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Table 3.

Nrf2, NQO1, NOS3, and HO-1 genotype and breast cancer risk by use of multivitamins containing iron

Nonsupplement users
Supplement users,* total daily iron intake (10.5-98.2 mg)
AllTotal daily iron intake
4.8 to ≤9.6 mg
>9.6-22.5 mg
CaCoOR (95% CI)CaCoOR (95% CI)CaCoOR (95% CI)CaCoOR (95% CI)
Nrf2             
    CC 134 155 1 (referent) 74 77 1 (referent) 56 75 1 (referent) 95 95 1 (referent) 
    CT 100 90 1.31 (0.90-1.90) 54 51 1.18 (0.71-1.96) 46 38 1.66 (0.92-3.00) 75 62 1.28 (0.81-2.00) 
    TT 23 26 1.02 (0.55-1.90) 13 15 0.95 (0.41-2.19) 10 11 1.43 (0.54-3.78) 13 11 1.17 (0.48-2.83) 
   P trend = 0.43   P trend = 0.81   P trend = 0.15   P trend = 0.37 
NQO1             
    CC 171 167 1 (referent) 90 86 1 (referent) 77 77 1 (referent) 120 117 1 (referent) 
    CT 78 90 0.82 (0.56-1.19) 46 47 0.96 (0.57-1.61) 32 43 0.73 (0.41-1.32) 55 44 1.24 (0.77-2.01) 
    TT 11 0.57 (0.20-1.60) 0.52 (0.15-1.84) 0.93 (0.14-6.14) 0.97 (0.29-3.24) 
   P trend = 0.16   P trend = 0.46   P trend = 0.36   P trend = 0.52 
NOS3             
    GG 124 122 1 (referent) 69 61 1 (referent) 52 59 1 (referent) 88 84 1 (referent) 
    GT 105 118 0.91 (0.63-1.32) 52 63 0.75 (0.45-1.26) 52 53 1.19 (0.68-2.08) 67 67 0.99 (0.63-1.58) 
    TT 22 23 0.94 (0.49-1.79) 15 13 1.11 (0.48-2.56) 10 0.77 (0.26-2.32) 24 11 2.18 (0.99-4.81) 
   P trend = 0.67   P trend = 0.71   P trend = 0.94   P trend = 0.16 
HO-1             
    LS + MM + MS + SS 132 149 1 (referent) 76 78 1 (referent) 54 69 1 (referent) 80 94 1 (referent) 
    LL + LM 112 115 1.15 (0.80-1.65) 58 59 1.06 (0.64-1.74) 52 54 1.35 (0.77-2.35) 94 74 1.56 (1.01-2.41) 
High-risk alleles or genotypes§             
    0 26 31 1 (referent) 18 16 1 (referent) 14 1 (referent) 15 21 1 (referent) 
    1 63 71 1.03 (0.55-1.94) 31 34 0.90 (0.38-2.12) 29 35 1.86 (0.62-5.63) 50 54 1.37 (0.63-3.00) 
    2 97 89 1.28 (0.70-2.35) 50 50 0.95 (0.43-2.10) 47 39 3.06 (1.04-8.96) 53 53 1.55 (0.71-3.40) 
    3+ 72 81 1.08 (0.58-2.00) 43 43 1.08 (0.47-2.46) 29 37 1.90 (0.63-5.70) 65 42 2.39 (1.09-5.26) 
   P trend = 0.69   P trend = 0.73   P trend = 0.32   P trend = 0.02 
Nonsupplement users
Supplement users,* total daily iron intake (10.5-98.2 mg)
AllTotal daily iron intake
4.8 to ≤9.6 mg
>9.6-22.5 mg
CaCoOR (95% CI)CaCoOR (95% CI)CaCoOR (95% CI)CaCoOR (95% CI)
Nrf2             
    CC 134 155 1 (referent) 74 77 1 (referent) 56 75 1 (referent) 95 95 1 (referent) 
    CT 100 90 1.31 (0.90-1.90) 54 51 1.18 (0.71-1.96) 46 38 1.66 (0.92-3.00) 75 62 1.28 (0.81-2.00) 
    TT 23 26 1.02 (0.55-1.90) 13 15 0.95 (0.41-2.19) 10 11 1.43 (0.54-3.78) 13 11 1.17 (0.48-2.83) 
   P trend = 0.43   P trend = 0.81   P trend = 0.15   P trend = 0.37 
NQO1             
