XRCC4

Cancer susceptibility

XRCC4 polymorphisms have been linked to a risk of susceptibility for cancers such as bladder cancer, breast cancer, prostate cancer, hepatocellular carcinoma, lymphomas, and multiple myeloma. With respect to bladder cancer, for example, the link between XRCC4 and risk of cancer susceptibility was based on hospital-based case-control histological studies of gene variants of both XRCC4 and XRCC3 and their possible association with risk for urothelial bladder cancer. The linkage with risk for urothelial bladder cancer susceptibility was shown for XRCC4, but not for XRCC3 With regard to breast cancer, the linkage with "increased risk of breast cancer" was based on an examination of functional polymorphisms of the XRCC4 gene carried out in connection with a meta-analysis of five case-control studies . There is also at least one hospital-based case-control histological study indicating that polymorphisms in XRCC4 may have an "influence" on prostate cancer susceptibility. Conditional (CD21-cre-mediated) deletion of the XRCC4 NHEJ gene in p53-deficient peripheral mouse B cells resulted in surface Ig-negative B-cell lymphomas, and these lymphomas often had a "reciprocal chromosomal translocation" fusing IgH to Myc (and also had "large chromosomal deletions or translocations" involving IgK or IgL, with IgL "fusing" to oncogenes or to IgH). XRCC4- and p53-deficient pro-B lymphomas "routinely activate c-myc by gene amplification"; and furthermore, XRCC4- and p53-deficient peripheral B-cell lymphomas "routinely ectopically activate" a single copy of c-myc. Indeed, in view of the observation by some that "DNA repair enzymes are correctives for DNA damage induced by carcinogens and anticancer drugs", it should not be surprising that "SNPs in DNA repair genes may play an important part" in cancer susceptibility. In addition to the cancers identified above, XRCC4 polymorphisms have been identified as having a potential link to various additional cancers such as oral cancer, lung cancer, gastric cancer, and gliomas.