Mutations in IGF Pathway Genes Associated With Prostate Cancer Mortality

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In a study reported in the Journal of the National Cancer Institute, Cao and colleagues identified mutations in insulin-like growth factor (IGF) pathway genes that were significantly associated with mortality in prostate cancer.

Analysis of 530 single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes in 5,887 European-ancestry prostate cancer patients, including 704 who died from the disease, showed that mutations in the IGF signaling pathway overall were significantly associated with prostate cancer mortality (P = .03), with mutation in IGF2-AS and SSTR2 being the main contributors to the association (both P = .04).

In SNP-specific analysis, 36 SNPs were associated with prostate cancer mortality (P < .05 for trend). However, only three SNPs in IGF2-AS remained significant after gene-based corrections; two were in linkage disequilibrium (rs1004446 and rs3741211) and one (rs4366464) was independent.

The hazard ratios per each additional risk allele were 1.19 (P = .003 for trend) for rs3741211 and 1.44 (P < .001 for trend) for rs4366464, with the effect of rs4366464 remaining significant after correction for all SNPs (P = .04 for trend). In 2,424 patients, including 313 who died, prediagnostic circulating IGF1 and IGFBP3 levels were not significantly associated with mortality.

The investigators concluded, “The IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in [prostate cancer] survival.” ■

Cao Y, et al: J Natl Cancer Inst 106:dju085, 2014