Nrf2, NQO1, and HO-1 genotype and breast cancer risk by tertile of total (dietary and supplemental) iron intake
| . | Iron intake* . | . | . | . | . | . | . | . | . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | ≤9.6 mg/d . | . | . | >9.6-22.5 mg/d . | . | . | >22.5-98.2 mg/d . | . | . | |||||||||
| . | Ca . | Co . | OR (95% CI)† . | Ca . | Co . | OR (95% CI) . | Ca . | Co . | OR (95% CI) . | |||||||||
| Nrf2‡ | ||||||||||||||||||
| CC | 74 | 77 | 1 (referent) | 70 | 85 | 1 (referent) | 80 | 85 | 1 (referent) | |||||||||
| CT | 54 | 51 | 1.18 (0.71-1.96) | 57 | 47 | 1.47 (0.87-2.47) | 64 | 53 | 1.37 (0.84-2.22) | |||||||||
| TT | 13 | 15 | 0.95 (0.41-2.19) | 13 | 15 | 1.09 (0.47-2.52) | 10 | 7 | 1.69 (0.58-4.92) | |||||||||
| P trend = 0.81 | P trend = 0.37 | P trend = 0.15 | ||||||||||||||||
| NQO1 | ||||||||||||||||||
| CC | 90 | 86 | 1 (referent) | 96 | 94 | 1 (referent) | 101 | 100 | 1 (referent) | |||||||||
| CT | 46 | 47 | 0.96 (0.57-1.61) | 41 | 48 | 0.83 (0.49-1.40) | 45 | 39 | 1.16 (0.69-1.96) | |||||||||
| TT | 4 | 8 | 0.52 (0.15-1.84) | 2 | 5 | 0.46 (0.08-2.64) | 6 | 4 | 1.59 (0.41-6.13) | |||||||||
| P trend = 0.46 | P trend = 0.30 | P trend = 0.42 | ||||||||||||||||
| NOS3 | ||||||||||||||||||
| GG | 69 | 61 | 1 (referent) | 65 | 70 | 1 (referent) | 74 | 73 | 1 (referent) | |||||||||
| GT | 52 | 63 | 0.75 (0.45-1.26) | 65 | 63 | 1.11 (0.67-1.84) | 56 | 55 | 1.03 (0.62-1.71) | |||||||||
| TT | 15 | 13 | 1.11 (0.48-2.56) | 11 | 10 | 1.10 (0.42-2.88) | 20 | 11 | 1.92 (0.83-4.43) | |||||||||
| P trend = 0.71 | P trend = 0.70 | P trend = 0.23 | ||||||||||||||||
| HO-1 | ||||||||||||||||||
| LL | 45 | 45 | 1 (referent) | 50 | 47 | 1 (referent) | 50 | 48 | 1 (referent) | |||||||||
| LM | 13 | 14 | 0.79 (0.31-1.98) | 19 | 16 | 1.18 (0.53-2.65) | 20 | 17 | 1.00 (0.46-2.16) | |||||||||
| LS | 48 | 46 | 0.97 (0.53-1.78) | 36 | 60 | 0.53 (0.29-0.97) | 41 | 53 | 0.63 (0.35-1.11) | |||||||||
| MM | 2 | 5 | 0.33 (0.06-1.84) | 4 | 2 | 1.33 (0.21-8.38) | 3 | 3 | 0.78 (0.14-4.29) | |||||||||
| MS | 11 | 9 | 1.26 (0.47-3.42) | 11 | 7 | 1.34 (0.46-3.87) | 8 | 14 | 0.50 (0.19-1.33) | |||||||||
| SS | 15 | 18 | 0.69 (0.30-1.60) | 12 | 15 | 0.77 (0.31-1.86) | 19 | 9 | 1.69 (0.69-4.16) | |||||||||
| LS + MM + MS + SS | 76 | 78 | 1 (referent) | 63 | 84 | 1 (referent) | 71 | 79 | 1 (referent) | |||||||||
| LL + LM | 58 | 59 | 1.06 (0.64-1.74) | 69 | 63 | 1.59 (0.96-2.63) | 76 | 65 | 1.36 (0.85-2.18) | |||||||||
| High-risk alleles or genotypes§ | ||||||||||||||||||
| 0 | 18 | 16 | 1 (referent) | 8 | 17 | 1 (referent) | 14 | 18 | 1 (referent) | |||||||||
| 1 | 31 | 34 | 0.90 (0.38-2.12) | 37 | 39 | 2.26 (0.83-6.17) | 42 | 50 | 1.13 (0.49-2.58) | |||||||||
| 2 | 50 | 50 | 0.95 (0.43-2.10) | 55 | 49 | 2.83 (1.06-7.53) | 44 | 43 | 1.51 (0.65-3.47) | |||||||||
| 3+ | 43 | 43 | 1.08 (0.47-2.46) | 40 | 44 | 2.24 (0.83-6.04) | 54 | 35 | 2.27 (0.97-5.29) | |||||||||
| P trend = 0.73 | P trend = 0.26 | P trend = 0.02 | ||||||||||||||||
| . | Iron intake* . | . | . | . | . | . | . | . | . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | ≤9.6 mg/d . | . | . | >9.6-22.5 mg/d . | . | . | >22.5-98.2 mg/d . | . | . | |||||||||
| . | Ca . | Co . | OR (95% CI)† . | Ca . | Co . | OR (95% CI) . | Ca . | Co . | OR (95% CI) . | |||||||||
| Nrf2‡ | ||||||||||||||||||
| CC | 74 | 77 | 1 (referent) | 70 | 85 | 1 (referent) | 80 | 85 | 1 (referent) | |||||||||
| CT | 54 | 51 | 1.18 (0.71-1.96) | 57 | 47 | 1.47 (0.87-2.47) | 64 | 53 | 1.37 (0.84-2.22) | |||||||||
