Royal Marsden Hospital, London & Sutton, United Kingdom
Elizabeth Catherine Smyth , Kyriakos Kouvelakis , David Cunningham , Clare Peckitt , Matthew Guy Nankivell , William H. Allum , Andrew Wotherspoon , Jens Hahne , Andrea Lampis , Ruth E. Langley , Nicola Valeri
Background: Single nucleotide polymorphisms (SNPs) in mir-608 (rs4919510) are prognostic in colorectal cancer (CRC) and hepatocellular cancer. SNPs of the let-7 complementary site 6 (LCS-6) 3'-untranslated region of KRAS (rs61764370) are associated with prognosis in CRC and platinum sensitivity in head and neck cancer. We investigated the prognostic effects of these SNPs in patients treated with surgery and with perioperative epirubicin, cisplatin and 5-fluorouracil chemotherapy plus surgery in the MRC MAGIC trial. Methods: DNA was extracted from tumour tissue using the QIAamp DNA FFPE Tissue Kit (Qiagen, Hilden, Germany). Samples were genotyped using the Taqman assay (Life Technologies, Carlsbad, CA) for rs4919510 in mir-608 and rs61764370 in LCS-6. SNP status was assessed for association with patient characteristics and survival. Results: 305 patients (of 456 operated) had mir-608 and/or LCS-6 results available. SNPs mir-608 and LCS-6 were in Hardy-Weinberg equilibrium. Pathological tumour regression grading was not different for any SNP genotype. No genotype was statistically significantly associated with overall survival in either surgery arm or chemotherapy plus surgery arm of the trial (Table). Conclusions: Germline polymorphisms in mir-608 and LCS-6 showed no evidence of a prognostic effect in patients with gastric and gastroesophageal cancer treated with surgery or chemotherapy plus surgery in the MAGIC trial. However, the small number of patients with selected genotypes means that these analyses may be underpowered to detect survival differences.
Chemotherapy+Surgery arm | |||||||
---|---|---|---|---|---|---|---|
N | Events | Median OS | 95% CI OS | HR | 95% CI HR | P | |
mir-608 | |||||||
CC | 95 | 59 | 20.5 | 12.6-35.2 | Ref | ||
CG | 38 | 26 | 22.3 | 13.0-53.6 | 0.99 | 0.62-1.57 | |
GG | 5 | 3 | 79.8 | 17.3-NA | 0.56 | 0.17-1.79 | 0.62 |
LCS-6 | |||||||
GG | 2 | 2 | 5.8 | 5.8-NA | Ref | ||
TG | 21 | 14 | 21.9 | 8.1-34.4 | 0.41 | 0.09-1.81 | |
TT | 115 | 72 | 22.5 | 15.6-43.0 | 0.35 | 0.09-1.44 | 0.32 |
Surgery arm | |||||||
mir-608 | |||||||
CC | 100 | 69 | 19.2 | 14.1-27.2 | Ref | ||
CG | 58 | 32 | 34.0 | 19.5-52.5 | 0.71 | 0.47-1.08 | |
GG | 9 | 8 | 17.7 | 0.2-42.8 | 1.34 | 0.64-2.79 | 0.15 |
LCS-6 | |||||||
GG | 3 | 2 | 22.1 | 22.1-NA | Ref | ||
TG | 20 | 12 | 19.5 | 5.5-NA | 0.95 | 0.21-4.27 | |
TT | 143 | 95 | 20.3 | 16.4-28.8 | 1.14 | 0.28-4.66 | 0.83 |
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