Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India

Abstract

Squamous cell carcinoma of head and neck (SCCHN) is the sixth most common cancer globally, and in India, it accounts for 30% of all cancer cases. Epidemiological studies have shown a positive association between defective DNA repair capacity and SCCHN. The underlying mechanism of their involvement is not well understood. In the present study, we have analyzed the relationship between SCCHN and the expression of DNA repair genes namely X-ray repair cross-complementing group 1 (XRCC1), xeroderma pigmentosum group D (XPD), and 8-oxoguanine DNA glycosylase (OGG1) in 75 SCCHN cases and equal number of matched healthy controls. Additionally, levels of DNA adduct [8-hydroxyguanine (8-OHdG)] in 45 SCCHN cases and 45 healthy controls were also determined, to ascertain a link between mRNA expression of these three genes and DNA adducts. The relative expression of XRCC1, XPD, and OGG1 in head and neck cancer patients was found to be significantly low as compared to controls. The percent difference of mean relative expression between cases and controls demonstrated maximum lowering in OGG1 (47.3%) > XPD (30.7%) > XRCC1 (25.2%). A negative Spearmen correlation between XRCC1 vs. 8-OHdG in cases was observed. In multivariate logistic regression analysis (adjusting for age, gender, smoking status, and alcohol use), low expression of XRCC1, XPD, and OGG1 was associated with a statistically significant increased risk of SCCHN [crude odds ratios (ORs) (95%CI) OR 2.10; (1.06-4.17), OR 2.76; (1.39-5.49), and 5.24 (2.38-11.52), respectively]. In conclusion, our study demonstrated that reduced expression of XRCC1, XPD, and OGG1 is associated with more than twofold increased risk in SCCHN.

Polymorphisms in DNA Repair Genes and Risk of Glioma and Meningioma

“…The rs25487 located in the region of the BRCT1 binding domain, and mutations in the BRCT1 domain of BRCA1 have been implicated in the altered function of this tumor suppressor gene (Sterpone et al, 2010). Previous several studies have shown that XRCC1 399 variant allele was associated with increased gene expression of various cancers, such as head and neck cancer, ovarian cancer and hepatocellular carcinoma (Cheng et al, 2012;Kumar et al, 2012;Yuan et al, 2012). The results of our study are in line with previous studies, suggesting a strong increased risk of glioma among individuals carrying with XRCC1 399G/G or XRCC1 194T/T genotypes.…”

Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells

“…Evaluation of the combined effect of a panel of DNA repair genes that interact in different DNA repair pathways may amplify the effects of individual variation in expression level and enhance predictive power. Although reduced expression of DNA repair genes has been shown to be associated with squamous cell carcinoma of head and neck (Kumar et al, 2012) and smoking-related cancers such as lung cancer (Wei et al, 1996); few studies have evaluated the expression level of DNA repair genes in the etiology of cervical cancer. Hence, we measured the relative expression levels of NER genes (ERCC1, ERCC2, and ERCC4) and BER gene (XRCC1) in SiHa cells on treatment with Noni alone, Cisplatin alone, and combination of both Noni and Cisplatin for 24 hours.…”

“…Notably, recent clinical evidence suggests that ERCC1 levels predict response to platinum-based therapies in nonsmall cells lung cancer (Olaussen et al, 2007) and bladder cancer (Bellmunt et al, 2007). Reduced expression of ERCC2 has been reported in squamous cell carcinoma of head and neck (Kumar et al, 2012). Chinese hamster cell lines defective in ERCC4 were found to be hypersensitive not only to UV but also to DNA interstrand cross-linking agents .…”

“…Synthesis of cDNA was carried out by using cDNA synthesis kit (Fermentas Life Sciences, New Delhi, India) as per manufacturer's protocol (Kumar et al, 2012).…”

“…expression of ERCC2 has been reported in squamous cell carcinoma of head and neck (Kumar et al, 2012). These reports suggest that DNA repair genes could be involved in cervical cancer, especially as HPV is necessary but not sufficient for cervical cancer formation; and genomic instability/host genetic background often participate in its development and progression as they influence HPV acquisition and persistence (Bajpai et al, 2013).…”