Title: Retinol, Vitamins A, C and E and Breast Cancer Risk: a Meta-Analysis and Meta-Regression

Title: Retinol, vitamins A, C and E and breast cancer risk: a meta-analysis and meta-regression

Journal: Cancer cause and control

Authors:Hu Fulan, Jiang Changxing, WangYi Baina, Zhang Wencui, Lin Chunqing, Wang Fan, Li Dandan,Sun Dianjun, Wang Tong, Pang Da, Zhao Yashuang

Corresponding author: Zhao Yashuang PhD

Department of Epidemiology, PublicHealthCollege, HarbinMedicalUniversity.

Address: 157, Baojian Street, Nangang District, Harbin, Department of Epidemiology, PublicHealthCollege, Harbin Medical University, Heilongjiang Province, P. R. China.

Tel： 0086-(0)451-87502823

Fax: 0086-(0)451-87502885

E-mail：

Corresponding author: Pang Da PhD

Department of Breast Surgery, Third Affiliated Clinical Hospital of HarbinMedical University,HeilongjiangProvince, P. R. China.

Address: 150, Haping Street, Nangang District, Harbin, Department of Breast Surgery, Third Affiliated Clinical Hospital of Harbin Medical University,Harbin, Heilongjiang Province, P. R. China.

Tel： 0086-(0) 451－86298613

Fax： 0086-(0) 451－6663760

E-mail：

Zhao Yashuang and Pang Da et al

SupplementalTable 1. Characteristics of included articles about the associations between retinol, vitamins A, C and E and the risk of breast cancer arranged by Study Design

