Significant association of XRCC4 single nucleotide polymorphisms with childhood leukemia in Taiwan.
ABSTRACT The DNA repair gene XRCC4, a member of the protein family involved in non-homologous end-joining repair pathway, plays a major role in repairing DNA double-strand breaks. XRCC4 is important in maintaining the overall genome stability, and it is also thought to play a key role in human carcinogenesis. We investigated some novel polymorphic variants of XRCC4, including C-1622T (rs7727691), G-1394T (rs6869366), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317), and analyzed the association of specific genotype with susceptibility to childhood leukemia.
In total, 266 children with leukemia and 266 age-matched healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped investigating the association of these polymorphisms with childhood leukemia.
We found differences in frequency of the XRCC4 G-1394T and intron 3 genotype, but not the XRCC4 codon 247, or intron 7, between the childhood leukemia and control groups. Our data indicated the G allele of G-1394T and deletion of intron 3 are clear risk factors of susceptibility to childhood leukemia (p=0.0022 and 0.0075). As for XRCC4 C-1622T and C-571T, there was no difference in the distribution between the two groups. The analysis of joint effect for XRCC4 G-1394T and intron 3 showed that individuals with GT at G-1394T and DD at intron 3 present the highest potential for developing childhood leukemia than other groups (odds ratio=4.94, 95% confidence interval=1.01-24.27, p=0.0404).
Our findings suggest that the G allele of XRCC4 G-1394T and deletion of intron 3 may be responsible for childhood leukemia and may be useful in early detection of child leukemia.
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ABSTRACT: Acute myeloid leukemia (AML) is the most common type of adult leukemia for which cytosine arabinoside-based chemotherapy is the main treatment. Single nucleotide polymorphisms within the nucleotide excision repair pathway may alter the susceptibility of leukemia cells to chemotherapy. We investigated the roles of six single nucleotide polymorphisms (ERCC5rs76871136, ERCC5rs77569659, ERCC5rs873601, XPCrs2228000, XPCrs2228001, and XPCrs1870134) in the nucleotide excision repair pathway in influencing the outcome of patients with AML treated with cytosine arabinoside-based chemotherapy. One hundred fifty-one patients with AML in a Chinese population were enrolled in this study. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We found that the distribution of three genotypes of XPCrs1870134 significantly differed in the cytogenetic risk groups (P = 0.04). A statistically significant correlation between polymorphisms of XPCrs2228001 and gender was found among the gender groups (P = 0.03). Moreover, patients carrying at least one variant allele (XPCrs2228001AA+CC) were more likely to respond better than those who did not carry a variant. However, no significant association was detected between polymorphisms in ERCC5 and treatment response. These findings suggest that XPC polymorphisms are important markers for the outcome of patients with AML in the Chinese population.International journal of hematology 09/2012; 96(4):450-60. · 1.17 Impact Factor
- 11/2011; , ISBN: 978-953-307-697-3