TY - JOUR
T1 - Impact of germinal center-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population
AU - Kotani, Haruru
AU - Ito, Hidemi
AU - Kuwahara, Kazuhiko
AU - Kuzushima, Kiyotaka
AU - Iwata, Hiroji
AU - Tsunoda, Nobuyuki
AU - Nagino, Masato
AU - Matsuo, Keitaro
N1 - Funding Information:
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).
Publisher Copyright:
© 2019, The Japanese Breast Cancer Society.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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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U2 - 10.1007/s12282-019-00956-5
DO - 10.1007/s12282-019-00956-5
M3 - Article
C2 - 30810967
AN - SCOPUS:85062600563
VL - 26
SP - 562
EP - 572
JO - Breast Cancer
JF - Breast Cancer
SN - 1340-6868
IS - 5
ER -