Reference / Country ( continent) / Cases/controls or cohort size / Baseline information / Vitamins / Intake level / OR (95%CI) or
RR (95%CI) / Adjustment variables
Case Control Studies-Hospital Based (23)
Adzersen KH (2003)[12] / Germany (Europe) / 310/353 / Recruitment: 1998-1999;
Age: 25-75 y;
FFQ (121 items);
Time frame*: in general
Menopause status: All / Vitamin C
(mg/day) / 58.5-93.0 v.s. <58.5 / 1.42 (0.88, 2.28) / Age; BMI; total energy;
age at menarche- first birth and menopause; family history of breast cancer; history of benign breast disease and/or operation; alcohol consumption; HRT.
93.0-134.4 v.s. <58.5 / 1.08 (0.66, 1.77)
>134.4 v.s. <58.5 / 0.49 (0.28, 0.88)
Vitamin E
(mg/day) / 7.1-9.5 v.s. <7.1 / 1.08 (0.64, 1.82)
9.5-12.7 v.s. <7.1 / 1.09 (0.62, 1.93)
>12.7 v.s. <7.1 / 1.08 (0.58, 2.03)
Bohlke K (1999) [10] / Greece (Europe) / 820/1548 / Recruitment: 1989-1991;
Age: all women;
FFQ (115 items);
Time frame*: 1 year prior
Menopause status:
All (pre-and post-) / Retinol
(µg/day) / 659.2-1306.3 v.s. <=659.1 / All: 0.99 (0.73, 1.33)
Pre: 1.26 (0.71, 2.26)
Post: 0.89 (0.63, 1.27) / Age; BMI; total nergy;
age at menarche;
age at first birth;
birth place;
menopause status;
parity.
1306.4-1575.2 v.s. <=659.1 / All: 1.03 (0.76, 1.39)
Pre: 1.28 (0.73, 2.24)
Post: 0.91 (0.64, 1.31)
1575.3-2120.7 v.s. <=659.1 / All: 0.84 (0.61, 1.15)
Pre: 1.18 (0.67, 2.05)
Post: 0.68 (0.46, 1.01)
>2120.7 v.s. <=659.1 / All: 0.89 (0.65, 1.23)
Pre: 1.16 (0.67, 2.01)
Post: 0.80 (0.53, 1.21)
Vitamin C
(mg/day) / 143.0-212.0
v.s. <=142.9 / All: 1.25 (0.92, 1.69)
Pre: 0.95 (0.54, 1.67)
Post: 1.38 (0.96, 1.98)
212.1-274.0 v.s. <=142.9 / All: 0.96 (0.69, 1.33)
Pre: 0.96 (0.53, 1.72)
Post: 0.91 (0.61, 1.36)
274.1-343.1 v.s. <=142.9 / All: 0.83 (0.60, 1.17)
Pre: 0.61 (0.33, 1.11)
Post: 0.93 (0.61, 1.41)
>343.1 v.s. <=142.9 / All: 0.68 (0.47, 0.97)
Pre: 0.45 (0.24, 0.85)
Post: 0.80 (0.51, 1.26)
Vitamin E
(IU/day) / 5.3-6.2 v.s. <=5.2 / All: 0.90 (0.65, 1.24)
Pre: 0.86 (0.47, 1.59)
Post: 0.88 (0.59, 1.30)
6.3-7.2 v.s. <=5.2 / All: 0.89 (0.64, 1.26)
Pre: 1.00 (0.53, 1.90)
Post: 0.80 (0.53, 1.21)
7.3-8.6 v.s. <=5.2 / All: 0.65 (0.45, 0.95)
Pre: 0.68 (0.35, 1.33)
Post: 0.61 (0.38, 0.96)
>8.6 v.s. <=5.2 / All: 0.71 (0.48, 1.05)
Pre: 0.50 (0.25, 1.02)
Post: 0.85 (0.53, 1.36)
Bonilla-Femandez P (2003)[29] / USA (America) / 141/141 / Recruitment: 1994-1996;
Age: 21-79y;
FFQ（95 items);
Time frame*: 1 year prior;
Menopause status: All (pre-and post-) / Vitamin A
(IU/day) / 7782.9-13370 v.s. <=7731.8 / All:0.91 (0.45, 1.87)
Pre: 1.00 (0.39, 2.55)
Post:0.94 (0.36, 2.44) / Energy; quetelet index; age of menarche; age at interview; totalbreastfeeding;family history of breast cancer;
age at first birth and parity; and nulliparous
13407-41447 v.s. <=7731.8 / All :0.53 (0.21, 1.33)
Pre: 0.51 (0.17, 1.54)
Post: 1.09(0.34, 3.50)
Vitamin E
(α-Tocopherol equivalent) / 17.59-23.28 v.s.
<=17.58 / All:0.80 (0.41, 1.57)
Pre: 1.00 (0.36, 2.77)
Post:0.57(0.20, 1.56)
23.32-40.51 v.s. <=17.58 / All:0.68 (0.30, 1.53)
Pre:1.86 (0.59, 5.83)
Post:0.10(0.02, 0.44)
Do MH (2003)[16] / Korea (Asia) / 224/250 / Recruitment: 1999-2000;
Age:20-69 y;
FFQ(84 items);
Time frame: 12 months period of 3 yr prior;
Menopause status: All; / Vitamin A
(retinol equivalent) / 1553.24-2702.39 v.s. <1553.24 / 0.71 (0.26, 1.91) / age at menarche; total menstrual periods;
pregnancy; total number of full term delivery; total periods of breast
feeding; family history of breast cancer and current BMI
≥2702.40 v.s. <1553.24 / 0.89 (0.09, 1.69)
Retinol (µg/day) / 40.91-105.77<40.91 / 0.78 (0.31, 1.17)
≥105.78<40.91 / 0.88 (0.26, 1.09)
Vitamin C (mg/day) / 100.2-210.72 v.s. <100.20 / 0.54 (0.39, 1.01)
≥210.73 v.s. <100.20 / 0.37(0.19, 0.84)
Vitamin E (mg/day) / 6.26-12.71 v.s. <6.26 / 0.71 (0.39, 1.27)
≥12.71 v.s. <6.26 / 0.81 (0.44, 1.88)
Graham S (1982)[47] / USA (America) / 2024/1463 / Recruitment: 1958-1965;
Age: unspecified;
Self-administered questionnaire;
Time frame:prior to diagnosis;
Menopause status: All; / Vitamin C
(mg/ month) / 1401-1800 v.s. >1800 / 1.12 / No adjustment factors
1001-1400 v.s. >1800 / 1.09
1000 v.s. >1800 / 0.92
Vitamin A
(IU/month) / 100,501-150,500 v.s. >150,500 / All:1.11
<55: 0.84
≥55: 1.43
50,501-100,500 v.s.
>150,500 / All: 1.18
<55: 0.98
≥55: 1.38
550,500 v.s. >150,500 / All: 1.33
<55: 1.1
≥55: 1.53
Katsouyanni K(1988)[48] / Greece (Europe) / 120/120 / Recruitment: 1983-1984;
Age: unspecified;
FFQ (120items);
Time frame:period preceding the onset of disease;
Menopause status: All; / Vitamin A
(IU/day) / 6269-8111 v.s. <=6268 / 0.80 (0.35, 0.85) / Panty; age at first birth; menopausal status; age at
Menarche; age at menopause; place of residence; marital status; and
other significant nutrients
8112-9762 v.s. <=6268 / 0.59 (0.26, 1.33)
9763-12481 v.s. <=6268 / 0.56 (0.24, 1.28)
>12483 v.s. <=6268 / 0.40 (0.17, 0.93)
Landa MC (1994)[38] / Spain (Europe) / 100/100 / Recruitment: 1987-1988;
Age: unspecified;
FFQ (99 items);
Time frame: average;
Menopause status: All; / Vitamin A
(µg/day) / Q2 v.s. Q1 / 0.17 (0.1, 0.3) / energy
Q3 v.s. Q1 / 0.40 (0.2, 0.9)
Vitamin C
(µg/day) / Q2 v.s. Q1 / 1.2 (2.5, 0.6)
Q3 v.s. Q1 / 0.94 (0.38, 3.2)
Lee MM (2005)[31] / China (Asia) / 250/219 / Recruitment: 1996-1999;
Age: 25-79 y;
Time frame:1 year prior for cases, last year prior
interviews for controls;
FFQ(100 items);
Menopause status: All; / Vitamin A
(RE/d/kcal) / 1.1-1.6 v.s. <1.1 / All: 0.8 (0.5, 1.3)
≤40: 0.6 (0.3, 1.4)
>40: 0.9 (0.5, 1.8) / Age;education.
1.7-2.6 v.s. <1.1 / All: 0.6 (0.3, 0.9)
≤40: 0.6 (0.2, 1.3)
>40: 0.5 (0.3, 1.1)
>2.6 v.s. <1.1 / All: 0.7 (0.4, 1.1)
≤40: 0.6 (0.3, 1.4)
>40: 0.7 (0.3, 1.3)
Vitamin E
(a-TE/d/kcal) / 2.4-3.1 v.s. <2.4 / All: 0.8 (0.5, 1.3)
≤40: 1.2 (0.5, 2.5)
>40: 0.6 (0.3, 1.1)
3.2-3.9 v.s. <2.4 / All: 0.9 (0.5, 1.5)
≤40: 1.0 (0.4, 2.4)
>40: 0.8 (0.4, 1.7)
>3.9 v.s. <2.4 / All: 0.8 (0.4, 1.3)
