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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

RNASEL germline variants are associated with pancreatic cancer.

The RNASEL (encoding ribonuclease L) gene Glu265X mutation has been implicated in familial prostate cancer, and an association between the RNASEL Arg462Gln variant and sporadic and familial prostate cancer, has also been suggested. Because prostate cancer occurs in some familial pancreatic cancer families, we evaluated the role of the RNASEL gene variants Glu265X and Arg462Gln in the etiology of pancreatic cancer. Exon 2 of the RNASEL gene was directly sequenced in the germline of 36 familial and 75 sporadic pancreatic cancer patients and in 108 controls. The Glu265X mutation was identified in one (2.8%) familial and one (1.3%) sporadic pancreatic cancer case, but not in any of the controls. Arg462Gln variants were identified in 61 (56%) controls and in 55 (73%) sporadic pancreatic cancer cases with 8 (7%) and 12 (16%) homozygotes, respectively (p = 0.009). For homozygous carriers the increased risk for pancreatic cancer was 3.5 (odds ratio [OR] = 3.53, 95% confidence interval [CI] = 1.11-11.46, p = 0.03). The population attributable fraction (PAF) was 38.7% (95% CI = 0.08-0.80). In familial pancreatic cancer no association between Arg462Gln genotypes and pancreatic cancer risk was evident. In sporadic pancreatic cancer there were no significant differences between Arg462Gln genotypes regarding clinical characteristics. In familial pancreatic cancer, however, patients with Arg462Gln variants had more aggressive tumors with more high grade cancers (OR = 15.40, p = 0.009) and more distant metastases (OR = 7.00, p = 0.04) than patients with the wild-type genotype. Our results suggest that RNASEL variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer, which has to be proven in large scale studies.[1]


  1. RNASEL germline variants are associated with pancreatic cancer. Bartsch, D.K., Fendrich, V., Slater, E.P., Sina-Frey, M., Rieder, H., Greenhalf, W., Chaloupka, B., Hahn, S.A., Neoptolemos, J.P., Kress, R. Int. J. Cancer (2005) [Pubmed]
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