| TT | 13 | 15 | 0.95 (0.41-2.19) | 13 | 15 | 1.09 (0.47-2.52) | 10 | 7 | 1.69 (0.58-4.92) | |||||||||
| P trend = 0.81 | P trend = 0.37 | P trend = 0.15 | ||||||||||||||||
| NQO1 | ||||||||||||||||||
| CC | 90 | 86 | 1 (referent) | 96 | 94 | 1 (referent) | 101 | 100 | 1 (referent) | |||||||||
| CT | 46 | 47 | 0.96 (0.57-1.61) | 41 | 48 | 0.83 (0.49-1.40) | 45 | 39 | 1.16 (0.69-1.96) | |||||||||
| TT | 4 | 8 | 0.52 (0.15-1.84) | 2 | 5 | 0.46 (0.08-2.64) | 6 | 4 | 1.59 (0.41-6.13) | |||||||||
| P trend = 0.46 | P trend = 0.30 | P trend = 0.42 | ||||||||||||||||
| NOS3 | ||||||||||||||||||
| GG | 69 | 61 | 1 (referent) | 65 | 70 | 1 (referent) | 74 | 73 | 1 (referent) | |||||||||
| GT | 52 | 63 | 0.75 (0.45-1.26) | 65 | 63 | 1.11 (0.67-1.84) | 56 | 55 | 1.03 (0.62-1.71) | |||||||||
| TT | 15 | 13 | 1.11 (0.48-2.56) | 11 | 10 | 1.10 (0.42-2.88) | 20 | 11 | 1.92 (0.83-4.43) | |||||||||
| P trend = 0.71 | P trend = 0.70 | P trend = 0.23 | ||||||||||||||||
| HO-1 | ||||||||||||||||||
| LL | 45 | 45 | 1 (referent) | 50 | 47 | 1 (referent) | 50 | 48 | 1 (referent) | |||||||||
| LM | 13 | 14 | 0.79 (0.31-1.98) | 19 | 16 | 1.18 (0.53-2.65) | 20 | 17 | 1.00 (0.46-2.16) | |||||||||
| LS | 48 | 46 | 0.97 (0.53-1.78) | 36 | 60 | 0.53 (0.29-0.97) | 41 | 53 | 0.63 (0.35-1.11) | |||||||||
| MM | 2 | 5 | 0.33 (0.06-1.84) | 4 | 2 | 1.33 (0.21-8.38) | 3 | 3 | 0.78 (0.14-4.29) | |||||||||
| MS | 11 | 9 | 1.26 (0.47-3.42) | 11 | 7 | 1.34 (0.46-3.87) | 8 | 14 | 0.50 (0.19-1.33) | |||||||||
| SS | 15 | 18 | 0.69 (0.30-1.60) | 12 | 15 | 0.77 (0.31-1.86) | 19 | 9 | 1.69 (0.69-4.16) | |||||||||
| LS + MM + MS + SS | 76 | 78 | 1 (referent) | 63 | 84 | 1 (referent) | 71 | 79 | 1 (referent) | |||||||||
| LL + LM | 58 | 59 | 1.06 (0.64-1.74) | 69 | 63 | 1.59 (0.96-2.63) | 76 | 65 | 1.36 (0.85-2.18) | |||||||||
| High-risk alleles or genotypes§ | ||||||||||||||||||
| 0 | 18 | 16 | 1 (referent) | 8 | 17 | 1 (referent) | 14 | 18 | 1 (referent) | |||||||||
| 1 | 31 | 34 | 0.90 (0.38-2.12) | 37 | 39 | 2.26 (0.83-6.17) | 42 | 50 | 1.13 (0.49-2.58) | |||||||||
| 2 | 50 | 50 | 0.95 (0.43-2.10) | 55 | 49 | 2.83 (1.06-7.53) | 44 | 43 | 1.51 (0.65-3.47) | |||||||||
| 3+ | 43 | 43 | 1.08 (0.47-2.46) | 40 | 44 | 2.24 (0.83-6.04) | 54 | 35 | 2.27 (0.97-5.29) | |||||||||
| P trend = 0.73 | P trend = 0.26 | P trend = 0.02 | ||||||||||||||||
Energy-adjusted daily total iron intake (diet and supplement) was calculated as energy-adjusted dietary intake plus iron intake from multivitamin supplement use. Intake categories represent tertile of intake in the control group.
OR and 95% CI calculated by unconditional logistic regression 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), parity (yes/no). Among controls, 67 were excluded from the analyses because of missing diet information (n = 21) and missing covariate information (n = 46). Among cases, 66 were excluded from the analysis because of missing diet information (n = 22) and missing covariate information (n = 44).
To test multiplicative interactions, a cross-product term for genotype (as a continuous variable indicating number of variant alleles) and iron intake (tertile group) was included in multivariate models. P for multiplicative interaction is P = 0.57 for Nrf2, P = 0.36 for NQO1, P = 0.55 for NOS3, P = 0.52 for HO-1 (LL + LM versus LS + MM + MS + SS), and P = 0.30 for total number of at-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 NOS T allele, and the HO-1 LL and LM genotypes.