Table 5.

Genome-wide meta-analysis of overall test and/or interaction test with the stratified analysis for the association with hyperinsulinemia and multiple Cox regression for the genotypes of SNPs in MTRR and LOC729506 genes for predicting breast cancer risk, stratified by physical activity

Active group (MET ≥ 10)Inactive group (MET < 10)
Interaction test for PA(n = 4,658)(n = 6,451)
SNPaAllele (Ref/Alt)bPQORcPcQcHRd (95% CI)PORcPcQcHRd (95% CI)P
MTRR rs13182814CC + CT/TT2.18E−050.6440.950.3120.4560.93 (0.72–1.19)0.5591.279.90E−090.5471.25 (1.00–1.55)0.047
MTRR rs13163063AA + AC/CC2.93E−050.6370.950.3590.4490.93 (0.72–1.19)0.5561.278.83E−090.5551.25 (1.00–1.55)0.047
MTRR rs35009176GG + GA/AA2.85E−050.6500.950.3630.4520.93 (0.72–1.20)0.5641.277.82E−090.5621.25 (1.01–1.55)0.044
MTRR rs34411024AA + AG/GG2.44E−050.6370.950.3570.4390.93 (0.72–1.19)0.5621.276.14E−090.5531.25 (1.01–1.55)0.044
MTRR rs6555516TT + TA/AA2.92E−050.6340.950.4000.4550.92 (0.72–1.19)0.5411.274.99E−090.5551.25 (1.00–1.55)0.045
MTRR rs6555517AA + AG/GG2.74E−050.6500.950.3570.4520.93 (0.72–1.19)0.5611.277.82E−090.5621.25 (1.01–1.55)0.044
MTRR rs6555518TT + TC/CC2.77E−050.6380.950.3460.4840.93 (0.73–1.20)0.6011.278.26E−090.5271.24 (1.00–1.54)0.049
MTRR rs7447098AA + AG/GG2.77E−050.6380.950.3460.4840.93 (0.73–1.20)0.6011.278.26E−090.5271.24 (1.00–1.54)0.049
MTRR rs6555519AA + AT/TT4.02E−050.6760.950.3790.4750.93 (0.72–1.20)0.5851.271.23E−080.5461.25 (1.01–1.56)0.041
MTRR rs7447152AA + AG/GG3.05E−050.6020.950.3450.4580.93 (0.72–1.19)0.5521.279.55E−090.5281.25 (1.00–1.55)0.048
MTRR rs7444691GG + GT/TT3.05E−050.6020.950.3450.4580.93 (0.72–1.19)0.5521.279.55E−090.5281.25 (1.00–1.55)0.048
MTRR rs17131CC + CT/TT2.34E−050.6570.950.3430.4730.93 (0.72–1.19)0.5541.276.64E−090.5651.25 (1.01–1.55)0.045
MTRR rs13169903AA + AT/TT2.94E−050.6480.950.3440.4830.92 (0.72–1.19)0.5361.279.47E−090.5211.24 (1.00–1.54)0.049
MTRR rs1847915CC + CT/TT2.60E−050.6560.950.3640.4690.93 (0.72–1.20)0.5641.276.32E−090.5541.25 (1.01–1.55)0.043
MTRR rs6555520CC + CA/AA2.69E−050.6490.950.3640.4690.93 (0.72–1.20)0.5641.276.96E−090.5491.25 (1.01–1.55)0.043
MTRR rs6555521CC + CA/AA2.42E−050.6310.950.3230.4360.92 (0.72–1.19)0.5451.278.58E−090.5121.24 (1.00–1.54)0.049
LOC729506 rs2123640TT + TC/CC1.19E−050.6330.940.2850.3841.00 (0.78–1.29)0.9781.283.20E−090.5861.25 (1.00–1.55)0.047
LOC729506 rs7716902CC + CA/AA1.21E−050.6180.940.2890.3651.00 (0.78–1.29)0.9971.283.84E−090.5781.24 (1.00–1.55)0.049
LOC729506 rs13188458GG + GT/TT9.81E−060.6410.940.2810.3950.98 (0.76–1.27)0.9001.292.26E−090.4901.25 (1.01–1.56)0.043
LOC729506 rs13188952GG + GA/AA1.06E−050.6610.940.2860.4370.98 (0.76–1.26)0.8801.282.50E−090.4871.25 (1.01–1.56)0.043
LOC729506 rs10512942CC + CA/AA9.45E−060.6750.940.2810.4520.96 (0.74–1.24)0.7501.282.88E−090.4771.25 (1.00–1.56)0.045
LOC729506 rs34799743CC + CG/GG9.02E−060.6590.940.2570.4540.96 (0.74–1.24)0.7521.284.24E−090.4631.25 (1.01–1.56)0.044
LOC729506 rs13166872GG + GT/TT1.04E−050.6690.940.2820.4720.96 (0.74–1.24)0.7451.283.62E−090.4641.25 (1.00–1.56)0.045
LOC729506 rs17198862GG + GC/CC3.43E−050.6720.950.3240.4081.00 (0.78–1.29)0.9831.262.79E−080.5721.28 (1.03–1.59)0.028
  • NOTE: Only SNPs that are significantly genome-wide associated with hyperinsulinemia in overall/interaction (G*E or subgroup) analysis and breast cancer were included. Numbers in bold face are statistically significant.

  • Abbreviations: Alt, alternative allele; PA, physical activity; Ref, reference allele.

  • aAlthough SNPs were located between MTRR/LOC729506, the genes closest to the SNPs were selected.

  • bAll genetic models are recessive. Although additive models’ results are presented in genome-wide meta-analysis, the recessive model for each SNP had a similar effect size and P value.

  • cResults from genome-wide meta-analysis of interaction test for the association with HOMA-IR.

  • dHR adjusted by age, education, annual family income, family history of breast cancer, depressive symptom, smoking, dietary alcohol in g/day, % calories from SFAs/day, BMI, waist-to-hip ratio, hysterectomy ever, ages at menarche and menopause, oral contraceptive use, exogenous estrogen–only use, and exogenous estrogen plus progestin use.