The relationship between DNA repair failure and cancer is well established as in the case of rare, high penetrant
genes in high cancer risk families. Beside this, in the last two decades, several studies have investigated a possible association
between low penetrant polymorphic variants in genes devoted to DNA repair pathways and risk for developing
cancer. This relationship would be also supported by the observation that DNA repair processes may be modulated by sequence
variants in DNA repair genes, leading to susceptibility to environmental carcinogens. In this framework, the aim
of this review is to provide the reader with the state of the art on the association between common genetic variants and
cancer risk, limiting the attention to single nucleotide polymorphisms (SNPs) of the NBN gene and providing the various
odd ratios (ORs). In this respect, the NBN protein, together with MRE11 and RAD50, is part of the MRN complex which
is a central player in the very early steps of sensing and processing of DNA double-strand breaks (DSBs), in telomere
maintenance, in cell cycle control, and in genomic integrity in general. So far, many papers were devoted to ascertain possible
association between common synonymous and non-synonymous NBN gene polymorphisms and increased cancer
risk. However, the results still remain inconsistent and inconclusive also in meta-analysis studies for the most investigated
E185Q NBN miscoding variant.
NBN, Polymorphisms, Cancer, DNA repair, DSBs, E185Q, SNPs.
Department of Science, University Roma Tre, V.le Marconi 446, 00146 Rome, Italy.