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Table 3 Joint association of MTHFR C677T genotype and nutrient intakes on postmenopausal breast cancer risk, VITAL study *,†

From: MTHFR C677T and postmenopausal breast cancer risk by intakes of one-carbon metabolism nutrients: a nested case-control study

 

MTHFRC677T genotype

 

CC

CT

TT

  
 

Cases/controls

Multivariate OR (95% CI)

Cases/controls

Multivariate OR (95% CI)

Cases/controls

Multivariate OR (95% CI)

P for trend ‡

P for interaction §

Multivitamin use

        

   Some

92/218

1.00

108/213

1.20 (0.82-1.75)

29/51

1.46 (0.83-2.56)

0.24

 

   None

41/83

1.24 (0.75-2.03)

31/71

0.90 (0.52-1.59)

17/11

6.24 (2.37-16.4)

0.02

0.27

Folate

        

   Dietary folate (μg/day)

        

≥ 224 (median, high)

79/128

1.00

68/135

0.85 (0.55-1.30)

20/27

1.29 (0.66-2.52)

0.86

 

<224

43/139

0.41 (0.25-0.67)

55/126

0.60 (0.37-0.98)

26/27

1.31 (0.66-2.63)

<0.01

0.02

   Supplemental folate (μg/day) #

        

≥ 400

48/129

1.00

58/119

1.28 (0.80-2.06)

13/26

1.17 (0.54-2.54)

0.53

 

<400

85/172

1.34(0.87-2.07)

81/165

1.39 (0.89-2.15)

33/36

2.69 (1.48-4.88)

0.05

0.83

   Total folate (DFE/day)

        

≥ 850 (median, high)

54/132

1.00

65/127

1.26 (0.79-2.01)

13/29

1.03 (0.48-2.22)

0.74

 

<850

68/134

1.32 (0.83-2.09)

57/130

1.19 (0.74-1.91)

32/23

4.09 (2.08-8.04)

0.01

0.19

Methionine

        

   Dietary methionine (g/day)

        

≥ 1.38 (median, high)

60/133

1.00

56/135

0.91 (0.58-1.44)

19/23

1.89 (0.91-3.89)

0.29

 

<1.38

62/134

1.07 (0.65-1.77)

67/126

1.29 (0.78-2.13)

27/31

2.10 (1.07-4.14)

0.04

0.55

Vitamin B 2

        

   Dietary vitamin B2 (mg/day)

        

≥ 1.81 (median, high)

63/127

1.00

59/133

0.92 (0.58-1.44)

18/29

1.23 (0.62-2.45)

0.72

 

<1.81

59/140

0.85 (0.52-1.37)

64/128

1.03 (0.63-1.68)

28/25

2.53 (1.25-5.12)

<0.01

0.06

   Total vitamin B2 (mg/day)

        

≥ 2.70 (median, high)

59/125

1.00

60/139

0.94 (0.59-1.48)

16/26

1.27 (0.61-2.64)

0.96

 

<2.70

63/142

1.02(0.64-1.63)

63/122

1.23 (0.76-1.98)

39/28

2.73 (1.40-5.33)

0.02

0.10

Vitamin B 6

        

   Dietary vitamin B6 (mg/day)

        

≥ 1.61 (median, high)

59/129

1.00

54/132

0.93 (0.58-1.48)

16/31

1.20 (0.59-2.45)

0.97

 

<1.61

63/138

1.08 (0.66-1.77)

69/129

1.26 (0.77-2.07)

30/23

3.23 (1.58-6.61)

<0.01

0.07

   Supplemental vitamin B6 (mg/day) #

        

≥ 2.00

49/108

1.00

55/103

1.17 (0.72-1.90)

10/25

0.69 (0.30-1.60)

0.93

 

<2.00

84/192

0.87 (0.57-1.34)

83/177

0.97 (0.62-1.50)

36/35

2.31 (1.28-4.15)

<0.01

0.11

   Total vitamin B6 (mg/day)

        

≥ 3.32 (median, high)

