Colorectal cancer

Numerous SNPs have been reported to be associated with increased risk of developing colorectal cancer (CRC), including:

• The 3 SNPs that form the basis for gs298, a genoset predicting a possible benefit to increased CRC screening for individuals with that genoset;
• rs6983267 in the 8q24 region [PMID 20648012]
• rs2273535 in the AURKA gene
• rs7903146, originally associated with risk for type 2 diabetes
• rs4779584 in ch 15q13.3 [PMID 20648012]
• rs6983267
• rs4939827 in ch 18q21.1 [PMID 20648012]
• rs2273535
• rs1047972
• rs719725 in ch 9p24
• rs10505477
• rs36053993 in the MUTYH gene
• Three SNPs in the SMAD7 gene, found in a large (>7,000 cases) study [PMID 17934461]:
  • rs4939827
  • rs12953717
  • rs4464148

Some of the SNPs listed above were also associated with colorectal cancer in a study of ~1800 Swedish patients. [PMID 20648012] This same study confirmed association for the following SNPs:

• rs16892766 in the 8q23.3 chromosomal region
• rs10795668 in ch 10p14
• rs3802842 in ch 11q23.1
• rs9929218 in ch 16q22.1
• rs10411210 in ch 19q13.1
• rs961253 in ch 20p12.3

Some SNPs appear to lower the risk of developing colorectal cancer and also to lower the risk of its metastasis:

• rs2306536 in the CHFR gene
• rs1049174, representing a haplotype of the KLRK1 gene
• rs1864010 in the INSR gene
• rs1801278 in the IRS1 gene

Other SNPs have been associated with the efficacy of various treatments for CRC:

• Colorectal cancer patients being treated with the chemotherapeutic drug irinotecan are the subject of an FDA approved genetic test designed to assess a SNP in the UGT1A1 gene. Drug dosage guidelines are different for different rs34815109 genotypes.
• rs396991 influences progression-free survival when using cetuximab to treat metastatic CRC
• nejm K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer

2009 Review: Pharmacogenetics and biomarkers in colorectal cancer.[PMID 19381163]

[PMID 17914568] The Gln/Gln genotype at codon 302 in RAD18 was significantly more frequent in CRC (18.0%) than in the healthy controls (11.5%) (p=0.046). The increased risk was detected in CRC patients with the Gln/Gln genotype (Odds ratio [OR], 2.10; 95% confidence interval [CI], 1.00 to 4.40). When the relationship of the SNP with clinicopathological parameters of CRC was investigated, particularly in the well-differentiated grade and in the lymph node metastasis (N1) CRC patients, significantly higher risks were detected (OR, 7.00; 95% CI, 1.19-41.1 and OR, 3.71; 95% CI, 1.30-10.6, respectively).