Fanconi anemia (FA) is a rare genetically heterogeneous disorder associated
with bone marrow failure, birth defects and cancer susceptibility. Apart from
the disease- causing mutations in FANC genes, the identification of specific
DNA variations, such as single nucleotide polymorphisms (SNPs), in other
candidate genes may lead to a better clinical description of this condition
enabling individualized treatment with improvement of the prognosis. In this
study, we have assessed 95 SNPs located in 52 key genes involved in base
excision repair (BER), nucleotide excision repair (NER), mismatch repair
(MMR), double strand break (DSB) repair and cell cycle control using a DNA
repair chip (Asper Biotech, Estonia) which includes most of the common
variants for the candidate genes. The SNP genotyping was performed in five
FA-D2 patients and in one FA-A patient. The polymorphisms studied were
synonymous (n=10), nonsynonymous (missense) (n=52) and in non-coding regions
of the genome (introns and 5 ?and 3? untranslated regions (UTR)) (n=33).
Polymorphisms found at the homozygous state are selected for further
analysis. Our results have shown a significant inter-individual variability
among patients in the type and the frequency of SNPs and also elucidate the
need for further studies of polymorphisms located in ATM, APEX APE 1, XRCC1,
ERCC2, MSH3, PARP4, NBS1, BARD1, CDKN1B, TP53 and TP53BP1 which may be of
great importance for better clinical description of FA. In addition, the
present report recommends the use of SNPs as predictive and prognostic
genetic markers to individualize therapy of FA patients.
Tagging Single Nucleotide Polymorphisms in Cell Cycle Control Genes and Susceptibility to Invasive Epithelial Ovarian Cancer