Characteristics of CRC patients
In our study, 1,003 CRC cases (431 colon cancer and 572 rectum cancer patients) and 1,303 normal controls were enrolled to investigate the correlation of the two SNPs (rs944289 and rs7990916) with the CRC risk. Table 1 listed detailed demographics data. The mean age of CRC patients and controls were 61.10 ±12.17 years and 61.40 ±9.61 years, respectively. There were no statistically significant differences in age and gender between the CRC patients and the controls (both P >0.05). However, smoking, alcohol intake and BMI increased the risk of CRC (both P <0.05), so we adjusted these factors by multiple logistic regression analyses.
Primary information for lncRNA rs944289 and rs7990916
The genotypic frequencies of lncRNA rs944289 and rs7990916 meet the HWE (P=0.105 and P=0.359, respectively). Minor allele frequency (MAF) of lncRNA rs944289 polymorphism was 0.28, which was similar to SNP database for Chinese populations (MAF=0.24). MAF of lncRNA rs7990916 polymorphism was 0.23, which was similar to SNP database for Chinese populations. Table 2 summarizes the corresponding information of lncRNA rs944289 and rs7990916.
Association of lncRNA polymorphisms with CRC risk in the overall population
The genotypes and allele distributions of lncRNA rs944289 and rs7990916 in the CRC patients and the controls were presented in Table 3. LncRNA rs944289 frequencies were 29.55% (CC), 46.73% (CT) and 23.72% (TT) in CRC patients, whereas in controls, the distributions of those genotypes were 29.69%, 51.62%, and 18.69%, respectively. We found that the rs944289 TT homozygote was associated with decreased CRC risk when compared with the CC or CC+CT (TT vs. CC: adjusted OR= 0.88, 95% CI: 0.78-0.99, P=0.037; TT vs. CC+CT: adjusted OR=0.86, 95% CI: 0.78-0.95, P=0.004). LncRNA rs7990916 frequencies were 79.69% (CC), 19.49% (CT) and 0.82% (TT) in CRC patients, and 77.31% (CC), 20.92% (CT) and 1.77% (TT) in controls. There was no significant difference between lncRNA rs7990916 and the susceptibility of CRC (all P >0.05).
Stratified analyses between lncRNA rs944289 polymorphism and CRC risk
Stratified analysis was performed and revealed that rs944289 TT genotype was associated with the decreased CRC risk in the subgroup of male (adjusted OR=0.88, 95% CI: 0.77-0.99, P=0.045), female (adjusted OR=0.81, 95% CI: 0.68-0.99, P=0.097), age≥61 (adjusted OR=0.86, 95% CI: 0.74-0.99, P=0.035), smoking (adjusted OR=0.66, 95% CI: 0.53-0.81, P<0.001), never alcohol intake (adjusted OR=0.88, 95% CI: 0.78-0.98, P=0.021) and BMI≥24 (adjusted OR=0.82, 95% CI: 0.696-0.94, P=0.0016) (Table 4).
Stratified analyses between lincRNA rs7990916 polymorphism and CRC risk
We further analyzed stratified effects of lncRNA rs7990916 on CRC risk by logistic regression model. Genotype distributions of rs7990916 were evaluated with age, sex, BMI, drinking and smoking. Results show that there was no significant association between the CRC patients and the control group except for age<61 (CT vs. CC: adjusted OR = 0.67, 95% CI: 0.48–0.93, P=0.018) (Table 5).
LncRNA rs944289/rs7990916 polymorphisms and CRC risk by site of tumor
Logistic regression analysis revealed that lncRNA rs944289 was associated with the increased risk of colon cancer (TT vs. CC+CT: adjusted OR=1.44, 95% CI: 1.11-1.88, P=0.007) or rectum cancer (TT vs. CC+CT: adjusted OR=1.29, 95% CI: 1.10-1.66, P=0.041) when compared with CC+CT (Table 6). We also found lncRNA rs7990916 did not alter the risk of colon cancer (CT vs. CC: adjusted P= 0.18, TT vs. CC: adjusted P= 0.21, CT+TT vs.CC: adjusted P=0.11, and TT vs. CC+CT: adjusted P= 0.24) or rectal cancer (CT vs. CC: adjusted P= 0.58, TT vs. CC: adjusted P=0.11, CT+TT vs. CC: adjusted P=0.37, and TT vs. CC+CT: adjusted P=0.12) (Table 6).