Genetic variations are associated with lymph node metastasis in colorectal cancer patients

Background and Objectives: Regional lymph nodes (LNs) are believed to be a first-line barrier against tumor metastasis. However, it remains unclear whether underlying genetic factors exist and affect LN metastasis risk. We therefore evaluated inherited risk variants using single nucleotide polymorphisms (SNPs) in pathological T3 colorectal cancer patients in the absence or presence of LN metastasis. Methods: The study population comprised 629 retrospectively collected colorectal cancer samples between 2000 and 2009 in a single hospital, including 273 patients with LN metastasis and 355 control subjects without LN metastasis. We analyzed 87 SNPs in genes that are associated with susceptibility to carcinogenesis or metastasis in colorectal or other cancers. Results: Only 11 SNPs were found to have significant genotype distribution differences between the cases and controls. The average number of risk alleles carried by patients with LN metastasis was 7 (6.6 ± 1.4; range 2-10), which was significantly higher than the 6 risk alleles that were carried on average by patients without LN metastasis (6.0 ± 1.6; range 0-10; P < 0.001). Conclusions: Certain SNPs can increase genetic susceptibility to LN metastasis. As the number of risk alleles increases, the risk of LN metastasis also increases, although the difference is subtle.