Abstract
Background8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC.MethodsWe conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.ResultsNo significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06–2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26–2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30–2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06–4.58).ConclusionThe allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.
Highlights
Nasopharyngeal carcinoma (NPC) develops commonly in the Fossa of Rosenmuller of the nasopharynx
We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of Human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys, ITGA2 C807T and Xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms on NPC risk
No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption
Summary
Nasopharyngeal carcinoma (NPC) develops commonly in the Fossa of Rosenmuller of the nasopharynx. It is a rare malignancy in most parts of the world with an annual frequency less than 1 per 100 000 population [1]. Given the increasing incidence of NPC cases and the fact that many cases are diagnosed at an advanced stage [4], it is important to find ways of ensuring early diagnosis and prompt treatment. This is challenging as the nasopharynx is not visualized and accessed. Discovering biomarkers for NPC screening is one of the ways in which a susceptible population could be identified early, which will help physicians in early detection and treatment of NPC
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