14q32.33

No human disease has been linked to inactivation of XRCC3. However, polymorphisms in XRCC3 may be associated with increased cancer risk (see below).

Genetic Epidemiology:
The most frequent polymorphism in XRCC3 is XRCC3 C18067T which results in a Thr to Met amino acid substitution at codon 241. Carriers of the variant T-allele of XRCC3 T241M have higher DNA adduct levels in lymphocyte DNA compared to homozygous C-allele carriers, indicating that the polymorphism is associated with lowered DNA repair capacity. The variant allele of XRCC3 T241M polymorphism has been associated with increased risk of squamous cell carcinoma of the head and neck in one study while another study found no association. No association has previously been found with colon cancer, non-melanoma skin cancer, prostate cancer, gastric cancer, ovarian cancer. Conflicting results have been published on the association with breast cancer, bladder cancer, malignant melanoma and lung cancer.
Two frequent SNP are upstream of XRCC3 T241M have also been studied, namely XRCC3 A4541G and XRCC3 A17897G. Neither polymorphism gives rise to amino acid changes. The variant allele of A17897G has been associated with decreased risk of breast cancer and ovarian cancer. The same tendency, but no significant associations was found for lung cancer.
XRCC3 A4541G was not associated to risk of breast cancer or lung cancer. However, homozygote carriers of the variant allele had lower risk of serous epithelial ovarian cancer.