A let-7 microRNA-complementary site (LCS6) polymorphism in the 3’UTR of KRAS has been shown to disrupt let-7 binding and upregulate KRAS expression. As reported in Clinical Cancer Research, Sha and colleagues found that LCS6 genotype was not associated with KRAS mutation status or disease-free survival in patients with stage III colon cancer enrolled in a phase III trial (NCCTG N0147).
The LCS6 genotype was assayed by real-time polymerase chain reaction in DNA from whole blood (n = 2,834) and compared to paired tumor tissue (n = 977). A total of 432 blood samples (15.2%) and 143 tumor samples (14.6%) were heterozygous or homozygous for the LCS6 G-allele, and 2402 blood samples (84.8%) and 834 tumor samples (85.4%) were homozygous for the LCS6 T-allele.
Genotype results were highly concordant (99.8%) in 977 cases with paired blood and tumor tissue. G-allele carriers were significantly more frequent in Caucasians vs other races (P < .0001). The LCS6 genotype was not significantly associated with KRAS mutation status, clinicopathologic features (all P > .2), or disease-free survival (hazard ratio = 0.929, P = .49). Results were unchanged in analysis combining LCS6 genotype and KRAS mutation status.
The investigators concluded, “In the largest association study investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors.” ■
Sha D, et al: Clin Cancer Res. April 11, 2014 (early release online).
