM) significantly increased the risk of BC (OR(adj) 2.07, 95% CI 1.17-3.64, P = 0.011). However, as regard PON1 Q192R, the R mutated allele frequency was found in 28.5% in BC patients and in 33% in controls, the women who were QR heterozygotes (OR(adj) 0.96, 95% CI 0.55-1.68) or RR homozygotes (OR(adj) 0.64, 95% CI 0.25-1.63), and R allele (OR(adj) 0.81, 95% CI 0.53-1.42) did not show any risk for BC. Both PON1 L55M and Q192R polymorphisms genotype frequencies were not related to patient's age (P = 0.94 and 0.72, respectively). M allele genotypes (LM/MM) carriers showed significant association only with nodal metastases (P = 0.02) but not with other clinicopathologic parameters. However, R allele genotype (QR/RR) carriers showed insignificant correlation with clinicopathological parameters. In conclusion, our results suggest that the M allele of L55M polymorphism could be a suitable marker for BC susceptibility and tumor prognosis in Egyptian women.

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The genes involved in DNA repair system play a crucial role in the protection against mutations. It has been hypothesized that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer (BC). The aim of the present study was to evaluate the association of genetic polymorphisms in 2 DNA repair genes, XPD (Asp312Asn) and XRCC1 (A399G), with BC susceptibility. We further investigated the potential combined effect of these DNA repair variants on BC risk. Both XPD (xeroderma pigmentosum group D) and XRCC1 (X-ray repair cross-complementing group 1) polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method and PCR with confronting two-pair primers (PCR-CTPP), using DNA from peripheral blood in a case control study. Our results revealed that the frequencies of AA genotype of XPD codon 312 polymorphism were significantly higher in the BC patients than in the normal individuals (P ≤ 0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing BC. Also, no association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease. Finally, the combination of AA(XPD) + AG(XRCC1) were significantly associated with BC risk. Our results suggested that, XPD gene is an important candidate gene for susceptibility to BC. Also, gene-gene interaction between XPD(AA) + XRCC1(AG) polymorphism may be associated with increased risk of BC in Egyptian women.

This study aimed to evaluate the clinical reliability and accuracy of two MAGE transcripts (MAGE-A3, MAGE-A4 mRNA) in the peripheral blood (PB) of patients with breast cancer (BC), and to evaluate their potential limits and utility to detect BC. We aimed also to analyze their relation to clinicopathological characteristics of the tumor. This study is a prospective, controlled, double-blinded study conducted on 100 BC women and 100 age-matched control women. There were 52 patients with localized breast mass with no evidence of nodal affection or distant metastases and 48 patients suffering from metastatic BC. MAGE-A3 and MAGE-A4 mRNA in the PB were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR). None of the control women was positive for either MAGE-A3, MAGE-A4. In BC women, positivity for MAGE-A3 in PB was observed in 37 patients (37%), and MAGE-A4 positivity was observed in 11 patients (11%); with 100% specificity for both transcripts. The presence of MAGE-A3 was significantly associated with nodal status (P = 0.009), tumor size (P = 0.009), and American Joint Committee on Cancer stage (P = 0.009), whereas MAGE-A4 positivity was significantly associated with histological grade (P = 0.020). RT-PCR assays of MAGE-A3 and MAGE-A4 in the PB of BC patients may have prognostic and predictive implications, and they are promising specific tumor markers of BC.