Two functional variations in 5'-UTR of hoGG1 gene associated with the risk of breast cancer in Chinese

8-Hydroxy-2'-deoxyguanine (8-OHdG) is produced by the oxidative stress-induced damage in DNA, which could pair with adenine (A) during DNA replication, leading to G-T transversion mutations. Glycosylase hOGG1 can recognize and excise oxidized guanines from duplex DNA. This work aims to investigate the relationship between the functional variations in 5-untranslated region (5'-UTR) of hOGG1 gene and the risk of breast cancer. Genotypes were analyzed in 518 sporadic breast cancer patients and 777 health controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Risk-stratified subgroup analysis was performed to reveal the associations between the detected variations and the risk of characteristic breast cancer. In addition, immunohistochemistry was carried out to assess the functional effect of these variations on hOGG1gene expression. Five variations in 5'-UTR of hOGG1 gene are found in this study. Three of them, c.-18G > T, c.-23A > G, and c.-53G > C, are known single nucleotide polymorphisms, the other two, c.-45G > A and c.-63G > C, are rare variations. The frequency of c.-18G/T and c.-53G/C was significantly higher in breast cancer patients than those in healthy controls (P = 0.03, OR 2.01, 95% CI 1.04-3.90; and P = 0.01, OR 2.43, 95% CI 1.17-5.04, respectively). Both variations were especially prevalent in premenopausal status, and in the triple (estrogen receptor, progesterone receptor, and human epidermal growth factor Receptor 2) negative subgroups, respectively. Moreover, the variation of c.-18G > T could cause a reduced expression of hOGG1 gene.