Increased expression of ERCC2 gene in head and neck cancer is associated with aggressive tumors: a systematic review and case-control study.

INTRODUCTION: The excision repair cross-complementation group 2 (ERCC2) ATP-dependent helicase is an essential member of the DNA repair pathway. It has been observed to be differentially expressed in different cancers, which shows its involvement in carcinogenesis. AIM: In the present study we have tried to determine the association of expression patterns of this gene with head and neck carcinogenesis. METHOD: We first carried out a systematic review of the available studies on the role of ERCC2 in head and neck cancer (HNC). In order to test the hypothesis that the expression patterns of XPD/ERCC2 play a critical role in HNC pathogenesis, we then conducted a population based case-control study on 81 head and neck tumor samples and adjacent normal-tissue control samples. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR) were used to assess ERCC2 deregulation at the mRNA level. RESULT: Expression analysis showed that the ERCC2 expression level was significantly upregulated (p<0.05) in HNC tissues compared with adjacent normal tissues. Furthermore, the expression pattern of ERCC2 was correlated with the expression pattern of Ki-67 and a significant correlation (r = 0.230, p<0.03) was observed between ERCC2 and Ki-67. Spearman's correlation also showed a significant correlation between ERCC2 expression and tumor stage (r = 0.271, p<0.02) and grade (r = 0.228, p<0.02) of HNC. CONCLUSIONS: Our data suggest that deregulation of ERCC2 in HNC has the potential to predict a more aggressive cancer phenotype and may be considered a possible biomarker for improved diagnosis and prognosis of HNC.

Germline variations of apurinic/apyrimidinic endonuclease 1 (APEX1) detected in female breast cancer patients.

Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein which plays a central role in the BER pathway. APEX1 gene being highly polymorphic in cancer patients and has been indicated to have a contributive role in Apurinic/apyrimidinic (AP) site accumulation in DNA and consequently an increased risk of cancer development. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 530 breast cancer patients and 395 matched healthy controls and then analyzed by single-stranded conformational polymorphism followed by sequencing. Sequence analysis revealed fourteen heterozygous mutations, seven 5'UTR, one 3 'UTR, two intronic and four missense. Among identified mutations one 5'UTR (rs41561214), one 3'UTR (rs17112002) and one missense mutation (Ser129Arg, Mahjabeen et al., 2013) had already been reported while the remaining eleven mutations. Six novel mutations (g.20923366T>G, g.20923435G>A, g.20923462G>A, g.20923516G>A, 20923539G>A, g.20923529C>T) were observed in 5'UTR region, two (g.20923585T>G, g.20923589T>G) in intron1 and three missense (Glu101Lys, Ala121Pro, Ser123Trp) in exon 4. Frequencues of 5'UTR mutations; g.20923366T>G, g.20923435G>A and 3'UTR (rs17112002) werecalculated as 0.13, 0.1 and 0.1 respectively. Whereas, the frequency of missense mutations Glu101Lys, Ser123Trp and Ser129Arg was calculated as 0.05. A significant association was observed between APEX1 mutations and increased breast cancer by ~9 fold (OR=8.68, 95%CI=2.64 to 28.5) with g.20923435G>A (5'UTR) , ~13 fold (OR= 12.6, 95%CI=3.01 to 53.0) with g.20923539G>A (5'UTR) and~5 fold increase with three missense mutations [Glu101Lys (OR=4.82, 95%CI=1.97 to 11.80), Ser123Trp (OR=4.62, 95%CI=1.7 to 12.19), Ser129Arg (OR=4.86, 95%CI=1.43 to 16.53)]. The incidence of observed mutations was found higher in patients with family history and with early menopause. In conclusion, our study demonstrates a significant association between germ line APEX1 mutations and breast cancer patients in the Pakistani population.