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27.02.2019 | Original Article

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

Zeitschrift:
Breast Cancer
Autoren:
Haruru Kotani, Hidemi Ito, Kazuhiko Kuwahara, Kiyotaka Kuzushima, Hiroji Iwata, Nobuyuki Tsunoda, Masato Nagino, Keitaro Matsuo
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12282-019-00956-5) contains supplementary material, which is available to authorized users.

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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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Zusatzmaterial
Supplementary material 1 Supplementary fig. 1 eQTL box plot of rs2839173 GANP/MCM3AP in normal breast tissue (TIF 1590 KB)
12282_2019_956_MOESM1_ESM.tif
Supplementary material 2 (XLSX 15 KB)
12282_2019_956_MOESM2_ESM.xlsx
Literatur
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