≤40: 1.1 (0.5, 2.8)
>40: 0.6 (0.3, 1.2)
Vitamin C
(mg/d/kcal) / 88-121 v.s. <88 / All: 0.7 (0.4, 1.2)
≤40: 0.9 (0.4, 1.9)
>40: 0.7 (0.4, 1.3)
122-168 v.s. <88 / All: 0.5 (0.3, 0.9)
≤40: 0.6 (0.2, 1.3)
>40: 0.5 (0.3, 1.0)
>168 v.s. <88 / All: 0.5 (0.3, 0.9)
≤40: 0.3 (0.1, 0.7)
>40: 0.7 (0.3, 1.3)
Lee HP (1991)[49] / Singapore (Asia) / 200/420 / Recruitment: 1986-1988;
Age: 24-88y;
FFQ (90 items);
Time frame: 1 year prior;
Menopause status: All; / Vitamin E
(mg/day) / 3.2-3.9 v.s.<3.1 / 0.83 (0.45, 1.56) / Age; age at first birth; including nulliparous as a category
4.0-4.8 v.s. <3.1 / 0.58 (0.31, 1.08)
Levi F (1993)[52] / Switzerland (Europe) / 107/318 / Recruitment: 1990-1992;
Age: 32-75 y;
structured questionnaire(50 items);
Time frame: unspecified;
Menopause status: All / Retinol
(IU/day) / 46.2-143.4 v.s. <46.2 / 0.9 (-) / Age; education; total energy intake.
>143.4 v.s. <46.2 / 1.00 (-)
Ascorbic acid
(g/month) / 2.63-3.56 v.s. <2.63 / 0.9 (-)
>3.56 v.s. <2.63 / 0.7 (-)
Levi F (2001) [14] / Switzerland (Europe) / 289/442 / Recruitment: 1993-1999;
Age: 23–74 y;
FFQ (79 items);
Time frame: 2 years prior;
Menopause status: All (pre-and post-). / Retinol (mg/day) / 307.5 v.s. 147.4 / All: 1.46 (0.94, 2.27) / Age; education; parity; menopausal status; body mass index; totalenergy intake; and alcohol drinking.
2098.8 v.s. 147.4 / All: 1.12 (0.72, 1.76)
Vitamin C
(mg/day) / 137.8 v.s. 84.3 / All: 0.36 (0.24, 0.54)
208.6 v.s. 84.3 / All: 0.19 (0.12, 0.30)
Vitamin E
(mg/day) / 13.8 v.s. 9.4 / All: 0.62 (0.41, 0.92)
18.1 v.s. 9.4 / All: 0.37 (0.23, 0.59)
London SJ (1992)[50] / USA (America) / 377/403 / Recruitment: 1986-1988;
Age：64y (median);
FFQ (116 items);
Time frame: past year;
Menopause status: post / Retinol
IU/day
Total / 1205 v.s. 639 / 1.0 (0.6, 1.7) / Caloric intake; age; alcohol intake; age at first birth; parity; family history of breastcancer; age at menopause; age at menarche; prior history of benign breast disease;
body weight.
2373 v.s. 639 / 1.2 (0.7, 2.0)
4861 v.s. 639 / 1.1 (0.7, 1.9)
10916 v.s. 639 / 0.6 (0.3, 1.1)
Retinol
IU/day
Food only / 911 v.s. 555 / 1.0 (0.6, 1.7)
1462 v.s. 555 / 1.4 (0.8, 2.4)
2352 v.s. 555 / 0.9 (0.5, 1.6)
4358 v.s. 555 / 0.9 (0.5, 1.6)
Vitamin E
mg/day
Total / 7.4 v.s. 5.8 / 1.0 (0.6, 1.7)
9.2 v.s. 5.8 / 0.7 (0.4, 1.3)
20.5 v.s. 5.8 / 0.5 (0.3, 1.0)
368.1 v.s. 5.8 / 0.7 (0.4, 1.3)
Vitamin E
mg/day
Food only / 6.7 v.s. 5.4 / 0.8 (0.5, 1.4)
7.6 v.s. 5.4 / 0.9 (0.5, 1.5)
8.6 v.s. 5.4 / 0.7 (0.4, 1.2)
11 v.s. 5.4 / 0.4 (0.2, 0.9)
Mannisto S (1999) [24] / Finland (Europe) / 310/454 / Recruitment: 1990-1995;
Age: 25–75y;
FFQ (110 items);
Time frame: the preceding 12 months;
menopausal status: pre. / Dietary Retinol (µg/day) / 2737 v.s. 363 / 0.6 (0.3, 1.4) / Age; area; age at menarche, and first full-term pregnancy; use of oral contraceptives; estrogen replacement therapy; first degree history of breast cancer; history of benign breast disease; level of education; current alcohol intake; smoking habits; leisure activity and waist to hip ratio.
Total Retinol (µg/day) / 2750 v.s. 381 / 0.7 (0.3, 1.5)
Dietary vitamin C (mg/day) / 194 v.s. 86 / 1.3 (0.6, 2.9)
Total vitamin C (mg/day) / 209 v.s. 89 / 1.1 (0.5, 2.4)
Dietary vitamin E (mg/day) / 13 v.s. 7 / 1.1 (0.53, 2.6)
Total vitamin E (mg/day) / 13 v.s. 7 / 1.1 (0.5, 2.6)
Marubini E (1988) [40] / Italy (Europe) / 214/215 / Recruitment: 1982-1985;
Age: 30–65y;
FFQ (69 items);
Time frame: usual;
menopausal status: all; / Dietary Retionl (IU/day) / Q2 v.s. Q1 / 1.1 (0.5, 2.2) / Age; education; age at menarche, first birth, and menopause; parity; Quetelet index; family history of breast cancer; cholesterol; triglyceride blood level.
Q3 v.s. Q1 / 1.5 (0.8, 2.8)
Q4 v.s. Q1 / 0.9 (0.4, 1.7)
Q5 v.s. Q1 / 0.7 (0.4, 1.5)
Negri E (1996)[46] / Italy (Europe) / 2569/2588 / Recruitment: 1991-1994;
Age:23–74 y;
FFQ(78 items);
Time frame: 2 yearsbefore diagnosis;
menopausal status: all; / Vitamin A
(µg/day) / 707-949 v.s. <706 / 1.0 (0.8, 1.2) / Age; center; education; parity; energy and alcohol intake.
950-1303 v.s. <706 / 0.86 (0.7, 1.0)
1304-2361 v.s. <706 / 0.83 (0.7, 1.0)
>2361 v.s. <706 / 0.73 (0.6, 0.9)
Retinol
(µg/day) / 136-199 v.s. <135 / 1.0 (0.8, 1.2)
200-298 v.s. <135 / 1.08 (0.9, 1.3)
299-1598 v.s. <135 / 1.08 (0.9, 1.3)
>1598 v.s. <135 / 0.86 (0.7, 1.0)
Vitamin E
(mg/day) / 7.22-9.12 v.s. <7.22 / 1.0 (0.8, 1.2)
9.13-10.82 v.s. <7.22 / 0.89 (0.7, 1.1)
10.83-13.43 v.s. <7.22 / 0.93 (0.8, 1.1)
>13.43 v.s. <7.22 / 0.69 (0.6, 0.8)
Vitamin C
(mg/day) / 82-109 v.s.81 / 0.93 (0.8, 1.1)
110-138 v.s.81 / 0.96 (0.8, 1.2)
139-182 v.s.81 / 0.99 (0.8, 1.2)
>182 v.s.81 / 0.81 (0.7, 1.0)
Potischman N (1990) [39] / USA (America) / 83/113 / Recruitment: 1985-1986;
Age: 30–80 y;
self-administered questionnaire (30 items);
Time frame: dietary practices;
menopausal status: all; / Total Vitamin A
(IU/day) / low v.s. high / 1.35 (0.50, 3.60) / Age; age at first birth; family history; age at menarche;quetelet index; parity; age at menopause; income; maritalstatus.
Vegetable Vitamin A (IU/day) / low v.s. high / 1.27 (0.44, 3.67)
Qi XY (1994)[51] / China (Asia) / 244/244 / Recruitment: 1986-1987;
Age: unspecified;
FFQ (40 items);
Time frame: 1 yearsbefore the first diagnosis;
Menopause: all. / Vitamin C
(mg/day) / 100-140 v.s. <100 / 0.99 (0.55, 1.77) / total calories; fat
>140 v.s.<100 / 0.31 (0.17, 0.55)
Richardson S(1991)[53] / France (Europe) / 409/525 / Recruitment: 1983-1987;
Age: 30–80 y;
Dietaryquestionnaire (55 items);
Time frame: usual;
Menopause status: All (pre-and post-). / Retinol
(g/week) / 3.11-11.37 v.s. <=3.11 / All:1.5(1.1-2.1)
Pre:1.8(1.0-3.3)
Post:1.4 (0.9-2.2) / Age; family history; age at menopause; age at menarche; age at first full-term pregnancy; education.
> 11.37 v.s. <=3.11 / All:1.5(1.0-2.1)
Pre:1.3(0.7-2.4)
Post:2.8 (1.2-2.8
Vitamin E
(g/week) / 98-170 v.s. <=98 / All:1.2 (0.8-1.7)
