JAG1 polymorphism is associated with incident neoplasm in a southern Chinese population

AIM: Jagged 1 (JAG1) is a ligand of notch receptors that regulates cell division, differentiation, and survival. Over‐expression of JAG1 has been linked to increased risk of cancer. We previously showed that rs2273061 of JAG1 was associated with bone mineral density (BMD) using genome‐wide association, and the SNP was associated with JAG1 expression in bone and blood cells. We hypothesized that this SNP has association with neoplasm. METHODS: The SNP rs2273061 of JAG1 was genotyped in two independent cohorts without history of neoplasm at baseline. The cohorts were followed (median 10.8 years) for development of neoplasm using electronic medical database of the Hong Kong Hospital Authority. Ascertainment of neoplasm was based on ICD9 code 140‐239. Cox proportional hazards regression models adjusted for age, sex, BMI, and lumbar spine BMD Zscore were used for association analysis. AUC was used to test predictive accuracy of the models. RESULT: In the first cohort (n=731; 80 incidents; 7620 person‐year), minor allele (G) of rs2273061 was significantly associated with neoplasm (HR=0.68; 95%CI:0.47‐0.98). The result was validated (HR=0.81; 95% CI:0.66‐0.99) in replication cohort (n=1,885; 241 incidents; 19966 person‐year). Meta‐analysis showed a more significant association (HR=0.78; 95% CI:0.65‐0.93; p=0.005). AUC for basic clinical model (age+sex+BMI) in predicting neoplasm was 0.618 (95%CI: 0.588‐0.648). The addition of rs2273061 genotype to the basic model increased AUC to 0.635 (95%CI: 0.605‐0.665), and the increment was statistically significant. Conclusion: JAG1 polymorphism has association with incident neoplasm However, further study is required to evaluate any functional effects of rs2273061 on tumor formation.