Hereditary predisposition to breast cancer is largely affected by the mutations in the genes of the DNA repair pathways. Novel genes involved in DNA repair are therefore prospective candidates also for breast cancer susceptibility genes. The RHINO (Rad9, Rad1, Hus1-interacting nuclear orphan) gene plays a central role in DNA damage response and in cell cycle regulation. RHINO interacts with Rad9-Rad1-Hus1 (9-1-1) complex and with ATR activator TopBP1, which recruit it to the site of DNA damage. We analyzed the effects of the germline variation in RHINO on breast cancer risk. We sequenced the coding region of the RHINO gene 466 index cases of Finnish breast cancer families and in 507 population controls. The genotypes of the most likely functional variant were further determined in a large dataset of 2,944 cases and 1,976 controls. We analyzed the common variation of the RHINO locus and determined the haplotypes using five SNPs in 1,531 cases and 1,233 controls. We identified seven variants including four missense variations, a 5′ UTR variant, a silent variant, and a nonsense variant c.250C>T, R84X (rs140887418). All variants were also present in control individuals with frequencies close to those of the cases (P > 0.05). The c.250C>T variant was present in 12 breast cancer patients (0.4 %) and of 16 controls (0.8 %) with the difference not statistically significant (OR = 0.50, 95 %CI: 0.24–1.06, P = 0.066). The haplotype frequencies did not differ in cases and controls (P = 0.59). Germline variation in the RHINO gene is unlikely to influence inherited susceptibility to breast cancer.
RHINO Rad9, Rad1, Hus1-interacting nuclear orphan Breast cancer susceptibility gene Candidate gene Germline variation Genetic risk Familial breast cancer
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We thank research nurse Irja Erkkilä for assistance with data management. The Finnish Cancer Registry is acknowledged for diagnostic data. The study has been funded by the Helsinki University Central Hospital Research Fund, the Sigrid Juselius Foundation, the Finnish Cancer Society, and the Academy of Finland (132473), and for T.H. by the Finnish Cultural Foundation, Orion Farmos Research Fund, and Biomedicum Helsinki Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
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