Pre:1.2 (0.6-2.1)
Post:1.2 (0.7-1.8)
>170 v.s. <=98 / All:1.3 (0.9-1.8)
Pre:1.2 (0.7-2.2)
Post:1.3 (0.8-2.0
Ronco A (1999)[11] / Uruguay (America) / 400/405 / Recruitment: 1994-1997;
Age: all women;
FFQ (64 items);
Time frame: unspecified;
Menopause status: All / Vitamin C
(mg/day) / 71.3-92 v.s. <71.3 / 0.78 ( 0.50, 1.23) / Age; residence; urban/rural status; family history of breast cancer in a 1st-degree relative; body mass index; age at menarche; parity; menopausal status; total energy; and total vegetable intakes plus each nutrient.
92-124.9 v.s. <71.3 / 0.82 (0.50, 1.33)
>124.9 v.s. <71.3 / 0.62 (0.36, 1.05)
Vitamin E
mg/day / 4.7-6.4 v.s. <4.7 / 0.58 (0.38, 0.91)
6.4-9.1 v.s. <4.7 / 0.58 (0.37, 0.92)
>9.1 v.s. <4.7 / 0.5 (0.30, 0.82)
Suzana S (2008)[26] / Malaysia (Asia) / 57/139 / Recruitment: unspecified;
Age: 30 to 66y;
FFQ( 14 items);
Time frame: prior diagnosis;
Menopause status: all / Vitamin A
(µg/day) / 510.7-829.2 v.s.<510.7 / 2.81 (1.44-5.47) / No adjustment factor
829.2-1202 v.s. <510.7 / 1.51 (0.78-2.94)
>1202 v.s. 510.7 / 1.34 (0.66-2.75)
Vitamin E
(mg/day) / 5.8-8.6 v.s. <5.8 / 2.32 (1.20-4.48)
8.6-10.3 v.s. <5.8 / 2.18 (1.07-4.44)
>10.3 v.s. <5.8 / 2.14 (0.95-4.83)
Vecchia CL (1987) [54] / Italy (Europe) / 1108/1281 / Recruitment: 1983-1985;
Age: 26-74y;
Standard questionnaire;
Time frame: unspecified;
Menopause status: all. / Retinol (1000IU/ month) / 100-150 v.s. <100 / 0.91 (0.87, 1.39) / Age; hormonal and gynecological features; age at menarche, menopause and menstrual pattern; number of births; miscarriages; age at first pregnancy and at first and last birth; oral contraceptives and femal hormones.
>150 v.s. <100 / 0.89 (0.73, 1.08)
Zaridze D (1991)[37] / Russia (Europe) / 139/139 / Recruitment: 1987-1989;
Age: all women;
FFQ( 145 items);
Time frame: the year prior diagnosis;
Menopause status: post. / Retinol / Q2 v.s. Q1 / 1.24 (0.40, 3.80) / Energy intake; age at menarche and education.
Q3 v.s. Q1 / 0.93 (0.28, 3.05)
Q4 v.s. Q1 / 0.5 (0.11, 1.73）
Vitamin C / Q2 v.s. Q1 / 0.33 (0.09, 1.21)
Q3 v.s. Q1 / 0.12 (0.03, 0.49)
Q4 v.s. Q1 / 0.2 (0.06, 0.70)
Zhang CX (2009)[28] / China (Asia) / 438/438 / Recruitment: 2007-2008;
Age: 25-70 y;
FFQ ( 81 items):
Time frame:1 year prior;
Menopause status: all. / Vitamin A / Q2 v.s. Q1 / 0.64 (0.44, 0.93) / age at menarche; BMI; history of benign breast disease; mother/ sister/ daughter with breast cancer; physical activity; passive smoking and total energy intake.
Q3 v.s. Q1 / 0.42 (0.28, 0.63)
Q4 v.s. Q1 / 0.31 (0.20, 0.48)
Retinol / Q2 v.s. Q1 / 0.76 (0.51, 1.14)
Q3 v.s. Q1 / 0.85 (0.57, 1.27)
Q4 v.s. Q1 / 0.76 (0.50, 1.15)
Vitamin C / Q2 v.s. Q1 / 0.56 (0.38, 0.82)
Q3 v.s. Q1 / 0.43 (0.29, 0.64)
Q4 v.s. Q1 / 0.30 (0.19, 0.46)
Vitamin E / Q2 v.s. Q1 / 0.62 (0.42, 0.92)
Q3 v.s. Q1 / 0.50 (0.33, 0.76)
Q4 v.s. Q1 / 0.31 (0.19, 0.50)
Case Control Studies-Population Based (13)
Challier B (1998)[20] / French (Europe) / 345/345 / Recruitment: 1986-1989;
Age: 30 to 78 y;
self-administered FFQ (38 itmes);
Time frame: most stable period;
Menopause status: all. / Vitamin E
(mg/day) / 6.3-8.0 v.s. <=6.2 / 1.15 (0.68, 1.92) / total calory intake; parity; weight and corporeal surface.
8.1-9.7 v.s. <=6.2 / 1.17 (0.69, 1.98)
9.8-11.7 v.s. <=6.2 / 0.96 (0.56, 1.66)
>11.8 v.s. <=6.2 / 1.54（0.87, 2.71）
Vitamin C
(mg/day) / 78.5-102.8 v.s. <=78.4 / 1.54 (0.91, 2.61)
102.9-128.3 v.s. <=78.4 / 1.50 (0.89, 2.54)
128.4-154.2 v.s. <=78.4 / 1.37 (0.81, 2.32)
154.2 v.s. <=78.4 / 1.48 (0.86, 2.55)
Retinol
(mg/day) / 0.30-0.35 v.s. <=0.29 / 0.76(0.43-1.31)
0.36-0.43 v.s. <=0.29 / 1.28(0.76, 2.16)
0.44-0.57 v.s. <=0.29 / 1.5(0.89, 2.53)
>0.57 v.s. <=0.29 / 1.4 (0.80, 2.47)
DorjgochooT (2008)[18] / China (Asia) / 3454/3474 / Recruitment: 1996-1998 and 2002-2004;
Age: 20-70y;
FFQ (>85% Chinese food);
Time frame: 5 year prior diagnosis;
Menopause status: all / vitamin A supplement / ever v.s. never / 1.0 (0.8, 1.2) / Age; education; age at menarche; live birth; BMI; menopausal status;
exercise participation in last 10 years; history of fibroadenoma; breast cancer risk in first-degree relatives
and study phase.
vitamin E supplement / ever v.s. never / 0.9 (0.8, 1.0)
vitamin C supplement / ever v.s. never / 0.9 (0.8, 1.1)
FreudenheimJL (1996)[55] / USA (America) / 297/311 / Recruitment: 1986-1991;
Age: 40-85 y;
FFQ (172 items);
Time frame: 2 year prior;
Menopause status: pre. / Vitamin C (mg/day)
dietary / 132-176 v.s. <=131 / 0.87(0.56, 1.36) / Age; education; age at first birth; age at menarche; first-degree relative with breast cancer; previous benign breast disease;BMI andkilocalories by residuals; quartile cutoffs shown are without adjustment for kilocalories.
177-223 v.s. <=131 / 0.70(0.44, 1.12)
≥224 v.s. <=131 / 0.53 (0.33, 0.86)
vitamin C (mg/day)
supplement / 1-47 v.s. 0 / 0.87 (0.52, 1.48)
48-263 v.s. 0 / 0.89(0.57, 1.39)
≥264 v.s. 0 / 0.98(0.62, 1.54)
α-Tocopherol (mg/day)
dietary / 7-8 v.s. <=6 / 0.69(0.44, 1.09)
9-10 v.s. <=6 / 0.84(0.54, 1.32)
≥11 v.s. <=6 / 0.55(0.34, 0.88)
α-Tocopherol (mg/day)
supplement / 1-29 v.s. 0 / 0.76(0.46, 1.27)
30 v.s. 0 / 1.04(0.67, 1.62)
≥31 v.s. 0 / 0.95(0.58, 1.55)
Gaudet MM (2004)[23] / USA (America) / 1463/1500 / Recruitment: 1996-1997;
Age: unspecified;
Self-administered
FFQ (100 items);
Time frame: a year prior;
Menopause status: pre- and post-. / Dietary
vitamin C
(mg/day) / 65.6–95.7 v.s. <65.6 / Pre: 1.04 (0.70, 1.54)
Post: 0.82 (0.61, 1.11) / Age and energy.
95.7–131.0 v.s. <65.6 / Pre: 0.91 (0.59, 1.39)
Post: 1.12 (0.84, 1.50)
131.1– 179.2 v.s. <65.6 / Pre: 1.05 (0.68, 1.62)
Post: 0.77 (0.57, 1.05)
179.3 v.s. <65.6 / Pre: 0.87 (0.56, 1.36)
Post: 0.83 (0.60, 1.14)
Dietary
vitamin E (α-TE/day) / 4.6–6.1 v.s. <4.6 / Pre: 1.03 (0.66, 1.60)
Post: 0.87 (0.65, 1.17)
6.1–7.8 v.s. <4.6 / Pre: 1.41 (0.88, 2.27)
Post: 0.87 (0.64, 1.20)
7.9–10.7 v.s. <4.6 / Pre: 1.27 (0.75, 2.14)
