Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met Gene Polymorphisms with Increased Risk of Head and Neck Cancer

Abstract

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI= 3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

Polymorphisms of Homologous RecombinationRAD51,RAD51B,XRCC2, andXRCC3Genes and the Risk of Prostate Cancer

“…It was found that the RAD51 polymorphism rs1801320 is associated with an elevated risk of breast [ 20 – 22 ] and triple-negative breast cancer [ 23 ] and ovarian [ 24 , 25 ], endometrial [ 26 – 28 ], colorectal [ 9 , 29 , 30 ], gastric [ 31 ], and head and neck cancer [ 32 , 33 ] and myelodysplastic syndrome [ 34 ], as well as keratoconus and Fuchs endothelial corneal dystrophy [ 35 ]. The significance of the RAD51 polymorphism rs1801320 has been best characterized in patients with breast cancer, especially in carriers of BRCA2 gene mutations.…”

“…No correlation was found between the presence of the RAD51 rs1801321 polymorphism and the risk of developing endometrial and ovarian cancer [ 28 , 42 ]. However, the variant c. -61G>T in the RAD51 gene seems to affect the development of breast and triple-negative breast cancer, acute myeloid leukemia, and head and neck cancer [ 32 , 43 – 46 ].…”

Methylation of RAD51B, XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory signature in squamous cell carcinoma of the head and neck, lung and cervix

“…RAD51B and XRCC3 are involved in homologous recombination, DNA sensing and apoptosis induction [15],[16],[17]. RAD51B and XRCC3 polymorphisms have been identified as a risk factor for prostate, ovarian, breast, head and neck and other cancer types [18],[19],[20]. In HNSCC, RAD51B is among the integration sites for HPV DNA, leading to an inactive form of the protein [21].…”

Association between XRCC3 Thr241Met polymorphism and risk of osteosarcoma in a Chinese population

“…Several recent studies have investigated the association between XRCC3 Thr241Met polymorphism and different types of cancers, but the results are contradictory. Some studies have found that XRCC3 Thr241Met polymorphism is associated with a high risk of cancer, such as glioma, hepatocellular carcinoma, colorectal cancer, breast cancer, head and neck cancer and gastric cancer (Duan et al, 2013;Luo et al, 2013;Kayani et al, 2014;Nissar et al, 2014;Qureshi et al, 2014). Duan and colleagues investigated the role of XRCC3 Thr241Met polymorphism in hepatocellular carcinoma, and reported that the Met/Met and Thr/Met+Met/Met genotypes were significantly associated with hepatocellular carcinoma in a Chinese population (Duan et al, 2013).…”