Prognostic impact of a single-nucleotide polymorphism near the CTSO gene in hormone receptor-positive breast cancer patients.
BACKGROUND
Tamoxifen can reduce the occurrence of breast cancer by a half in high-risk women. Recently, a genome-wide association study identified two single-nucleotide polymorphisms (SNPs) near or in the CTSO and ZNF423 genes that were associated with breast cancer risk during tamoxifen therapy. We hypothesized that these two SNPs could be associated with increased recurrence in breast cancer patients who received adjuvant tamoxifen therapy.


METHODS
A total of 586 breast carcinomas were available for SNP genotyping assays. TaqMan pre-designed SNP genotyping assays were used to identify the presence of CTSO rs10030044 and ZNF423 rs8060157. We then investigated the relationship between CTSO rs10030044 genotypes and mRNA expression levels of CTSO and BRCA1 in 290 breast cancer patients.


RESULTS
We found a positive correlation between the variant GG genotype of CTSO rs10030044 and shorter disease-free survival, or overall survival in hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy. In contrast, this genotype was not associated with prognosis in hormone receptor-negative breast cancer patients. Multivariate Cox regression analysis revealed that this genotype was an independent factor indicating a poor prognosis in hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy. No association was found between CTSO genotype and mRNA expression of CTSO and BRCA1. ZNF423 rs8060157 genotype was not associated with prognosis in this study.


CONCLUSIONS
We show that a SNP near the CTSO gene is a poor prognostic factor in breast cancer although further research might help to reveal the factors linking this genotype and prognosis.
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Yukari
Y
Hato
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Naoto
N
Kondo
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Nobuyasu
N
Yoshimoto
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Yumi
Y
Endo
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Tomoko
T
Asano
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Yu
Y
Dong
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Mayumi
M
Nishimoto
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Satoru
S
Takahashi
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Yoshitaka
Y
Fujii
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Ryoichi
R
Nakanishi
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. t.toyama@med.nagoya-cu.ac.jp.
Tatsuya
T
Toyama
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D002403:Cathepsins / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D019313:BRCA1 Protein; D002403:Cathepsins; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C492913:BRCA1 protein, human; C031017:ornithine decarboxylase antizyme; C508053:ERBB2 protein, human; C534179:CTSO protein, human
Breast cancer; CTSO; Estrogen receptor; Hormone receptor; Polymorphism; Tamoxifen