RCCD1 – Exocrine Pancreatic Carcinoma

The association between RCCD1 and exocrine pancreatic carcinoma is supported by robust data from two large transcriptome‑wide association studies. These investigations, conducted in European populations, leveraged genetically predicted expression in normal pancreatic tissue to implicate RCCD1 in cancer risk. The cohorts comprised thousands of cases and controls, providing a statistically significant association (PMID:32907841) (PMID:31917448). Such scale and replication across independent studies enhance the clinical confidence in the observed relationship. The overall strength of the evidence has been rated as Strong based on extensive sample sizes and reproducibility of findings. This robust association supports further diagnostic evaluation and potential translational research.

The ClinGen gene‑disease association for RCCD1 in exocrine pancreatic carcinoma is classified as Strong. While the individual studies did not report classical case‑level variant segregation, the analyses integrated large numbers of probands derived from genome‑wide data from over 8,000 cancer cases. This convergence of data from independent cohorts underpins the assignment of a strong category, reflecting both statistical significance and reproducibility across studies (PMID:32907841) (PMID:31917448).

Genetic evidence is derived primarily from associations of predicted gene expression with risk rather than direct genotype–phenotype correlations. No individual RCCD1 coding variants or specific mutational events meeting the HGVS criteria were reported within the provided data. Consequently, the genetic evidence remains limited to transcriptional association data without the complement of classical segregation or variant spectrum analysis. This has led to a ClinGen genetic evidence rating of Limited, emphasizing the need for further variant‐level studies.

The available data do not offer additional segregation information since familial studies or the assessment of affected relatives were not reported. Thus, no extra segregation details are available beyond the aggregated association data, which precludes boosting the genetic evidence score through family‐based analyses. Inheritance in this context remains complex and does not conform to classical Mendelian patterns. This is typical of many cancer susceptibility associations that emerge from population‐based studies rather than high‑penetrance familial variants.

Functional or experimental evidence specifically addressing RCCD1 in the context of exocrine pancreatic carcinoma is currently lacking. There are no reported in vitro or in vivo studies, cellular models, or rescue experiments to elucidate the mechanistic role of RCCD1. As such, the functional evidence is rated as Limited. The absence of direct functional validation highlights an opportunity for future research to determine the biological mechanisms underpinning the observed association.

In summary, the integration of large‑scale transcriptome‑wide association data provides strong evidence for the involvement of RCCD1 in exocrine pancreatic carcinoma risk. Although the genetic evidence is limited to expression associations and functional data are not available, the consistency and scale of the epidemiological findings support the clinical utility of RCCD1 as a candidate susceptibility gene. This evidence informs diagnostic decision‑making and highlights RCCD1 as a promising target for further functional and clinical research.

References

• Cancer Research • 2020 • A Transcriptome-Wide Association Study Identifies Candidate Susceptibility Genes for Pancreatic Cancer Risk PMID:32907841
• Journal of the National Cancer Institute • 2020 • A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer PMID:31917448

Evidence Based Scoring (AI generated)