Post: 0.73 (0.52, 1.03)
10.7 v.s. <4.6 / Pre: 1.23 (0.70, 2.17)
Post: 0.87 (0.59,1.27)
Graham S (1991)[56] / USA (America) / 439/494 / Recruitment: 1986-1989;
Age: 41-85 y;
Questions (172 items);
Time frame: over 1-year period starting2 years before interview;
Menopause status: post. / Vitamin C (mg/day) / 129-173 v.s. <=128 / 0.84 (0.58, 1.23) / Age; education; age at first pregnancy; age at menarche; relative with breast cancer; benignbreast disease; number of pregnancies.
174-228 v.s. <=128 / 0.92 (0.63, 1.34)
>=229 v.s. <=128 / 0.62 (0.42, 0.91)
α-Tocopherol (mg/day) / 6-7 v.s. <=5 / 0.77 (0.53, 1.12)
8-10 v.s. <=5 / 0.78 (0.53, 1.13)
>=11 v.s. <=5 / 0.64 (0.44, 0.95)
Iscovich JM (1989)[57] / Argentina (America) / 150/150 / Recruitment: 1984-1985;
Age: all women;
FFQ (147 items);
Time frame: 5 year period up to 6 months prior to interview;
Menopause status: all. / Vitamin A
(per1000IU/day) / Comparison with neighbourhoodcontrols / 1.01(0.98, 1.05) / total caloric intake
Comparison with hospital controls / 1.01(0.97, 1.04)
Vitamin C
(per 100mg/day) / Comparison with neighbourhoodcontrols / 0.58(0.33, 1.02)
Comparison with hospital controls / 0.87(0.54, 1.41)
Longnecker MP (1997)[32] / USA (America) / 3543/9406 / Recruitment: 1988-1 991;
Age: less than 65y;
FFQ (-);
Time frame::2 years before;
Menopause status: all; / Vitamin A (IU/day)
dietary supplements / 0 v.s. never / 1.28 (1.05, 1.57) / Age; state; age at the first full-term pregnancy; parity;BMI; age at menarche; education; benign breast disease; ageat menopause; menopausal status; family history; and average lifetime alcohol intake.
0-<3000 v.s. never / 0.34 (0.17, 0.69)
3000-<6000 v.s. never / 0.94 (0.48, 1.83)
6000-<12000 v.s. never / 0.82 (0.54, 1.24)
>12000 v.s. never / 0.4 (0.15, 1.05)
Malin A S (2003)[22] / China (Asia) / 1459/1556 / Recruitment: 1996-1998;
Age: 25-64 y;
FFQ (76 items);
Time frame: 5-year period;
Menopause status: All (pre-and post-) / Vitamin A
(mg/day) / 80.3-123.9 v.s. <80.3 / All: 1.09 (0.85, 1.41)
Pre: 1.12 (0.81, 1.54)
Post: 1.07 (0.70, 1.62) / Age; education; family history of breast cancer; history of breast fibroadenoma; waist-to-hip ratio; menarche age; physical activity; ever had live birth; age at first live birth; menopausal status and total energy
123.9-173.5 v.s. <80.3 / All: 0.95 (0.73, 1.23)
Pre: 0.91 (0.65, 1.28)
Post: 0.99 (0.64, 1.53)
173.5-286.3 v.s. <80.3 / All: 1.02 (0.78, 1.33)
Pre: 0.92 (0.66, 1.28)
Post: 1.23 (0.78, 1.84)
>286.3 v.s. <80.3 / All: 1.00 (0.75, 1.32)
Pre: 0.86 (0.61, 1.21)
Post: 1.47 (0.89, 2.43)
Retinol
(mg/day) / 378.6-516.1 v.s.<378.6 / All: 1.23 (0.95, 1.58)
Pre: 0.90 (0.77, 1.45)
Post: 1.57 (1.03, 2.40)
516.1-1659 v.s. <378.6 / All: 1.00 (0.77, 1.28)
Pre: 0.90 (0.65, 1.24)
Post: 1.12 (0.73, 1.74)
1659-1867.2 v.s. <378.6 / All: 1.04 (0.80, 1.36)
Pre: 0.94 (0.66, 1.31)
Post: 1.19 (0.76, 1.86)
>1867.2 v.s. <378.6 / All: 1.08 (0.82, 1.42)
Pre: 0.92 (0.65, 1.29)
Post: 1.52 (0.94, 2.45)
Vitamin C
(mg/day) / 47.6-65.2 v.s. <47.6 / All: 0.84 (0.66, 1.08)
Pre: 0.83 (0.60, 1.13)
Post: 0.84 (0.55, 1.30)
65.2-82.4 v.s. <47.6 / All: 0.85 (0.66, 1.09)
Pre: 0.74 (0.54, 1.01)
Post: 1.05 (0.68, 1.64)
82.4-111.4 v.s. <47.6 / All: 0.89 (0.69, 1.15)
Pre: 0.90 (0.65, 1.24)
Post: 0.79 (0.51, 1.22)
>111.4 v.s. <47.6 / All: 0.88 (0.67, 1.15)
Pre: 0.87 (0.62, 1.21)
Post: 0.95 (0.61, 1.50)
Vitamin E (mg/day) / 9.4-12.1 v.s. <9.4 / All: 0.96 (0.74, 1.24)
Pre: 0.92 (0.67, 1.26)
Post: 1.03 (0.66, 1.63)
12.1-15.6 v.s. <9.4 / All: 1.19 (0.92, 1.54)
Pre: 1.03 (0.75, 1.41)
Post: 1.68 (1.07, 2.64)
15.6-19.9 v.s. <9.4 / All: 0.72 (0.54, 0.96)
Pre: 0.67 (0.47, 0.95)
Post: 0.85 (0.52, 1.38)
>19.9 v.s. <9.4 / All: 0.69 (0.50, 0.96)
Pre: 0.77 (0.52, 1.16)
Post: 0.65 (0.38, 1.11)
Mignone LI (2009)[25] / USA(America) / 5707/6389 / Recruitment: 1996-2001;
Age: 20-69 y;
Telephone interview;
Time frame: 5 years preceding diagnosis for case and corresponding date for control;
Menopause status: All (pre-and post-) / Vitamin A (µg/day) / 673.4-1076.5 v.s. <673.0 / All:0.90 (0.80–1.01
Pre:0.90 (0.75–1.08)
Post:0.92 (0.78–1.07) / Age; state; family history of breast cancer; age at first birth; alcohol intake; education; age at menarche;
history of benign breast disease; multivitamin use;BMI; smoking (status and pack years); hormone replacement therapy; parity;
menopausal status.
1077-1550.9 v.s. <673.0 / All: 0.94 (0.84, 1.06)
Pre: 0.87 (0.72, 1.04)
Post: 1.01 (0.86, 1.19)
1551.1-2309 v.s. <673.0 / All: 0.94 (0.84, 1.06)
Pre: 0.80 (0.67, 0.96)
Post: 1.06 (0.90, 1.24)
2309.6 v.s. <673.0 / All: 0.84 (0.74, 0.94)
Pre: 0.82 (0.68, 0.98)
Post: 0.87 (0.74, 1.03)
Moorman PG (2001)[17] / USA (America) / 861/790 / Recruitment: 1993-1996
Age: 20-74 y;
No FFQ;
Time frame: the past 5 years;
Menopause status: All. / Vitamin A
supplement / Any use / 1.59 (0.87, 2.89) / Age; age at menarche; age at first full-term pregnancy; menopausal status; lactation history; family history; BMI; WHR; education; alcohol use; smoking history; and fruit and vegetable intake
Vitamin C
supplement / Any use / 0.87 (0.64, 1.18)
1 year of use / 1.06 (0.66, 1.71)
1 to 3 years of use / 0.71 (0.48, 1.05)
3 years of use / 1.00 (0.62, 1.62)
Vitamin E
supplement / Any use / 0.92 (0.67, 1.28)
1 year of use / 1.54 (0.91, 2.59)
1 to 3 years of use / 0.71 (0.45, 1.10)
3 years of use / 0.78 (0.46, 1.35)
Potischman N (1999)[30] / USA (America) / 568/1451 / Recruitment: 1990-1992;
Age: 20-44y;
FFQ (100 items);
Time frame: a year prior;
Menopause status: pre. / Dietary Vitamin C
(mg/day) / 68-10 v.s. <68 / Chemotherapy :
1.10 (0.9, 1.4)
No Chemotherapy: 0.79 (0.6, 1.0) / Age at diagnosis; study site; ethnicity; education; age at first birth; alcohol intake; yearsof oral contraceptive use and smoking status.
103-152 v.s. <68 / Chemotherapy :
1.09 (0.9, 1.4)
No Chemotherapy: 0.88 (0.7, 1.2)
>=153 v.s. <68 / Chemotherapy :
1.37 (1.1, 1.7)
