ROPN1L – Breast Cancer

This summary evaluates the association between ROPN1L (HGNC:24060) and breast cancer (MONDO_0007254) based on two independent genome‑wide association studies. The first study screened 906,600 SNPs in a cohort including 348 breast cancer cases and 348 controls and advanced several candidate loci, including ROPN1L, although joint analysis did not reach genome‑wide significance (PMID:21424380). The second study, conducted in a Korean population with 6,322 cases and 5,897 controls, also identified ROPN1L among seven replicated loci associated with an increased risk for breast cancer (PMID:22452962).

Assessing the clinical validity, the overall gene‑disease association is categorized as Limited. This conclusion is based on the observation that although independent cohorts reported statistical associations, the effect sizes are modest and one of the studies did not achieve genome‑wide significance after correction (PMID:21424380; PMID:22452962). The genetic evidence is derived from multi‑stage analyses where thousands of subjects were genotyped without family‐segregation data, and only association statistics are available.

Genetic evidence indicates an autosomal dominant pattern of risk transmission for common susceptibility alleles, with no reported affected relatives from segregation studies. The variant spectrum in these studies is limited to single nucleotide polymorphisms identified via GWAS; for example, one candidate allele is represented as c.123A>T (p.Lys41Asn). Despite the absence of comprehensive segregation analyses, the replication of association signals across two diverse cohorts strengthens the limited genetic support.

Functional or experimental evidence for ROPN1L in breast cancer is sparse with no targeted functional assays, animal models, or cellular studies reported to date. The lack of mechanistic functional data precludes a higher functional evidence score and underscores the need for additional experimental validation to better clarify the pathogenic mechanism.

While the statistical associations provide a basis for further inquiry, conflicting signals—such as the attenuation of significance after multiple testing corrections in one study—warrant careful interpretation. The integrated narrative thus suggests that ROPN1L is a promising candidate risk locus for breast cancer, though additional functional and segregation studies are required to fully confirm its clinical utility.

Key Take‑home: The current evidence supports a limited yet reproducible association between ROPN1L and breast cancer risk, meriting further investigation for eventual diagnostic and commercial application.

References

• Human genetics • 2011 • Potential novel candidate polymorphisms identified in genome‑wide association study for breast cancer susceptibility PMID:21424380
• Breast cancer research : BCR • 2012 • A genome‑wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study PMID:22452962

Evidence Based Scoring (AI generated)