Elsevier

The Breast

Volume 22, Issue 5, October 2013, Pages 707-712
The Breast

Original article
Genetic polymorphism in hOGG1 is associated with triple-negative breast cancer risk in Chinese Han women

https://doi.org/10.1016/j.breast.2012.12.016Get rights and content

Abstract

8-hydroxy-2′-deoxyguanine (8-OHdG), a typical product of oxidative stress-induced DNA damage, can cause a G–T transversion during DNA replication if it is not removed. Human 8-oxoguanine glycosylase 1 (hOGG1), a key DNA repair gene, recognizes and excises 8-OHdG from damaged DNA accurately; however, a c.977C>G (Ser326Cys) polymorphism in hOGG1 can inhibit the gene's ability to remove 8-OHdG. The aim of present study was to investigate the association between the c.977C>G polymorphism in hOGG1 and the risk of breast cancer in Chinese Han women. We used high-resolution melting and sequencing to analyze the genotypes of 630 patients with sporadic breast cancer patients and 777 healthy controls. We also performed risk-stratified subgroup analyses to determine the association between the c.977C>G polymorphism and other characteristics of breast cancer subgroups. Breast cancer patients and healthy controls did not have significantly different of c.977C/G genotypes (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.82–1.49, p = 0.57) and c.977G/G genotypes (OR = 1.34, 95% CI = 0.97–1.84, p = 0.09). However, the c.977G/G genotype was especially prevalent in breast cancer patients who were younger than 55 years (OR = 1.58, 95% CI = 1.05–2.39, p = 0.04), were premenopausal status (OR = 1.87, 95% CI = 1.14–3.06, p = 0.02), had triple-negative disease (OR = 2.14, 95% CI = 1.06–4.29, p = 0.04), or p53-positive disease (OR = 1.56, 95% CI = 1.14–2.12, p = 0.005). These findings suggest that the c.977C>G polymorphism in hOGG1 is associated with an increased risk of breast cancer in Chinese Han women who are younger than 55 years, premenopausal, triple-negative, or p53-positive subgroups.

Section snippets

Background

Breast cancer is one of the most common malignancies in women worldwide today, with an estimated 1.38 million new cases and 458,000 deaths in 2008, mostly in Europe and the United States.1 The morbidity and mortality of breast cancer have increased tremendously in many developing countries.2 Among women in China, breast cancer is the most prevalent cancer and the sixth leading cause of death.3 Known risk factors for breast cancer include family or personal history of cancer, nulliparous, and

Study population

We recruited 630 unrelated Chinese Han breast cancer patients at Jiangsu Cancer Hospital between December 2007 and December 2010. All subjects were newly diagnosed and had been confirmed by one pathologist. Peripheral blood samples were collected before the patients underwent treatment.

We recruited 777 healthy controls for routine health examinations at Jiangsu Cancer Hospital that included a detailed interview, abdominal ultrasonography, cardiogram, chest X-ray, and hepatic function, fasting

Study population

A total of 630 patients diagnosed with breast cancer and 777 controls were included in this study. The mean ages (±SDs) of the breast cancer patients and healthy controls were 50.24 ± 12.84 years and 50.50 ± 12.84 years, respectively. The clinical characteristics of the patients included in the present study are summarized in Table 1. For the menopausal status, in breast cancer patients, 52.4% were postmenopausal, 47.6% were premenopausal. In healthy controls, 49.8% were postmenopausal, 50.2%

Discussion

In this case–control study, we genotyped a functional SNP (c.977C>G) of hOGG1 gene in breast cancer in Chinese Han population. We found that the c.977C>G polymorphism in hOGG1 confers an increased risk of triple-negative, p53-positive breast cancer in premenopausal Han Chinese women younger than 55 years.

Five to ten percent of breast cancer cases are believed to be hereditary and associated with certain gene mutations, such as mutations in BRCA1 and BRCA2.32 Germline mutations in these genes,

Conflict of interest

The authors declare no conflicts of interests.

Acknowledgements

This work was partly supported by the Medical Science and Technology Development Foundation, Nanjing Department of Health (grant number: QYK11140); the Jiangsu Province Institute of Cancer Research Foundation (grant number: ZK201203), and the International Exchange Support Program of Jiangsu Health (2012).

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