AbstractBackgroundRecently, ADCY9 has been found to be highly expressed in colon cancer, and high ADCY9 expressionis a poor prognostic factor of colon cancer. However, no study has reported on the relationship between single nucleotide polymorphisms (SNPs) of ADCY9 and colorectal cancer risk in the Chinese Han population.MethodsTo evaluate the association between four ADCY9 SNPs and colorectal cancer risk, we performed a case–control study including 511 colorectal cancer patients and 511 healthy controls. SNPs were genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). The distributions of alleles and genotypes frequencies between the case and control groups were compared using chi‐squared. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender to assess the association between SNPs and colorectal cancer risk.ResultsThe overall analysis found that rs2230742 was associated with an increased risk of colorectal cancer (AA versus GG: OR = 3.54, 95% CI = 1.16–10.86, p = 0.027; recessive model: OR = 3.55, 95% CI = 1.16–10.85, p = 0.027). Stratification analysis showed that rs2230742 was associated with an increased rectal cancer risk; rs11076810 was associated with a reduced colorectal cancer risk for age > 59 years. No association was observed between other two SNPs and colorectal cancer risk.ConclusionsOur findings suggest that ADCY9 polymorphisms (rs2230742 and rs11076810) have an effect on colorectal cancer risk in the Chinese Han population. Future association and functional studies are required to confirm our findings and explore the mechanism of ADCY2 in colorectal cancer.