No Chemotherapy: 1.00 (0.8, 1.3)
Dietary
Vitamin E
(α-TE/day) / 6.3-8.3 v.s. <6.3 / Chemotherapy:
0.85 (0.7, 1.1)
No Chemotherapy:
0.79 (0.6, 1.0)
8.4-11.3 v.s. <6.3 / Chemotherapy:
1.03 (0.8, 1.3)
No Chemotherapy:
0.86 (0.7, 1.1)
>=11.4 v.s. <6.3 / Chemotherapy:
1.27 (1.0, 1.6)
No Chemotherapy:
1.11 (0.8, 1.4)
Dietary
Retinol
(μg/day) / 365-529 v.s. <365 / Chemotherapy:
1.09 (0.9, 1.4)
No Chemotherapy:
0.85 (0.7, 1.1)
530-750 v.s. <365 / Chemotherapy:
1.29 (1.0, 1.7)
No Chemotherapy:
0.86 (0.7, 1.1)
>=751 v.s. <365 / Chemotherapy:
1.53 (1.2, 2.0)
No Chemotherapy:
0.96 (0.7, 1.3)
Sup+diet
Vitamin C
(mg/day) / 95-165 v.s. <95 / 0.91 (0.7, 1.2)
166-389 v.s. <95 / 0.89 (0.7, 1.2)
>=390 v.s. <95 / 1.13 (0.9, 1.5)
Sup+diet
Vitamin E
(α-TE/day) / 8.2-16.4 v.s. <8.2 / 1.06 (0.8, 1.4)
16.5-31.1 v.s. <8.2 / 0.77 (0.6, 1.0)
>=31.2 v.s. <8.2 / 1.28 (1.0, 1.7)
Rohan TE (1988) [58] / Australia (Europe) / 451/451 / Recruitment: 1982-1984;
Age: 20-74 y;
FFQ (179 items);
Time frame: common;
Menopause status: all (pre- and post-). / Retinol (μg/day) / 249.6-376.4 v.s. <249.6 / All: 1.02 (0.67, 1.57) / No adjustment factors
376.4-551.1 v.s. <249.6 / All: 0.94 (0.62, 1.44)
551.1-1445.8 v.s. <249.6 / All: 0.95 (0.63, 1.44)
>=1445.8 v.s. <249.6 / All: 1.19 (0.78, 1.82)
310.5-642.5 v.s. <310.5 / pre: 1.55 (0.78, 3.05)
>=642.5 v.s. <310.5 / pre: 1.87 (0.92, 3.78)
247.3-368.9 v.s. <247.3 / post: 1.10 (0.63, 1.92)
368.9-533.3 v.s. <247.3 / post: 0.81 (0.46, 1.42)
533.3-1432.7 v.s. <247.3 / post: 0.92 (0.54, 1.56)
>=1432.7 v.s. <247.3 / post : 1.24 (0.73, 2.10)
Wang CX(2009)[19] / USA (America) / 1498/1559 / Recruitment: 1999-2004;
Age: 25-79 y;
computerized questionnaire (800 items);
Time frame: common;
Menopause status: all (pre- and post-). / Retinol / Q2 vs. Q1 / 0.82 (0.69, 0.97) / Age; education level; BMI; total METs per week for moderate and vigorous physical activity; total calorie intake per day; cigarette smoking; alcohol intake; center-age at menopause and HRT; race.
Q3 vs. Q1 / 0.96 (0.82, 1.14)
Q4 vs. Q1 / 0.88 (0.74, 1.05)
Total vitamin C / Q2 vs. Q1 / 1.16 (0.98, 1.38)
Q3 vs. Q1 / 1.09 (0.91, 1.30)
Q4 vs. Q1 / 1.01 (0.85, 1.21)
α-tocopherol / Q2 vs. Q1 / 0.86 (0.73, 1.02)
Q3 vs. Q1 / 0.90 (0.76, 1.07)
Q4 vs. Q1 / 0.87 (0.73, 1.03)
Nested Case Control study (2)
Nissen SB (2003)[13] / Denmark (Europe) / 424/394 / Recruitment: 1993-1997;
Age: 50-64 y;
FFQ (192 items);
Time frame: a year prior the study; Menopause status: post. / Vitamin A (μg/day) / <=800 v.s. 800-2000 / 1.57 (0.91, 2.70) / Two other vitamins; number of childbirths; age at first birth; history of benign breast disease surgery; school education; years of
use of HRT; alcohol intake and BMI.
2000-4000 v.s. 800-2000 / 1.34 (1.02, 1.76)
>4000 v.s. 800-2000 / 1.29 (0.81, 2.05)
Vitamin C
(μg/day) / <=60 v.s. 60-150 / 0.76 (0.44, 1.29)
150-300 v.s.60-150 / 1.15 (0.86, 1.55)
>300 v.s. 60-150 / 1.69 (1.12, 2.57)
Vitamin E (μg/day) / <=10 v.s. 10-15 / 0.98 (0.71, 1.36)
15-25 v.s. 10-15 / 0.96 (0.68, 1.36)
>25 v.s. 10-15 / 0.59 (0.37, 0.95)
Rohan TE (1993)[59] / Canada (America) / 519 / Recruitment: 1982-1987;
Age: 40-59 y;
Self-administered questionnaires (86 items);
Time frame: usual;
Menopause status: post. / Dietary
vitamin A
(IU/day) / 8545 v.s. 6133 / 1.22 (0.88, 1.70) / Age; energy intake; age at menarche; surgical menopause; age at first live birth; years of education; family history of breast
cancer and history of benign breast disease.
10793 v.s. 6133 / 0.85(0.59, 1.21)
14136 v.s. 6133 / 0.77(0.54, 1.11)
14136 v.s. 6133 / 0.80(0.55, 1.17)
Dietary
retinol
(IU/day) / 1884 v.s. 1158 / 0.92 (0.66, 1.29)
2678 v.s. 1158 / 0.80(0.56, 1.13)
4431 v.s. 1158 / 0.73(0.51, 1.04)
4431 v.s. 1158 / 0.83(0.58, 1.18)
Dietary
vitamin C (mg/day) / 137 v.s. 101 / 0.78 (0.56, 1.10)
172 v.s. 101 / 0.80(0.57, 1.13)
220 v.s. 101 / 0.89(0.63, 1.25)
220 v.s. 101 / 0.88(0.62, 1.26)
Dietary
vitamin E (mg/day) / 15 v.s. 12 / 0.91 (0.63, 1.33)
19 v.s. 12 / 0.83(0.57, 1.19)
25 v.s. 12 / 1.15(0.80, 1.67)
25 v.s. 12 / 0.96(0.63, 1.45)
Dietary
α-tocopherol
(mg/day) / 4 v.s. 3 / 0.94 (0.62, 1.41 )
74 v.s. 3 / 0.94(0.64, 1.39)
>74 v.s. 3 / 1.05(0.65, 1.70)
Supplement
vitamin A
(IU/day) / 5000 v.s. 0 / 1.10 (0.79, 1.54)
>5000 v.s. 0 / 0.70 (0.42, 1.15)
Supplement
vitamin C
(mg/day) / 250 v.s. 0 / 1.04 (0.78, 1.39)
>250 v.s. 0 / 1.46 (1.05, 2.01)
Supplement
vitamin E
(mg/day) / 4 v.s. 0 / 1.01 (0.69, 1.49)
>4 v.s. 0 / 1.00 (0.65, 1.54)
Supplement
α-tocopherol
(mg/day) / 3 v.s. 0 / 0.79 (0.47, 1.35)
>3 v.s. 0 / 1.20 (0.83, 1.75)
Case Cohort Study (1)
Verhoeven DTH(1997)[60] / The Netherlands (Europe) / 650/1598 / Recruitment: 1986-1990;
Age: 55-69 y;
FFQ (150 items);
Time frame: preceding the start of study for dietary intake, 5 year period before baseline for supplement;
Menopause status: post. / Retinol
(mg/day) / 0.341 v.s. 0.229 / 1.1 (0.78, 1.54) / Age; energy intake, alcohol intake; history of benign breast disease; maternal breast cancer; breast cancer in sister(s); age at menarche; age at menopause; age at first birth; parity.
0.424 v.s. 0.229 / 1.3 (0.92, 1.83)
0.535 v.s. 0.229 / 1.02 (0.7, 1.48)
0.766 v.s. 0.229 / 1.24 (0.83, 1.83)
Vitamin C
(mg/day) / 81.8 v.s. 58.6 / 0.71 (0.51, 0.98)
102.1 v.s. 58.6 / 0.76 (0.55, 1.05)
126.6 v.s. 58.6 / 0.68 (0.49, 0.95)
165.3 v.s. 58.6 / 0.77 (0.55, 1.08)
Vitamin E
(mg/day) / 8.49 v.s. 5.96 / 1.04 (0.74, 1.45)
11.28 v.s. 5.96 / 1.25 (0.89, 1.76)
14.36 v.s. 5.96 / 0.97 (0.68, 1.38)
19.82 v.s. 5.96 / 1.25 (0.85, 1.85)
Supplement
vitamin C
(mg/day) / Yes v.s. No / 1.06(0.79-1.43)
Cohort Studies (9)
Cho E (2003)[9] / USA (America) / 714/90655 / Recruitment: 1991-1999;
Age: 24-46 y;
FFQ (130 items);
Time frame: the past year before interview;
Menopause status: pre. / Total vitamin A
(IU/day) / 8,724 v.s. 5,639 / 1.02 (0.81, 1.29) / smoking status;BMI; height; age at menarche; oral contraceptive use; family history of breast cancer; history of benign breast disease; parity and age at first birth; menopausal status; intakes of