57/132

1.00

62/130

1.11 (0.70-1.76)

12/32

0.72 (0.33-1.56)

0.83

 

<3.32

65/135

1.11 (0.70-1.75)

61/131

1.11 (0.70-1.76)

34/22

4.47 (2.28-8.75)

<0.01

0.01

Vitamin B 12

        

   Dietary vitamin B12 (μg/day)

        

≥ 5.30 (median, high)

52/131

1.00

57/133

1.13 (0.70-1.80)

19/26

2.01 (0.99-4.11)

0.15

 

<5.30

70/136

1.38 (0.85-2.22)

66/128

1.38 (0.85-2.26)

27/28

2.58 (1.31-5.08)

0.10

0.85

   Supplemental vitamin B12 (μg/day) #

        

≥ 6.00

56/120

1.00

69/109

1.30 (0.83-2.05)

14/25

1.06 (0.50-2.25)

0.44

 

<6.00

76/180

0.81 (0.53-1.24)

70/171

0.83 (0.54-1.29)

29/34

1.72 (0.94-3.15)

0.04

0.65

   Total vitamin B12 (μg/day)

        

≥ 11.4 (median, high)

60/130

1.00

69/131

1.17 (0.75-1.83)

17/33

1.15 (0.57-2.33)

0.48

 

<11.4

62/137

0.98 (0.62-1.53)

54/129

0.92 (0.58-1.47)

29/21

3.06 (1.55-6.04)

<0.01

0.17

Micronutrient score**

        

High (median)

57/129

1.00

62/134

1.09 (0.69-1.73)

13/27

1.05 (0.48-2.28)

0.96

 

Low

65/138

1.12 (0.70-1.80)

61/127

1.15 (0.71-1.87)

33/27

3.20 (1.66-6.19)

<0.01

0.10

Total alcohol (g/d)

        

<10.0 (low)

100/254

1.00

105/229

1.15 (0.81-1.65)

38/53

2.12 (1.26-3.56)

0.01

 

≥ 10.0

32/42

1.80 (1.02-3.15)

30/48

1.34 (0.76-2.38)

8/8

2.32 (0.79-6.85)

0.84

0.22

  1. * All analyses adjusted for the following:age (50-54 years, 55-59, 60-64, 65-69, 70-76), race (white, other), family history of breast cancer (no, 1 affected mother or sister, ≥ 2 affected mother or sister(s)), mammography within two years preceding baseline(no, yes), history of breast biopsy (no, yes), age at menarche (≤ 11 years,12,13, ≥ 14), age at first birth (nulliparous, ≤ 19 years, 20-24, 25-34, ≥ 35), age at menopause (≤ 44 years,45-49, ≥ 50), years of combined estrogen and progestin postmenopausal hormones (PMH, never or <1 years,1-4,5-9, ≥ 10), height (<62 in, 62-<65, 65-<68, ≥ 68), body mass index (BMI) (<25 kg/m2,25-<30, ≥ 30), total physical activity (none, 1-3 tertiles of MET-hours/week), total energy intake (kcal/day), and for non-alcohol exposures, past-year alcohol intake (<1.5 g/day, 1.5-4.9, 5.0-9.9, ≥ 10). Energy was added to the models for all dietary and total nutrient exposures.
  2. † Case/control numbers do not add up to total due to missing data on nutrient intakes
  3. ‡ P for trend testing trend for MTHFR genotypes by strata of nutrient/alcohol intakes and calculated by modelling the MTHFR genotypes (CC, CT, and TT) as one term, ordinally
  4. §P for interaction testing whether the association between MTHFR and breast cancer varies by nutrient/alcohol intake
  5. Median intakes, based on distribution of nutrient intake from controls
  6. # Intakes of all supplements over 10 years; cutpoints represent amount in a 10 year daily use of standard multivitamin or greater
  7. ** Micronutrient score computed by summing the z-scores of folate, methionine, and vitamins B2, B6, B12 and then, dividing this sum into high (upper median) and low (lower median) groups.