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Association study of the let-7 miRNA-complementary site variant in the 3 ' untranslated region of the KRAS gene in stage III colon cancer ( NCCTG N0147 Clinical Trial ) . PURPOSE A let-7 microRNA-complementary site ( LCS6 ) polymorphism in the 3 ' untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression . We evaluated the LCS6 genotype and its association with KRAS mutation status , clinicopathologic features , and disease-free survival ( DFS ) in patients with stage III colon cancer who enrolled in a phase III clinical trial ( NCCTG N0147 ) . EXPERIMENTAL DESIGN The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood ( n = 2,834 ) and compared with paired tumor tissue ( n = 977 ) . χ ( 2 ) and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status . Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS , respectively . RESULTS We identified 432 ( 15.2 % ) blood samples and 143 ( 14.6 % ) tumor samples heterozygous or homozygous for the LCS6 G-allele , and 2,402 of 2,834 ( 84.8 % ) blood samples and 834 of 977 ( 85.4 % ) tumor samples homozygous for the LCS6 T-allele . Genotype results were highly concordant ( 99.8 % ) in cases with paired blood and tumor tissue ( n = 977 ) . G-allele carriers were significantly more frequent in Caucasians versus other races ( χ ( 2 ) test , P < 0.0001 ) . The LCS6 genotype was not associated with KRAS mutation status , clinicopathologic features ( all P > 0.2 ) , or DFS ( log-rank P = 0.49 ; HR , 0.929 ; 95 % confidence interval , 0.76-1.14 ) , even after combining LCS6 genotype with KRAS mutation status . CONCLUSIONS 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 .
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Intervention_Control
real-time PCR in DNA extracted from whole blood ( n = 2,834 )
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Intervention_Control
compared with paired tumor tissue
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Outcome_Physical
KRAS mutation status , clinicopathologic features
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Outcome_Mortality
disease-free survival ( DFS )
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Participant_Condition
stage III colon cancer ( NCCTG N0147 Clinical Trial ) .
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Participant_Condition
patients with stage III colon cancer who enrolled in a phase III clinical trial ( NCCTG N0147 ) .
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Participant_Condition
patients defined by LCS6 variant status
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Participant_Condition
in Caucasians versus other races
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Participant_Condition
patients with stage III tumors