calories, animal fat, and alcohol.
11,466 v.s. 5,639 / 0.79 (0.62, 1.02)
14,884 v.s. 5,639 / 1.02 (0.81, 1.30)
21,916 v.s. 5,639 / 0.97 (0.76, 1.23)
Dietary
vitamin A
(IU/day) / 7,354 v.s. 4,895 / 0.92 (0.72, 1.16)
9,525 v.s. 4,895 / 0.86 (0.68, 1.10)
12,281 v.s. 4,895 / 0.96 (0.76, 1.21)
17,801 v.s. 4,895 / 0.92 (0.72, 1.17)
Total vitamin C
(mg/day) / 122 v.s. 80 / 0.97 (0.77, 1.23)
164 v.s. 80 / 1.00 (0.79, 1.27)
234 v.s. 80 / 0.96 (0.75, 1.23)
572 v.s. 80 / 0.96 (0.75, 1.21)
Dietary
vitamin C
(mg/day) / 97 v.s. 69 / 1.25 (0.97, 1.61)
122 v.s. 69 / 1.46 (1.14, 1.87)
150 v.s. 69 / 1.24 (0.96, 1.60)
200 v.s. 69 / 1.30 (1.00, 1.69)
Total vitamin E
(mg/day) / 8 v.s. 7 / 1.09 (0.85, 1.39)
10 v.s. 7 / 1.16 (0.91, 1.48)
15 v.s. 7 / 0.95 (0.73, 1.22)
59 v.s. 7 / 1.13 (0.89, 1.43)
Dietary
vitamin E
(mg/day) / 7 v.s. 6 / 1.15 (0.90, 1.48)
8 v.s. 6 / 1.17 (0.91, 1.49)
9 v.s. 6 / 1.12 (0.87, 1.43)
10 v.s. 6 / 1.17 (0.92, 1.50)
Cui Y (2008)[21] / USA (America) / 2879/81926 / Recruitment: 1993-1998;
Age: 50- 79 y;
FFQ (122 items);
Time frame: past 3 months;
Menopause status: post. / Total vitamin C (mg/day) / 97-<151 v.s. <97 / 1.02 (0.90, 1.16) / energy intake; ethnicity; age atbaseline; educational level; age at menarche; age at menopause; parity, age at first full-term pregnancy; oralcontraceptive use; postmenopausal hormone use; BMI; physical activity; alcohol drinking; dietary folate intake; tobacco smoking; hysterectomy; bilateraloophorectomy; history of benign breast disease; and family history of breast cancer
151-<240 v.s. <97 / 1.11 (0.97, 1.26)
240-<686 v.s. <97 / 1.07 (0.94, 1.22)
>=686 v.s. <97 / 1.18 (1.04, 1.34)
Dietary
vitamin C
(mg/day) / 67-<95 v.s. <67 / 0.97 (0.85, 1.10)
95-<123 v.s. <67 / 1.04 (0.91, 1.18)
123-<158 v.s. <67 / 1.06 (0.92, 1.21)
>=158 v.s. <67 / 1.06 (0.92, 1.22)
Supplement
vitamin C
(mg/day) / 0-<61 v.s. 0 / 1.03 (0.91, 1.16)
61-<347 v.s. 0 / 0.99 (0.88, 1.11)
347-<711 v.s. 0 / 1.04 (0.92, 1.16)
>=711 v.s. 0 / 1.16 (1.04, 1.30)
Totalvitamin E (mg/day) / 7.5-<22.2 v.s. <7.5 / 1.03 (0.91, 1.16)
22.2-<40.2 v.s. <7.5 / 0.98 (0.86, 1.11)
40.2-<419 v.s. <7.5 / 1.06 (0.94, 1.20)
>=419 v.s. <7.5 / 1.04 (0.92, 1.17)
Dietary
vitamin E
(mg/day) / 6.2-<7.1 v.s. <6.2 / 0.98 (0.86, 1.10)
7.1-<8.0 v.s. <6.2 / 1.03 (0.91, 1.17)
8.0-<9.4 v.s. <6.2 / 1.03 (0.91, 1.17)
>=9.4 v.s. <6.2 / 1.03 (0.91, 1.17)
Supplement vitamin E (mg/day) / >0-<30 v.s. 0 / 0.98 (0.87, 1.10)
30-<232 v.s. 0 / 1.05 (0.94, 1.18)
232-<424 v.s. 0 / 1.04 (0.92, 1.16)
>=424 v.s. 0 / 1.01 (0.90, 1.14)
Graham S (1992)[63] / USA (America) / 344/18586 / Recruitment: 1980-1987;
Age: >40 y;
FFQ (45 items);
Time frame: unspecified;
Menopause status: post. / Vitamin A (1000 IU/month) / 175-253 v.s. <174 / 0.93 (0.66, 1.30) / Age and education.
254-344 v.s. <174 / 0.96 (0.69, 1.34)
345-512 v.s. <174 / 1.07 (0.78, 1.49)
513-3333 v.s. <174 / 0.96 (0.68, 1.34)
Retinol (1000 IU/month) / 40-56 v.s. <39 / 0.91 (0.66, 1.25)
57-99 v.s. <39 / 0.91 (0.66, 1.27)
100-129 v.s. <39 / 0.9 (0.65, 1.26)
130-1310 v.s. <39 / 0.93 (0.67, 1.30)
Vitamin E
(mg/month) / 131-170 v.s. 30-130 / 0.87 (0.62-1.22)
171-212 v.s. 30-130 / 0.9 (0.64-1.26)
213-277 v.s. 30-130 / 1.11 (0.80-1.52)
278-2036 v.s. 30-130 / 0.86 (0.61-1.21)
Vitamin C
(100 mg/month) / 35-47 v.s. <34 / 0.73 (0.53-1.01)
48-60 v.s. <34 / 0.8 (0.58-1.10)
61-78 v.s. <34 / 0.73 (0.52-1.01)
79-498 v.s. <34 / 0.81 (0.59-1.12)
Hunter DJ (1993)[62] / USA (America) / 1439/88055 / Recruitment: 1980-1988;
Age: 30-55 y;
FFQ (121 items);
Time frame: unspecified;
Menopause status: all. / Vitamin C
(mg/day) / 93-131 v.s. <93 / 1.01 (0.85, 1.2) / Age; length of follow-up; energy intake; age at first birth; age at menarche; history of breast cancer in mother or a sister; BMI; menopausal status; alcohol intake; history of benign breast disease.
132-182 v.s. <93 / 1.02 (0.86, 1.2)
183-358 v.s. <93 / 1.03 (0.87, 1.22)
>=359 v.s. <93 / 1.03 (0.87, 1.21)
Vitamin E
(lU/day) / 3.9-4.9 v.s.<3.9 / 0.93 (0.79, 1.09)
5.0-7.3<3.9 / 0.93 (0.79, 1.1)
7.4-24<3.9 / 0.8 (0.67, 0.95)
>=24.1<3.9 / 0.9 (0.77, 1.06)
Vitamin A
(lU/day) / 6630-9579 v.s.<6630 / 0.89 (0.76, 1.04)
9580-12869 v.s.<6630 / 0.81( 0.69, 0.96)
12870 v.s.<6630 / 0.67 (0.57, 0.8)
>=17640 v.s.<6630 / 0.84 (0.71, 0.98)
Supplement
Vitamin C
(mg/day) / <400 v.s. 0 / 1.02 (0.77, 1.36)
400-700 v.s. 0 / 1.1 (0.9, 1.35)
750-1250 v.s. 0 / 0.84 (0.64, 1.11)
>=1300 v.s. 0 / 1.2 (0.75, 1.69)
Supplement
Vitamin E
(lU/day) / <100 v.s. 0 / 1.12 (0.77, 1.76)
100-250 v.s. 0 / 1.04 (0.73, 1.49)
300-500 v.s. 0 / 1.1 (0.88, 1.37)
>=600 v.s. 0 / 1.01 (0.69, 1.49)
Supplement
Vitamin A
(lU/day) / <8000 v.s. 0 / 0.84 (0.48, 1.45)
8000-12000 v.s. 0 / 1.23 (0.78, 1.95)
13000-22000 v.s. 0 / 1.63 (0.68, 3.95)
>=22000 v.s. 0 / 0.44 (0.14, 1.38)
Kushi LH (1996)[61] / USA (America) / 879/34387 / Recruitment: 1986-1992;
Age: 55-69y;
FFQ (127 items);
Time frame: 24-h dietary recall;
Menopause status: post / Total
Vitamin A
(lU/day) / 7,254-10,733 v.s. <7,254 / 0.99(0.78-1.25) / Age; energy intake; age at menarche; parity; age at menopause; age at first live birth; BMI at time of baseline questionnaire;BMI at age 18; family history of breast cancer; history of benign breastdisease; alcohol intake; and educational attainment.
10,734-14,582 v.s. <7,254 / 1.21 (0.97, 1.52)
14,583-20,342 v.s. <7254 / 1.25(1.00, 1.57)
>=20,343 v.s. <7254 / 0.88(0.68, 1.14)
Total
Retinol
(lU/day) / 1,233-2,983 v.s. <1,233 / 0.98(0.79, 1.23)
2,984-4,858 v.s. <1,233 / 0.89 (0.71, 1.12)
4,859-7,491 v.s. <1,233 / 1.04 (0.83, 1.30)
≥7,492 v.s. <1,233 / 1.01 (0.81, 1.26)
Total
Vitamin C
(lU/day) / 112-161 v.s.<112 / 1.02(0.82, 1.27)
162-227 v.s.<112 / 0.88(0.70, 1.12)
228-391 v.s.<112 / 1.09(0.87,1.36)
>=392 v.s.<112 / 0.88(0.70, 1.11)
Total
Vitamin E
(lU/day) / 5.67-7.79 v.s. <5.66 / 1.12 (0.89, 1.51)
