RINT1 – Breast Cancer

RINT1 has been proposed as an intermediate-penetrance, autosomal dominant breast cancer susceptibility gene following exome sequencing in a multiple-case family that identified three likely pathogenic variants (c.343C>T (p.Gln115Ter), c.1132_1134del (p.Met378del), c.1207G>T (p.Asp403Tyr)) absent from public databases. Population-based screening detected 23 carriers in 1,313 early-onset breast cancer cases versus 6 in 1,123 controls (OR 3.24; 95% CI 1.29–8.17; P = 0.013) (PMID:25050558), and four additional carriers were found among probands from 798 multiple-case families.

However, a follow-up study sequencing RINT1 in 2,024 familial breast cancer cases and 1,886 matched controls found a similar frequency of rare truncating and missense variants in cases (28/2024, 1.38%) and controls (27/1886, 1.43%; P > 0.999) with no difference in Lynch syndrome–spectrum cancer incidence among carrier families (PMID:27544226). These conflicting data dispute a moderate-penetrance role for RINT1 in breast cancer predisposition and underscore the need for larger studies before clinical implementation. Key take-home: current evidence does not support RINT1 variant screening for breast cancer risk prediction.

References

• Cancer discovery • 2014 • Rare mutations in RINT1 predispose carriers to breast and Lynch syndrome-spectrum cancers. PMID:25050558
• Breast cancer research and treatment • 2016 • Reevaluation of RINT1 as a breast cancer predisposition gene. PMID:27544226

Evidence Based Scoring (AI generated)