Rad50 interactor 1 (RINT1) has recently been reported as an intermediate-penetrance (odds ratio 3.24) breast cancer susceptibility gene, as well as a risk factor for Lynch syndrome. The coding regions and exon-intron boundaries of RINT1 were sequenced in 2024 familial breast cancer cases previously tested negative for BRCA1, BRCA2, and PALB2 mutations and 1886 population-matched cancer-free controls using HaloPlex Targeted Enrichment Assays. Only one RINT1 protein-truncating variant was detected in a control. No excess was observed in the total number of rare variants (truncating and missense) (28, 1.38 %, vs. 27, 1.43 %. P > 0.999) or in the number of variants predicted to be pathogenic by various in silico tools (Condel, Polyphen2, SIFT, and CADD) in the cases compared to the controls. In addition, there was no difference in the incidence of classic Lynch syndrome cancers in RINT1 rare variant-carrying families compared to RINT1 wild-type families. This study had 90 % power to detect an odds ratio of at least 2.06, and the results do not provide any support for RINT1 being a moderate-penetrance breast cancer susceptibility gene, although larger studies will be required to exclude more modest effects. This study emphasizes the need for caution before designating a cancer predisposition role for any gene based on very rare truncating variants and in silico-predicted missense variants.
基金:
National Breast Cancer Foundation; Cancer Australia; Victorian Cancer Agency; National Health and Medical Research Council of Australia; National Breast Cancer Foundation [PD-16-02, IF-15-004, PF-13-10] Funding Source: researchfish
第一作者单位:[1]Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, 305 Grattan St, Melbourne, Vic 3000, Australia[2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Canc Biol Med Ctr,Wuhan,Hubei,Peoples R China
通讯作者:
通讯机构:[1]Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, 305 Grattan St, Melbourne, Vic 3000, Australia[6]Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia[11]Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia
推荐引用方式(GB/T 7714):
Li Na,Thompson Ella R.,Rowley Simone M.,et al.Reevaluation of RINT1 as a breast cancer predisposition gene[J].BREAST CANCER RESEARCH AND TREATMENT.2016,159(2):385-392.doi:10.1007/s10549-016-3944-3.
APA:
Li, Na,Thompson, Ella R.,Rowley, Simone M.,McInerny, Simone,Devereux, Lisa...&Campbell, Ian G..(2016).Reevaluation of RINT1 as a breast cancer predisposition gene.BREAST CANCER RESEARCH AND TREATMENT,159,(2)
MLA:
Li, Na,et al."Reevaluation of RINT1 as a breast cancer predisposition gene".BREAST CANCER RESEARCH AND TREATMENT 159..2(2016):385-392