    CC 171 167 1 (referent) 90 86 1 (referent) 77 77 1 (referent) 120 117 1 (referent) 
    CT 78 90 0.82 (0.56-1.19) 46 47 0.96 (0.57-1.61) 32 43 0.73 (0.41-1.32) 55 44 1.24 (0.77-2.01) 
    TT 11 0.57 (0.20-1.60) 0.52 (0.15-1.84) 0.93 (0.14-6.14) 0.97 (0.29-3.24) 
   P trend = 0.16   P trend = 0.46   P trend = 0.36   P trend = 0.52 
NOS3             
    GG 124 122 1 (referent) 69 61 1 (referent) 52 59 1 (referent) 88 84 1 (referent) 
    GT 105 118 0.91 (0.63-1.32) 52 63 0.75 (0.45-1.26) 52 53 1.19 (0.68-2.08) 67 67 0.99 (0.63-1.58) 
    TT 22 23 0.94 (0.49-1.79) 15 13 1.11 (0.48-2.56) 10 0.77 (0.26-2.32) 24 11 2.18 (0.99-4.81) 
   P trend = 0.67   P trend = 0.71   P trend = 0.94   P trend = 0.16 
HO-1             
    LS + MM + MS + SS 132 149 1 (referent) 76 78 1 (referent) 54 69 1 (referent) 80 94 1 (referent) 
    LL + LM 112 115 1.15 (0.80-1.65) 58 59 1.06 (0.64-1.74) 52 54 1.35 (0.77-2.35) 94 74 1.56 (1.01-2.41) 
High-risk alleles or genotypes§             
    0 26 31 1 (referent) 18 16 1 (referent) 14 1 (referent) 15 21 1 (referent) 
    1 63 71 1.03 (0.55-1.94) 31 34 0.90 (0.38-2.12) 29 35 1.86 (0.62-5.63) 50 54 1.37 (0.63-3.00) 
    2 97 89 1.28 (0.70-2.35) 50 50 0.95 (0.43-2.10) 47 39 3.06 (1.04-8.96) 53 53 1.55 (0.71-3.40) 
    3+ 72 81 1.08 (0.58-2.00) 43 43 1.08 (0.47-2.46) 29 37 1.90 (0.63-5.70) 65 42 2.39 (1.09-5.26) 
   P trend = 0.69   P trend = 0.73   P trend = 0.32   P trend = 0.02 
*

Supplementary iron intake was based on iron intake from regular multivitamin use and divided into nonusers and users.

OR and 95% CI. All models were adjusted for age, family history of breast cancer (yes, no), hormone replacement therapy (yes, no), body mass index (continuous, log transformed), age at menarche, age at menopause, smoking status (ever/never), race (Caucasian, other), and parity (yes/no). Among controls, 63 were excluded from the analyses because of missing supplement information (n = 16) and missing covariate information (n = 47). An additional 8 participants (4 cases and 4 controls) were excluded from analyses assessing high and low iron intake among nonsupplement users because of missing dietary information. Among cases, 61 were excluded from the analysis because of missing supplement information (n = 17) and missing covariate information (n = 44).

P for multiplicative interaction comparing supplement users with all nonusers is P = 0.74 for Nrf2, P = 0.18 for NQO1, P = 0.19 for NOS3, P = 0.32 for HO-1 (LL + LM versus LS + MM + MS + SS), and P = 0.11 for total number of high-risk alleles or genotypes.

§

Sum total of high-risk alleles or genotypes, which were taken to be the Nrf2 T allele, the NQO1 T allele, the NOS3 T allele, and the HO-1 LL and LM genotypes.

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