Table 1.
Characteristics of IR SNPs and their effect on IR and CRC risk.
| Gene | SNP | Chr | Position | Allele | Alternative allele frequency | IR | CRC risk | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ref/Alt | Controls | CRC | OR | P | Q | HR£ (95% CI) | P | ||||
| (n = 10,342) | (n = 736) | ||||||||||
| Fasting glucose | |||||||||||
| G6PC2* | rs13431652 | 2 | 169,753,415 | T/C | 0.30 | 0.32 | 0.79 | 6.99E-09 | 0.706 | 1.07 (0.96–1.19) | 0.244 |
| G6PC2§ | rs560887 | 2 | 169,763,148 | T/C | 0.29 | 0.32 | 1.28 | 6.12E-09 | 0.513 | 0.88 (0.78–0.99) | 0.027 |
| MKLN1† | rs117911989 | 7 | 130,969,793 | G/A | 0.05 | 0.03 | 1.98 | 3.97E-08 | 0.209 | 0.56 (0.34–0.91) | 0.020 |
| NKX2-2† | rs7273292 | 20 | 21,473,362 | T/C | 0.01 | 0.0001 | 3.37 | 4.35E-08 | 0.148 | 1.09 (0.54–2.18) | 0.813 |
| Fasting insulin | |||||||||||
| NR5A2¶ | rs10919774 | 1 | 199,907,716 | G/A | 0.95 | 0.95 | 1.98 | 2.53E-08 | 0.726 | 0.87 (0.57–1.34) | 0.531 |
| MTRR/LOC729506€ | rs722025 | 5 | 8,108,012 | G/A | 0.75 | 0.73 | 1.28 | 3.73E-08 | 0.643 | 0.59 (0.40–0.89) | 0.011 |
| PLA2G4A¥ | rs6683451 | 1 | 187,292,608 | A/C | 0.11 | 0.09 | 3.16 | 4.86E-08 | 0.230 | 1.88 (0.24–14.95) | 0.552 |
| HOMA-IR | |||||||||||
| PABPC1P2* | rs77772624 | 2 | 147,499,474 | A/C | 0.001 | 0.001 | 29.65 | 4.96E-09 | 0.634 | 1.01 (0.25–4.09) | 0.987 |
| PABPC1P2§ | rs77772624 | 2 | 147,499,474 | A/C | 0.001 | 0.001 | 28.92 | 9.36E-09 | 0.711 | 0.54 (0.08–3.84) | 0.535 |
| MSC¥ | rs13277245 | 8 | 72,606,942 | A/G | 0.18 | 0.18 | 29.57 | 4.92E-08 | N/A | 1.37 (0.83–2.27) | 0.224 |
| DOCK1¥ | rs113847670 | 10 | 128,874,679 | C/T | 0.04 | 0.03 | 9.18 | 2.85E-08 | 0.571 | 0.41 (0.11–1.60) | 0.201 |
| LINC00460* | rs17254590 | 13 | 107,037,344 | G/C | 0.02 | 0.0004 | 2.52 | 2.40E-08 | 0.620 | 0.64 (0.09–4.69) | 0.661 |
| LINC00460§ | rs17254590 | 13 | 107,037,344 | G/C | 0.02 | 0.0004 | 2.67 | 8.86E-09 | 0.882 | 0.66 (0.09–4.87) | 0.685 |
Alt, alternative allele; Chr, chromosome; CI, confidence interval; CRC, colorectal cancer; HOMA-IR, homeostatic model assessment–insulin resistance; HR, hazard ratio; IR, insulin resistance; N/A, not available; OR, odds ratio; Q, Cochran's Q; Ref, reference allele; SNP, single–nucleotide polymorphism. Numbers in bold face are statistically significant.
£ HR was estimated by adjusting for confounding factors (10 genetic principal components plus age, education, family income, depressive symptoms, cardiovascular disease ever, hypertension ever, high cholesterol, family history of CRC, physical activity, smoking, height, body mass index, waist-to-hip ratio, dietary alcohol, dietary fiber, daily fruits, daily vegetables, % calories from saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and protein, hysterectomy ever, ages at menarche and at menopause, breastfeeding, oral contraceptive duration, and exogenous estrogen [E]-only, and E plus progestin use).
SNPs at genome-wide level identified in the overall analysis.
SNPs at genome-wide level in subgroup analysis within the high-fat diet group (≥7.0% calories from saturated fatty acids [SFA]).
SNPs at genome-wide level in subgroup analysis within the physically active group (≥10 metabolic equivalent [MET]).
SNPs at genome-wide level in subgroup analysis within the obese group (body mass index ≥ 30.0 kg/m2).
SNPs at genome-wide level in subgroup analysis within the physically inactive group (<10 MET).
SNPs at genome-wide level in subgroup analysis within the low-fat diet group (<7.0% calories from SFA).