Association between ICOS polymorphisms and risk of colorectal cancer: a case-control study involving 2,606 subjects

Functional variants in inducible T cell costimulator (ICOS) gene are predicted to be associated with the susceptibility of colorectal cancer (CRC). In this study, we enrolled 2,606 participants (involving 1,003 CRC cases and 1,303 healthy controls) and conducted a case-control study to explore the potential relationship of ICOS rs4404254 T>C and rs10932029 T>C polymorphisms with the risk of CRC. A custom-by-design 48-Plex SNPscan Kit was used to obtain the genotypes of ICOS rs4404254 T>C and rs10932029 T>C variants. We found that ICOS rs10932029 T>C polymorphism was associated with risk of CRC in several subgroups (female subgroup: CC vs. TT: adjusted OR = 6.49, 95% CI 1.36-30.90, P = 0.019 and CC vs. CT/TT: adjusted OR = 6.38, 95% CI 1.34-30.32, P = 0.020; < 61 years subgroup: CC vs. TT: adjusted OR = 4.23, 95% CI 1.10-16.24, P = 0.036 and CC vs. CT/TT: adjusted OR = 4.20, 95% CI 1.10-16.09, P = 0.036; never smoking subgroup: CC vs. TT: adjusted OR = 2.82, 95% CI 1.04-7.64, P = 0.041 and CC vs. CT/TT: adjusted OR = 2.83, 95% CI 1.05-7.66, P = 0.041 and BMI ≥ 24 subgroup: CC vs. TT: adjusted OR = 6.81, 95% CI 1.39-33.30, P = 0.018 and CC vs. CT/TT: adjusted OR = 6.79, 95% CI 1.39-33.11, P = 0.018). In addition, we found that ICOS rs4404254 T>C polymorphism was associated with the susceptibility of CRC in never smoking subgroup (CC/TC vs. TT: adjusted OR = 1.23, 95% CI 1.01-1.51, P = 0.045). In summary, our findings suggest that ICOS rs10932029 T>C and ICOS rs4404254 T>C polymorphisms may be associated with the risk of CRC. In the future, a fine-mapping study with a functional evaluation is needed to explore the relationship between ICOS polymorphisms and the risk of CRC.