Table 3.
Top 5 SNPS for which interaction between calcium intake and that specific genetic variant in relation to CRC outcomes was observed.
| MULTIPLICATIVE INTERACTIONS | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Interaction GxE (calcium and CaSR) | |||||||||||
| All-cause mortality | CRC-specific mortality | ||||||||||
| Dietary calcium sex- and cohort- specific quartiles | Dietary calcium sex- and cohort- specific quartiles | ||||||||||
| SNP | N/events | RERIa | 95%CI | P-valueb | MAF | SNP | N/events | RERIa | 95%CI | P-valueb | MAF |
| 3:121910706_A/G rs1553309 | 11173/3841 | 1.04 | 1.00–1.08 | 0.075 | 0.42 | 3:121903842_C/A rs6780443d | 11173/2499 | 1.08 | 1.02–1.14 | 0.012 | 0.24 |
| 3:121914667_T/C rs6764205c | 11173/3841 | 1.04 | 1.00–1.09 | 0.049 | 0.30 | 3:121909830_C/G rs17282008d | 11173/2499 | 1.07 | 1.01–1.14 | 0.018 | 0.24 |
| 3:121921700_T/C rs46780431219c | 11173/3841 | 1.05 | 1.00–1.09 | 0.048 | 0.30 | 3:121932422_C/T rs62269066e | 11173/2499 | 1.06 | 1.00–1.11 | 0.038 | 0.36 |
| 3:121922863_A/G rs4678045c | 11173/3841 | 1.05 | 1.00–1.09 | 0.048 | 0.30 | 3:121936453_G/A rs11713280 | 11173/2499 | 1.12 | 1.01–1.23 | 0.026 | 0.07 |
| 3:121936453_G/A rs11713280 | 11173/3841 | 1.09 | 1.01–1.18 | 0.023 | 0.07 | 3:121966952_C/T rs7637874d | 11173/2499 | 1.07 | 1.01–1.13 | 0.031 | 0.24 |
| Supplement ≥ 1 versus < 1 pill | Supplement ≥ 1 versus < 1 pill | ||||||||||
| 3:121913708_C/T rs17282015e | 9207/3210 | 1.24 | 1.09–1.42 | 0.0009 | 0.36 | 3:121913708_C/T rs17282015e | 9207/1999 | 1.25 | 1.07–1.47 | 0.006 | 0.36 |
| 3:121917298_T/C rs11708053e | 9207/3210 | 1.25 | 1.10–1.42 | 0.0007 | 0.36 | 3:121917298_T/C rs11708053e | 9207/1999 | 1.26 | 1.07–1.47 | 0.005 | 0.36 |
| 3:121917387_A/G rs11711698e | 9207/3210 | 1.25 | 1.10–1.42 | 0.0007 | 0.36 | 3:121917387_A/G rs11711698e | 9207/1999 | 1.25 | 1.07–1.47 | 0.005 | 0.36 |
| 3:121932422_C/T rs62269066e | 9207/3210 | 1.25 | 1.10–1.43 | 0.0006 | 0.36 | 3:121932422_C/T rs62269066e | 9207/1999 | 1.24 | 1.06–1.46 | 0.008 | 0.36 |
| 3:121936453_G/A rs11713280 | 9207/3210 | 1.49 | 1.19–1.87 | 0.0006 | 0.07 | 3:121936453_G/A rs11713280 | 9207/1999 | 1.6 | 1.21–2.11 | 0.0009 | 0.07 |
| Total calcium intake sex- and cohort- specific quartiles | Total calcium intake sex- and cohort- specific quartiles | ||||||||||
| 3:121992825_C/T rs3804594f | 4646/1695 | 0.87 | 0.78–0.97 | 0.011 | 0.08 | 3:121994941_G/A rs2279802f | 4646/1005 | 0.81 | 0.70–0.94 | 0.005 | 0.08 |
| 3:121995415_C/T rs13093602f | 4646/1695 | 0.87 | 0.78–0.97 | 0.013 | 0.08 | 3:121995415_C/T rs13093602f | 4646/1005 | 0.81 | 0.70–0.94 | 0.005 | 0.08 |
| 3:121996810_T/A rs1827381f | 4646/1695 | 0.87 | 0.78–0.97 | 0.013 | 0.08 | 3:121996810_T/A rs1827381f | 4646/1005 | 0.81 | 0.70–0.94 | 0.005 | 0.08 |
| 3:121997268_T/C rs3792291f | 4646/1695 | 0.87 | 0.78–0.97 | 0.013 | 0.08 | 3:121997268_T/C rs3792291f | 4646/1005 | 0.81 | 0.70–0.94 | 0.005 | 0.08 |
| 3:121999059_G/A rs2055427f | 4646/1695 | 0.87 | 0.78–0.97 | 0.012 | 0.08 | 3:121999059_G/A rs2055427f | 4646/1005 | 0.81 | 0.70–0.94 | 0.005 | 0.08 |
| ADDITIVE INTERACTIONS | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dietary calcium sex- and cohort- specific quartiles | Dietary calcium sex- and cohort- specific quartiles | ||||||||||
