OGG1 gene sequence variation in head and neck cancer patients in Pakistan.
In Pakistani culture tobacco use is very high and a well known risk factor for developing head and neck cancer (HNC), tobacco smoke containing high quantities of chemical carcinogens such as aromatic amines and reactive oxygen species. OGG1 is the primary enzyme in the base excision repair (BER) pathway, responsible for the excision of 7, 8-dihydro-8-oxoguanine, a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species. Groups of 300 already diagnosed HNC patients along with normal controls were included in this study. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the whole coding region of OGG1 gene. Sequence analysis revealed eight novel mutations (six missense and two frame shift mutations). Frequencies of missense mutations, Asp267Asn, Ser279Gly and Ile253Phe were 0.12, 0.13 and 0.06 respectively. Frequencies of other missense mutations, 1578A> T, 1582C> T and Ala399Glu (1542C> A) were 0.13, 0.13 and 0.16, whereas values for the frame shift mutations 1582insG and 1543-1544delCT were 0.13 and 0.16. In our study, incidence of these mutations was found higher in oral cancers (p<0.002) and in smokers (p<0.002) when compared with other sites of HNC and nonsmokers, respectively. Our finding suggests that these germline mutations in OGG1 gene contribute to risk of developing HNC.
Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
Ishrat
I
Mahjabeen
Ruqia Mehmood
RM
Baig
Nosheen
N
Masood
Maimoona
M
Sabir
Faraz Arshad
FA
Malik
Mahmood Akhtar
MA
Kayani
D001483:Base Sequence; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D018095:Germ-Line Mutation / Q000187:drug effects / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010154:Pakistan; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000009:adverse effects*; D014029:Tobacco Use Disorder
D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human