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Impact of germinal center-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population

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Abstract

Background

Germinal center-associated nuclear protein (GANP) is a phosphoprotein involved in mRNA export and regulation of DNA recombination. Although GANP expression in human breast cancer tissue is associated with breast cancer prognosis, the association between the genetic background of GANP and susceptibility and prognosis of breast cancer is unclear.

Methods

We selected 694 breast cancer cases and 1376 age- and menopausal status-matched non-cancer controls from the Hospitable-based Epidemiologic Research Program, conducted at Aichi Cancer Center between 2001 and 2005. We evaluated the impact of two polymorphisms at the GANP locus (rs2839178 and rs11702450) on the susceptibility and prognosis of breast cancer. Reference alleles were defined as the A allele for rs2839178 and G allele for rs11702450.

Results

The GG genotype of rs2839178 was statistically significantly associated with breast cancer risk (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30–0.76, P = 0.002). In prognostic analysis, compared to those with AA genotype of rs2839178, patients with AG or GG genotypes had longer disease-free survival (DFS) (hazard ratio [HR] 0.71, 95% CI 0.49–1.04 and HR 0.42, 95% CI 013–1.42, respectively, P for trend = 0.04). eQTL analysis indicated that association with rs2839178 can be explained by the effect of rs2839173 on expression of GANP/MCM3AP.

Conclusions

The G allele of rs2839178 at the GANP locus was significantly associated with reduced breast cancer risk and longer DFS in breast cancer patients, showing a consistent direction in the association between susceptibility and clinical outcome. GANP is, therefore, important for the occurrence and progression of sporadic breast cancer.

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Acknowledgements

We thank the many doctors, nurses, and technical and administrative staff of Aichi Cancer Center Hospital for their daily administration of the HERPACC study.

Funding

This study was funded by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan (17015018, 15K08792 and 24590776) and by a Grant-in-Aid for Third-Term Comprehensive 10-Year Strategy for Cancer Control from Ministry of Health, Labour and Welfare of Japan, and Japan Agency for Medical Research and Development (15655291).

Author information

Authors and Affiliations

  1. Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Haruru Kotani & Hiroji Iwata

  2. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Haruru Kotani, Nobuyuki Tsunoda & Masato Nagino

  3. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Haruru Kotani & Keitaro Matsuo

  4. Division of Cancer Information and Control, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Hidemi Ito

  5. Division of Cancer Descriptive Epidemiology, Nagoya University Graduate School of Medicine, 5 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hidemi Ito

  6. Department of Diagnostic Pathology, Fujita Health University Graduate School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan

    Kazuhiko Kuwahara

  7. Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Kazuhiko Kuwahara & Kiyotaka Kuzushima

  8. Department of Epidemiology, Nagoya University Graduate School of Medicine, 5 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Keitaro Matsuo

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  1. Haruru Kotani
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Corresponding author

Correspondence to Hidemi Ito.

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Conflict of interest

Haruru Kotani declares that she has no conflict of interest. Hidemi Ito declares that she has no conflict of interest. Kazuhiko Kuwahara declares that he has no conflict of interest. Kiyotaka Kuzushima declares that he has no conflict of interest. Hiroji Iwata declares that he has no conflict of interest. Nobuyuki Tsunoda declares that he has no conflict of interest. Masato Nagino declares that he has no conflict of interest. Keitaro Matsuo declares that he has no conflict of interest.

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12282_2019_956_MOESM1_ESM.tif

Supplementary material 1 Supplementary fig. 1 eQTL box plot of rs2839173 GANP/MCM3AP in normal breast tissue (TIF 1590 KB)

Supplementary material 2 (XLSX 15 KB)

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Kotani, H., Ito, H., Kuwahara, K. et al. Impact of germinal center-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population. Breast Cancer 26, 562–572 (2019). https://doi.org/10.1007/s12282-019-00956-5

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  • DOI: https://doi.org/10.1007/s12282-019-00956-5

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