Genome-Wide Identification of Chemosensitive SNP Markers in Colorectal Cancers

Scientists in Seoul, Korea, have made significant strides in understanding the genetic factors influencing chemotherapy response in colorectal cancer patients. A groundbreaking report published in Cancer Science outlines a novel three-step process for identifying single nucleotide polymorphism (SNP) markers that predict chemoresponsiveness. This breakthrough has the potential to revolutionize cancer treatment by tailoring therapies to individual patients' genetic profiles.

Key Takeaways:

• The researchers conducted a genome-wide screening of chemosensitive SNPs in association with in vitro chemosensitivity assays in 104 colorectal cancer patients.
• The study identified 12 SNPs associated with six regimens, including fluoropyrimidine-based adjuvant chemotherapy, which correlated with tumor recurrence and shorter disease-free survival.
• The substitution alleles of GPC5 rs553717 (AA) were found to be significantly associated with tumor recurrence and shorter disease-free survival in patients receiving fluoropyrimidine-based adjuvant chemotherapy.
• The study also identified RKO cells expressing mutant GPC5, which showed enhanced cell death in response to 5-FU in cytotoxicity assays.
• The candidate chemosensitive SNP markers identified in the study, including those identified in vitro, can now be further verified in a large cohort study.
• The researchers used a three-step process consisting of in vitro screening, identification, and validation to identify chemosensitive SNP markers.

Statistics:

• 104 colorectal cancer patients were used for the initial screening step.
• 260 evaluable patients were used for clinical association analysis in the validation step.
• 12 SNPs were initially chosen during the screening and identifying steps.
• The substitution alleles of GPC5 rs553717 (AA) correlated significantly with tumor recurrence and shorter disease-free survival in patients receiving fluoropyrimidine-based adjuvant chemotherapy (p=0.019 and 0.023, respectively).
• Patients that were homozygous for the reference alleles SSTR4 rs2567608 (AA) and EPHA7 rs2278107 (TT) showed lower disease control rates in response to irinotecan and oxaliplatin regimens, respectively, than those with substitution alleles (p=0.022 and 0.014, respectively).

Sources:

• Kim, J.C., et al. (2010). Genome-wide identification of chemosensitive single nucleotide polymorphism markers in colorectal cancers. Cancer Science, 101(4), 1007-13.
• University of Ulsan, Department of Surgery
• Cancer Science publication: Volume 101, Issue 4, 2010.