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

  • Epidemiology
  • Published:
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Abstract

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.

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Abbreviations

SNP:

Single nucleotide polymorphism

5′-UTR:

5-Untranslated region

OR:

Odds ratio

CI:

Confidence interval

BMI:

Body mass index

TNBC:

Triple negative breast cancer

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Acknowledgments

We are grateful to Dr. Huimei Chen and Dr. Yimei Fan (Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China) and Prof. Peter Propping for their valuable advice on this work. This work was partly supported by the National Natural Science Foundation of China (grant number: 30800546 and 30972535); the Doctoral Foundation of Education Ministry of China (grant number: 20070284015); Natural Science Foundation of Jiangsu Province, China (grant number: BK2008269); the Jiangsu Science and Technology Foundation (grant number: BZ2008055) and the Jiangsu Province Institute of Cancer Research Foundation (grant number: ZQ200703).

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Authors and Affiliations

  1. Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, 210093, China

    Xiaoxiang Chen, Jingmei Wang, Wenwen Guo, Xiufang Liu, Caixia Sun, Zhenming Cai, Yimei Fan & Yaping Wang

  2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, China

    Xiaoxiang Chen, Jingmei Wang, Wenwen Guo, Xiufang Liu, Caixia Sun, Zhenming Cai, Yimei Fan & Yaping Wang

  3. Department of Gynecologic Oncology, Jiangsu Institute of Cancer Research, Nanjing, China

    Xiaoxiang Chen

  4. Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University School of Medical, Nanjing, China

    Jingmei Wang

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  1. Xiaoxiang Chen
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Correspondence to Yaping Wang.

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Chen, X., Wang, J., Guo, W. et al. Two functional variations in 5′-UTR of hoGG1 gene associated with the risk of breast cancer in Chinese. Breast Cancer Res Treat 127, 795–803 (2011). https://doi.org/10.1007/s10549-010-1284-2

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  • DOI: https://doi.org/10.1007/s10549-010-1284-2

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