7.80-12.18 v.s. <5.66 / 1.18 (0.92, 1.51)
12.19-35.65 v.s. <5.66 / 1.07 (0.84, 1.36)
>=35.66 v.s. <5.66 / 1.05 (0.83, 1.33)
Supplement
Vitamin A
(lU/day) / >0 -<5,000 v.s.0 / 0.88 (0.74, 1.06)
5,000-10,000 v.s.0 / 1.17 (0.93, 1.48)
>10,000 v.s.0 / 0.71 (0.47, 1.06)
Supplement
Retinol
(lU/day) / >0-<5,000 v.s.0 / 0.92(0.78, 1.10)
5,000-10,000 v.s.0 / 1.02(0.80, 1.30)
>10,000 v.s.0 / 0.77(0.49, 1.21)
Supplement
Vitamin C
(lU/day) / >0-<200 v.s.0 / 0.91 (0.77, 1.08)
200-500 v.s.0 / 0.94(0.73, 1.21)
501-1,000 v.s.0 / 0.86(0.65, 1.14)
>1,000 v.s.0 / 0.77 (0.50, 1.17)
Supplement
Vitamin E
(lU/day) / >0-<25 v.s. 0 / 0.97(0.79, 1.18)
25-100 / 0.94(0.72, 1.21)
100-250 / 1.06(0.72, 1.57)
>250 / 0.96 (0.76, 1.23)
Dietary
Vitamin A
(lU/day) / 6,189-8,773 v.s. <6,189 / 0.88(0.66, 1.18)
8,774-11,976 v.s. <6,189 / 1.15(0.87, 1.52)
11,977-16,775 v.s. <6,189 / 1.21 (0.92, 1.61)
>=16,776 v.s. <6,189 / 1.15(0.85, 1.56)
Dietary
Retinol
(lU/day) / 914-1,666 v.s. <914 / 1.02 (0.78, 1.33)
1,667-3,217 v.s. <914 / 0.84(0.63, 1.12)
3,218-4,568 v.s. <914 / 0.92(0.70, 1.22)
>=4,569 v.s. <914 / 1.04(0.78, 1.39)
Dietary
Vitamin C
(lU/day) / 87-120 v.s. <87 / 1.02(0.76, 1.37)
121-152 v.s. <87 / 0.95 (0.70, 1.29)
153-197 v.s. <87 / 0.96(0.70, 1.31)
>=198 v.s. <87 / 1.06(0.77, 1.47)
Dietary
Vitamin E
(lU/day) / 4.90-6.23 v.s. <4.89 / 0.89 (0.66, 1.20)
6.24-7.60 v.s. <4.89 / 1.09(0.81, 1.47)
7.61-9.64 v.s. <4.89 / 1.20(0.87, 1.65)
>=9.65 v.s. <4.89 / 1.08(0.74, 1.58)
Michels KB (2001)[15] / Sweden (Europe) / 1271/59036 / Recruitment: 1987-1990;
Age: 40–76 y;
FFQ (67 items );
Time frame: past 6 months
Menopause status: all. / Vitamin E (mg/day) / 9.3 v.s.3.8 / 0.83 (0.60, 1.14) / age; family history of breast cancer; height; BMI; parity; education; age atfirst birth; total caloric intake and intake of alcohol, fiber and monounsaturated fatty acids.
Retinol
(mg/day) / 1.51v.s. 0.52 / 1.00 (0.83, 1.20)
Nagel G (2010)[27] / 10 European
countries (Europe) / 6478/288776 / Recruitment: 1992-2000;
Age: 35–70 y;
FFQ (260 items);
Time frame: past 12 months;
Menopause status: pre- + post-. / Vitamin C (mg/day) / Q2 vs. Q 1 / Pre: 1.06 (0.89, 1.27)
Post: 0.91 (0.82, 1.02) / Energy from protein and carbohydrates; education; monounsaturated fatty acids; polyunsaturated fatty acids; alcohol intake; weight; height; age at menarche; parity; age at first full-term pregnancy; use of hormone therapy at recruitment; smoking status; physical activity index
Q 3 vs. Q 1 / Pre:1.17 (0.99, 1.40)
Post: 0.99 (0.88, 1.10)
Q 4 vs. Q 1 / Pre: 1.07 (0.89, 1.28)
Post: 1.01 (0.91, 1.13)
Q 5 vs. Q 1 / Pre: 1.12 (0.92, 1.36)
Post: 0.98 (0.87, 1.11)
Vitamin E (mg/day) / Q2 vs. Q 1 / Pre: 1.00 (0.83, 1.21)
Post: 0.92(0.82, 1.02)
Q 3 vs. Q 1 / Pre: 1.00 (0.82, 1.22)
Post: 0.97 (0.85, 1.90)
Q 4 vs. Q 1 / Pre: 1.04 (0.83, 1.29)
Post: 0.96 (0.83, 1.10)
Q 5 vs. Q 1 / Pre: 1.11 (0.84, 1.46)
Post: 0.92 (0.77, 1.11)
Shibata A (1992)[64] / USA (America) / 219/10464 / Recruitment: 1981-1989;
Age: unspecified;
FFQ (59 items);
Time frame: usual;
Menopause status: all. / Dietary
vitamin C (mg/day) / 188 v.s. 114 / 0.75 (0.54, 1.04) / Age and smoking.
274 v.s. 114 / 0.86 (0.63, 1.18)
Supplement vitamin A (mg/day) / 10000 v.s. 0 / 0.94 (0.72, 1.23)
Supplement vitamin C (mg/day) / 500 v.s. 0 / 0.93 (0.71, 1.23)
Supplement vitamin E (mg/day) / 200 v.s. 0 / 0.89 (0.68, 1.16)
Zhang S (1999)[8] / USA (America) / 2697/83234 / Recruitment: 1976-1994;
Age: 33–55 y;
FFQ (126 items);
Time frame: usual;
Menopause status: all （pre-+post-） / Total vitamin A
(IU/day) / 21379 v.s. 5783 / Pre: 0.87 (0.70, 1.09)
Post: (1.03 0.89, 1.20) / Age; length of follow-up; total energy intake; parity; age atfirst birth; age at menarche; history of breast cancer in mother or a sister , history of benign breast
Disease; alcohol intake;BMI at age 18 years; weight change from age 18 years; height in inches; menopausal status; age at menopause; andpostmenopausal hormone use.
Dietary vitamin A (IU/day) / 17073 v.s. 5293 / Pre: 0.82 (0.65, 1.04)
Post: 1.03 (0.89, 1.19)
Total retinol (IU/day) / 9366 v.s. 1021 / Pre: 0.78(0.62, 0.99)
Post: 0.95(0.83, 1.10)
Dietary retinol (IU/day) / 4391 v.s. 800 / Pre: 0.88(0.70, 1.10)
Post: 1.05(0.91, 1.21)
Supplement
vitamin A
(IU/day) / <8000 v.s. never / 0.93 (0.61, 1.42)
8000–12000 v.s. never / 1.21 (0.84, 1.72)
13 000–22000 v.s. never / 1.11 (0.46, 2.67)
>=23000 v.s. never / 0.49 (0.20, 1.18)
Total vitamin C
(IU/day) / 710 v.s. 83 / Pre: 1.01 (0.81, 1.26)
Post: 0.99 (0.85, 1.14)
Dietary vitamin C (IU/day) / 205 v.s. 70 / Pre: 1.01 (0.81, 1.26)
Post: 1.06 (0.91, 1.22)
Supplement
vitamin C
IU/day / <400 v.s. never / 0.96 (0.73, 1.25)
400–700 v.s. never / 1.08 (0.93, 1.27)
750–1250 v.s. never / 1.02 (0.85, 1.23)
>=1300 v.s. never / 1.04 (0.77, 1.42)
Total vitamin E
(IU/day) / 251 v.s. 5 / Pre: 1.22 (0.98, 1.52)
Post: 0.84 (0.72, 0.96)
Dietary vitamin E (IU/day) / 10 v.s. 5 / Pre: 0.81 (0.64, 1.02)
Post: 0.96 (0.83, 1.11)
Supplement
vitamin E
IU/day / <100 v.s. never / 0.98 (0.64, 1.49)
100–250 v.s. never / 1.07 (0.83, 1.37)
300–500 v.s. never / 1.19 (1.04, 1.37)
>=600 v.s. never / 0.92 (0.70, 1.21)
RCT studies (3)
Lee IM (2005)[65] / USA (America) / 19937/19939 / Recruitment: 1992-2004;
Age: ≥45y;
2x2 factorial trial;
Menopause status: post. / vitamin E / 600 IU every other day/Placebo / 1.00 (0.90, 1.12) / No adjustment factors
Lin J (2009)[67] / USA (mixed) / 3824/3803 / Recruitment: 1992-1995;
Age: >=40y;
2x2x2 factorial trial;
Menopause status: post / vitamin C / 500 mg daily/Placebo / 1.11 (0.87, 1.41) / No adjustment factors
vitamin E / 600 IU every other day/Placebo / 0.98 (0.77 to 1.25)
Lonn E (2005)[66] / Canada (mixed) / 19/26 / Recruitment: 1993-2003;
Age: >=55 y;
2x2 factorial trial;
Menopause status: post / vitamin E / 400 IU daily/Placebo / 0.86 (0.50, 1.47) / No adjustment factors

*Time frame for dietary assessment.