ABSTRACT
Background: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common cancers that contribute to 20%–40% of all cancer incidences in India. Indian patients with HNSCC are mostly associated with tobacco usage and may have different genetic alterations compared with Western patients who are mostly associated with human papillomavirus infection. Polymorphisms in DNA repair genes are correlated to individuals' susceptibility and progression of cancer. XRCC1 is a DNA repair enzyme. Materials and Methods: In the present prospective study, Indian population of HNSCC patients (n = 45) were screened for Arg399Gln variant of XRCC1 using polymerase chain reaction-restriction fragment length polymorphism technique, prospective evaluation of the patients was done after treatment, and the single-nucleotide polymorphism results were correlated to survival functions. Results: Out of 45 patients, 28 patients were Arg/Arg, 12 patients were Arg/Gln, and 5 patients were Gln/Gln. Overall survival for the entire cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 36.3 (95% confidence interval [CI]: 33–39.5), 38.6 (95% CI: 35.3–41.9), 35.8 (95% CI: 28.6–42.9), and 26.4 (95% CI: 13.7–39.1) months (P = 0.097), respectively. Progression-free survival (PFS) of the entire patient cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 35.2 (95% CI: 31.4–39.1), 38.2 (95% CI: 34.3–42.1), 32.7 (95% CI: 26.2–39.1), and 22.3 (95% CI: 9.4–35.3) (P = 0.061), respectively. Conclusions: This study suggests that HNSCC patients with Gln substitution in place of Arg at position 399 (both homozygous and heterozygous) in XRCC1 protein have significantly inferior survival functions, higher recurrence rate, and events after radical treatment
ABSTRACT
PURPOSE: This study aims to assess a meta‑analysis of the association of X‑ray repair cross‑complementing group 1 (XRCC1) polymorphisms with the risk of various non‑carcinogenic diseases in different population. MATERIALS AND METHODS: This meta‑analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian). RESULTS: Pooled results showed no correlation between Arg194Trp and non‑carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86‑1.44) model in Asian population and dominant (OR = 1.04, 95% CI: 0.66‑1.63) model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86‑1.35) model of Asian population and quite well‑correlation with recessive (OR = 1.49, 95% CI: 1.19‑1.88), dominant (OR = 1.23, 95% CI: 0.94‑1.62), and additive (OR = 1.23, 95% CI: 0.94‑1.62) models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74‑1.51). CONCLUSION: The present meta‑analysis correspondingly shows that Arg399Gln variant to be associated with increased non‑carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non‑carcinogenic diseases.