| 3:121921700_T/C rs4678043c | 11173/3841 | 0.04 | −0.00–0.08 | 0.068 | 0.30 | 3:121903842_C/A rs6780443d | 11173/2499 | 0.06 | 0.02–0.11 | 0.013 | 0.24 |
| 3:121922863_A/G rs4678045c | 11173/3841 | 0.04 | −0.00–0.09 | 0.070 | 0.30 | 3:121909830_C/G rs17282008d | 11173/2499 | 0.06 | 0.01–0.11 | 0.018 | 0.24 |
| 3:121936453_G/A rs11713280 | 11173/3841 | 0.07 | 0.02–0.13 | 0.015 | 0.07 | 3:121936453_G/A rs11713280 | 11173/2499 | 0.09 | 0.03–0.15 | 0.012 | 0.07 |
| 3:121996235_G/A rs77663377 | 11173/3841 | 0.07 | −0.01–0.14 | 0.080 | 0.15 | 3:121966952_C/T rs7637874d | 11173/2499 | 0.06 | 0.01–0.10 | 0.037 | 0.24 |
| 3:122005273_A/G rs34042920 | 11173/3841 | 0.04 | −0.01–0.10 | 0.107 | 0.10 | 3:121996235_G/A rs77663377 | 11173/2499 | 0.09 | 0.003–0.17 | 0.051 | 0.15 |
| Supplement ≥ 1 versus < 1 pill | Supplement ≥ 1 versus < 1 pill | ||||||||||
| 3:121903842_C/A rs6780443d | 9207/3210 | 0.22 | 0.09–0.36 | 0.0009 | 0.24 | 3:121903842_C/A rs6780443d | 9207/1999 | 0.23 | 0.05–0.41 | 0.010 | 0.24 |
| 3:121909830_C/G rs17282008d | 9207/3210 | 0.22 | 0.09–0.36 | 0.0009 | 0.24 | 3:121909830_C/G rs17282008d | 9207/1999 | 0.23 | 0.05–0.41 | 0.009 | 0.24 |
| 3:121932422_C/T rs62269066e | 9207/3210 | 0.21 | 0.10–0.32 | 0.00006 | 0.36 | 3:121917298_T/C rs11708053e | 9207/1999 | 0.22 | 0.07–0.36 | 0.003 | 0.36 |
| 3:121936453_G/A rs11713280 | 9207/3210 | 0.40 | 0.15–0.64 | 0.0009 | 0.07 | 3:121936453_G/A rs11713280 | 9207/1999 | 0.51 | 0.18–0.84 | 0.002 | 0.07 |
| 3:121966952_C/T rs7637874d | 9207/3210 | 0.22 | 0.08–0.36 | 0.0009 | 0.24 | 3:121966952_C/T rs76377874d | 9207/1999 | 0.22 | 0.04–0.09 | 0.015 | 0.24 |
| Total calcium intake sex- and cohort- specific quartiles | Total calcium intake sex- and cohort- specific quartiles | ||||||||||
| 3:121984792_G/A rs17197671g | 4646/1695 | 0.07 | 0.004–0.13 | 0.015 | 0.14 | 3:121930454_C/G rs75473459h | 4646/1005 | 0.10 | 0.02–0.18 | 0.021 | 0.11 |
| 3:121988851_G/C rs6783855g | 4646/1695 | 0.07 | 0.004–0.13 | 0.015 | 0.14 | 3:121917298_T/C rs11708053e | 4646/1005 | 0.08 | 0.01–0.15 | 0.030 | 0.36 |
| 3:121990800_T/C rs1604446g | 4646/1695 | 0.07 | 0.004–0.13 | 0.015 | 0.14 | 3:121917387_A/G rs11711698e | 4646/1005 | 0.08 | 0.01–0.15 | 0.032 | 0.36 |
| 3:122002178_T/C rs2134224g | 4646/1695 | 0.07 | 0.003–0.13 | 0.014 | 0.14 | 3:121939743_C/T rs36004543h | 4646/1005 | 0.11 | 0.03–0.19 | 0.004 | 0.12 |
| 3:122005273_A/G rs34042920g | 4646/1695 | 0.09 | 0.03–0.16 | 0.005 | 0.10 | 3:121958475_G/A rs62269089h | 4646/1005 | 0.10 | 0.01–0.18 | 0.020 | 0.11 |
aModels were adjusted for age at diagnosis, sex, cohort, and the first three principal components of genetic ancestry as well as main effects of calcium intake (dietary, supplemental or total) and SNPs. Sex- and cohort- specific quartiles as well as SNPs were entered as continuous variables for both the multiplicative as the additive interaction models.
bThe estimated effective number of independent tests among 325 SNPS was 35 based on the simple M approach. Therefore, p < 0.001 were considered statistically significant (n = 35; 0.05/35 = 0.001).
c,d,e,f,g,hCorrelated SNPS (r2 > 0.6).