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

Abstract EN

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.