1. Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women
- Author
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Setsuko Ishihara, Yutaka Ogasawara, Kengo Kawada, Hiroyoshi Doihara, Yoko Suzuki, Minami Hatono, Hiroshi Kawai, Takayuki Iwamoto, Yuko Abe, Hirokuni Ikeda, Naruto Taira, Keiko Nishiyama, Tadahiko Shien, Yukiko Kajiwara, Takahiro Tsukioki, Mariko Kochi, Shinichi Toyooka, Yoichi Ishibe, Kensuke Kawasaki, and Taeko Mizoo
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Estrogen receptor ,Single-nucleotide polymorphism ,Breast Neoplasms ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Gene Frequency ,Japan ,Risk Factors ,Internal medicine ,Progesterone receptor ,medicine ,Humans ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,Genetic Predisposition to Disease ,Allele ,skin and connective tissue diseases ,Alleles ,Genetic association ,Breast Density ,business.industry ,Body Weight ,Estrogen Receptor alpha ,General Medicine ,Middle Aged ,medicine.disease ,Body Height ,030104 developmental biology ,Phenotype ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Case-Control Studies ,Female ,Carcinogenesis ,business ,Receptors, Progesterone ,Estrogen receptor alpha - Abstract
Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. In previous case–control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.
- Published
- 2020