OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data

• Published in: Disease markers Vol. 2015; no. 2015; pp. 1 - 16
• Main Authors: Mehmood, Humera, Sabir, Maimoona, Mahjabeen, Ishrat, Ali, Kashif, Kayani, Mahmood Akhtar
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2015; John Wiley & Sons, Inc
• Subjects: Adult; Breast cancer; Breast Neoplasms - genetics; Development and progression; DNA Glycosylases - genetics; DNA Mutational Analysis - methods; Female; Gene expression; Gene mutations; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Germ-Line Mutation; Health aspects; Humans; Middle Aged; Pakistan; Pakistan
• ISSN: 0278-0240; 1875-8630; 1875-8630
• DOI: 10.1155/2015/690878

In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3′UTR mutations, three missense mutations, and a nonsense mutation. Significantly (p<0.001) increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3′UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (p<0.009). Similarly ~14-fold increased risk was associated with Val159Gly (p<0.01), ~17-fold with Gly221Arg (p<0.005), and ~18-fold with Ser326Cys (p<0.004) in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold (p<0.01) increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer.