Supplemental Table 1 Basic information of studies entered the meta-analysis. Reference Country ( continent of study) Cases/controls or cohort size Baseline information Vitamins Plasma/serum Vitamins OR/ RR (95%CI) or mean ± SD Adjustment factors Case Control Studies-Hospital Based (26) Abiaka C (2001) Aghvami T (2006) Kuwait (Asia) Iran (Asia) Al-Saleh I (2002) Saudi Arabia (Asia) Badid N (2010) Algeria (Africa) 28/58 Amiri and Adan Hospitals; Recruitment: no reported; Age: unspecified; Menopause status: all; Unspecified breast cancer. 50/50 Imam Khomeini Hospital; Recruitment: no reported; Age: 30-68 years; Menopause status: all; Stage I, II and III breast cancer. 108/134 King Faisal specialiat Hospital; Recruitment: unspecified; Age: 22-81 years; Menopause status: all; Unspecified breast cancer. 38/50 Telmcen Hospital; private clinic for surgery; Recruitment: 2006-2007; — α-tocopherol (μmol/l) breast cancer v.s. control (mean SE) Vitamin C (mg/dl) breast cancer v.s. control Vitamin E (μg/ml) breast cancer v.s. control α-tocopherol (μg/l) breast cancer v.s. control Vitamin A (μmol/l) Vitamin C breast cancer v.s. control 16.8 1.00 v.s. 17.7 0.9 1.76 0.47 v.s. 1.57 0.45 all 0.89 0.36 v.s. 0.83 0.26 pre 0.78 0.41 v.s. 0.99 0.34 post 12.28 3.06 v.s. 13.56 3.23 all 11.47 2.76 v.s. 12.19 2.05 pre 13.24 3.17 v.s. 15.98 3.53 post 2.82 3.06 v.s. 4.64 3.08 14.58 2.37 v.s. 16.70 2.45 15.00 3.15 v.s. 38.58 6.43 — Canada (America) Basu TK (1989) 30/30 Ching S (2002) Australia (Australia) 153/150 Chitkara N (1996) India (Asia) 75/50 Argentina (Europe) 15/11 De Cavanagh (2002) EMV Age: 35-45 years; Overweight women; Menopause status: pre; Stage II and III breast cancer. National Cancer Institute; Recruitment: unspecified; Age: mean: 55.2 years; Menopause status: all; advanced breast cancer. Sir Charles Gairdner Hospital; Recruitment: 1992-1994; Age: 30-84 years; Menopause status: pre and post; Stage T1, N0, N1 or N2 without metastasis breast cancer Recruitment: unspecified; Age: 20-70 years; Menopause status: all; Unspecified breast cancer The British and I. Iriarte Hospital; Recruitment: Unspecified; Age: 41-55 years; Menopause status: pre; (μmol/l) Vitamin E (μmol/l) 13.73 1.38 v.s. 24.55 2.13 Vitamin A (μg/dl) 68.0 5.3 v.s. 74.7 6.0 Vitamin E (mg/dl) breast cancer v.s. control 0.81 0.08 v.s. 0.91 0.08 Retinol (μmol/l) ≥2.5 v.s. ≤1.9 0.53 (0.28, 1.01) Vitamin E (μg/ml) breast cancer v.s. control 1.70 0.15 v.s. 4.54 0.17 breast cancer v.s. control 4.7 1.4 v.s. 20.8 2.2 α-tocopherol (μmol/l) — Age at menarche, parity, alcohol intake and total fat intake Gerber M (1988) Gerber M (1989) Italy and France (Europe) France (Europe) 210/209 Milan 96/105 Montpellier 120/109 Gerber M (1991) France (Europe) 48/50 Hou MF (1998) Taiwan 106/40 Stage IIIA, IIIB, and IV or with ductal breast cancer The French case-control study; Recruitment: 1982-1986; Age: 25-65 years; Menopause status: all; Stage T1, N0, N1 or N2 without metastasis breast cancer The French case-control study; Recruitment: 1982-1986; Age: 25-65 years; Menopause status: pre and post Stage T1, N0, N1 or N2 without metastasis breast cancer The last cases and controls in French case-control study; in Languedoc-Roussillon; Recruitment: unspecified; Age: 25-65 years; Menopause status: all; Stage T1, N0, N1 or N2 without metastasis breast cancer. Kaohsiung Medical College Vitamin E (mg/l) breast cancer v.s. control 12.0 3.13 v.s. 10.9 2.67 Milan 12.40 2.9 v.s. 11.4 2.7 Montpellier Retinol (μg/l) breast cancer v.s. control 549 127.2 v.s. 587 133.8 Montpellier — — Vitamin E (mg/l) breast cancer v.s. control 12.50 3.6 v.s. 10.3 1.9 pre 13.80 3.1 v.s. 21.3 2.6 post — Vitamin C (mg/l) breast cancer v.s. control 7.82 3.89 v.s. 6.97 3.86 Vitamin A breast cancer 140.50 65.70 v.s. 144.00 30.30 (Asia) Ito Y (1999) India (Asia) 206/150 Hospital in Taiwan; Recruitment: 1995-1996; Age: 30-70 years; Menopause status: all; All stage breast cancer Cancer Institute (W.I.A.); Recruitment: 1992-1993; Age: 22-80 years; Menopause status: all; pre- and postmenopausal; All stage breast cancer (μg/dl) v.s. control 1.66 0.54 v.s. 1.50 0.65 Retinol (μmol/l) α-tocopherol (μmol/l) α-tocopherol (μg/ml) breast cancer v.s. control breast cancer v.s. control (mean SEM) Kim MK (2001) Korea (Asia) 160/229 16.75 5.29 v.s. 15.41 5.20 7.63 0.42 v.s. 11.0 0.73 all 6.95 0.47 v.s. 10.3 0.56 pre ≥13.50 v.s. <4.95 0.41 (0.18-0.93) 8.90 0.81 v.s. 14.8 3.37 post Asian Medical center; Recruitment: 1994-1995; Age: less than 80 years; Menopause status: all Unspecified breast cancer. ≥15.0 v.s. <5.00 breast cancer v.s. control 0.13 (0.03-0.66) 49.0 4.10 v.s. 64.6 1.95 48.0 6.11 v.s. 64.2 2.00 51.0 2.86 v.s. 66.5 6.13 Retinol (μg/dl) — ≥0.20 v.s. <0.08 1.03 (0.32-3.33) ≥1.57 v.s. <0.89 0.14 (0.03-0.58) Age; BMI; smoking; alcohol drinking; Kim MK (2002) Kim MK (2010) London SJ (1992) Korea (Asia) Korea (Asia) USA (America) 92/122 376/304 377/403 Asian Medical center; Recruitment: 1993-1994; Age: less than 80 years; Menopause status: all Unspecified breast cancer. Age: 58-69 years; Menopause status: post; Stage I or II breast cancer. 18.1 12.4 v.s. 27.2 18.1 ≥31.4 v.s. <17 0.32 (0.09-1.19) Retinol (μg/dl) 79.7-134 v.s. 23.8-49.1 0.145 (0.077-0.271) α-tocopherol (μg/dl) γ-tocopherol (μg/dl) 1554-4063 v.s. 335-946 410-964 v.s. 46.3-213 Retinol (μmol/l) 2.7 v.s. 1.47 1.0 (0.6-1.7) 48 v.s. 22 0.8 (0.5-1.2) α-tocopherol (μmol/l) Asian Medical center; Recruitment: 2006-2007; Age: less than 80 years; Menopause status: all; All stage breast cancer. Five teaching hospitals Boston; Recruitment: 1986-1988; breast cancer v.s. control 2.342 (1.345-4.078) 1.908 (1.107-3.287) in α-tocopherol (μmol/l) Age; BMI; weight; alcohol; smoking; menopausal status; age at 1st full-term pregnancy; serum low-density lipoprotein cholesterol; fruit and vegetable consumption Age; BMI; menopause; parity; oral contraceptive; smoking status; alcohol consumption status Age; alcohol intake; age at first birth; family history of breast cancer; age at menopause; age at menarche; body weight; prior history of BBD; serum lipid Marubini E (1988) Potischman N (1990) Ramaswamy G (1996) Italy (Europe) USA (America) India (Asia) 210/209 81/101 100/50 National Tumor Institute of Milan; Recruitment: 1982-1985; Age: 30-65 years; Menopause status: all Stage I-II breast cancer Roswell Park Memorial Institute; Two private surgeons; Recruitment: 1985-1986; Age: 30-80 years; Menopause status: all; All stage breast cancer. Kidwai Memorial Institute of Oncology in Bangalore; Recruitment: unspecified; Age: 30-65 years; Menopause status: all; All stage breast cancer. Retinol (μg/l) breast cancer v.s. control 556.78 133.79 v.s. 530.06 144.36 Fifth v.s. lowest 2.0 (1.0-4.0) breast cancer v.s. control 1.95 0.62 v.s. 1.93 0.44 Q4 v.s. Q1 0.94 (0.27-3.23) Retinol (μmol/l) 38.10 13.1 v.s. 39.8 12.2 stage I Vitamin A (μg/dl) breast cancer v.s. control 30.60 11.5 v.s. 39.8 12.2 stage II 26.40 12.4 v.s. 39.8 12.2 stage III 26.10 11.8 v.s. 39.8 12.2 stage Age; age at menarche; age at first birth; parity; age at menopause; Quetelet index; family history of breast cancer; education; cholesterol; triglyceride blood level Age; age at first birth; family history; age at menarche; Quetelet index; parity; age at menopause; income; marital status; lipids include cholesterol and triglyceride; — IV 1.00 0.3 v.s. 1.98 0.5 stage I Vitamin C (mg/dl) breast cancer v.s. control 0.80 0.2 v.s. 1.98 0.5 stage II 0.40 0.1 v.s. 1.98 0.5 stage III 0.30 0.1 v.s. 1.98 0.5 stage IV Ray G (2001) Schrijver J (1987) Shah FD (2009) Simon MS (2000) India (Africa) The Netherlands (Europe) India (Asia) USA (America) 54/42 11/16 125/70 27/29 Sucheta Kripalini Hospital; Recruitment: unspecified; Age: 24-70 years; Menopause status: all (pre- and post-) Stage II, III and IV breast cancer Recruitment: July-December 1982; Age: 41-80 years; Menopause status: post; Advanced breast cancer. GCRI; Recruitment: unspecified; Age: 25-82 years; Menopause status: all; Stage II, III and IV breast cancer. A pilot case-control study; Recruitment: July, 15, 1994December, 1, 1994; — Vitamin A (μmol/l) Mean SEM Vitamin C (μmol/l) Vitamin E (μmol/l) Vitamin A (μmol/l) breast cancer v.s. control 1.94 0.06 v.s. 1.88 0.07 breast cancer v.s. control breast cancer v.s. control Breast cancer v.s. control 155.0 5.67 v.s. 186.3 9.08 α-tocopherol (nmol/l) Breast cancer v.s. control 23.8 6.8 v.s. 30.3 6.5 Vitamin A (mg/l) Vitamin E (mg/l) Vitamin C (mg/l) Breast cancer v.s. control Breast cancer v.s. control Breast cancer v.s. control 1.41 0.08 v.s. 0.53 0.04 Retinol (μmol/l) breast cancer v.s. control 24.87 0.72 v.s. 28.3 0.05 1.00 0.41 v.s. 1.79 0.38 12.6 1.03 v.s. 15.1 1.22 1.90 0.10 v.s. 3.54 0.36 2.37 0.73 v.s. 1.98 0.49 African-American 2.16 0.61 v.s. 2.05 0.61 — Age: mean: 59 years; Menopause status: all; Invasive breast cancer. Caucasian α-tocopherol (μmol/l) γ-tocopherol (μmol/l) Torun M (1995) Torun M (1995) Turkey (Asia) Turkey (Asia) 100/70 25/156 Unspecified Case-control; Recruitment: unspecified; Age: unspecified; Menopause status: all (pre- and post-); Unspecified breast cancer Unspecified Case-control; Recruitment: unspecified; Age: unspecified; Menopause status: all; Unspecified breast cancer ≤1.59 v.s. ≥ 2.60 0.87 (0.14, 5.72) breast cancer v.s. control 31.20 15.52 v.s. 23.47 7.66 African-American 34.98 15.99 v.s. 38.76 16.45 Caucasian ≤20.52 v.s. ≥35.00 0.76 (0.10, 5.75) breast cancer v.s. control 5.74 2.54 v.s. 4.90 3.25 African-American 5.09 3.59 v.s. 3.76 3.99 Caucasian ≤2.12 v.s. ≥ 7.57 0.31 (0.04, 1.93) 0.44 0.21 v.s. 1.108 0.27 all Vitamin E (mg/100ml) breast cancer v.s. control — 0.43 0.19 v.s. 1.11 0.24 pre 0.45 0.11 v.s. 1.11 0.31 post — Vitamin C (mg/dl) breast cancer v.s. control 0.50 0.43 v.s. 0.80 0.35 Case-Control Studies-Population Based (2) Suzana S (2008) Zaroukian S (2005) Malaysia (Asia) Canada (America) 57/139 223/85 Klang Valley and Selangor, Malaysia; Recruitment: unspecified; Age: 30-66 y; Menopause status: all; Stage I-III breast cancer. Four teaching hospitals CHUM; Recruitment: 1989-1993; Age: 35-79 years; Menopause status: all; Unspecified breast cancer. of Vitamin E (mg/dl) Vitamin A (μg/l) Retinol (μmol/l) Tocopherol (μmol/l) breast cancer v.s. control 2.8-3.18 v.s. <2.5 breast cancer v.s. control >564 v.s.<284.3 breast cancer v.s. control 377.6 417 v.s. 431.5 264.2 Q3 v.s. Q1 0.67 (0.35-1.28) breast cancer v.s. control 18. 35 6.90 v.s. 18.59 5.77 Q3 v.s. Q1 0.85 (0.45-1.59) ≥0.73 v.s. <0.52 1.17 (0.77-1.78) ≥13.22 v.s. <9.36 1.07 (0.67-1.71) ≥10.32 v.s. <7.11 1.15 (0.72-1.85) 1.45-1.89 v.s. <1.45 1.01 (0.68-1.46) 3.3 3.9 v.s. 4.0 2.7 2.76 (1.43-5.33) No adjustment factors 2.32 (1.18-4.57) 1.86 0.87 v.s. 1.97 0.69 Age; age at first full term pregnancy; history of cancer in first-degree relatives; Nested case-control studies (13) Retinol (mg/l) Dorjgochoo T (2009) China (Asia) 365/726 SWHS; Recruitment: 1997–2000; Age: 40-70 years; Menopause status: all (pre- and post-); Unspecified breast cancer. Total tocopherols (mg/l) α-tocopherols (mg/l) β/γ -tocopherols (mg/l) Age at entry; education; occupation; age at menarche; age at 1st live birth; waist to hips ratio; exercised regularly in past 5 years; ever smoke; menopausal status; history of breast Dorgan JF (1998) Epplein M (2009) USA (America) USA (mixed) 105/203 286/535 US National Cancer Institute; Recruitment: 1977-1987; Age: median: 61.6 years; Menopause status: all; All stage breast cancer. Multiethnic Cohort study; Recruitment: 2001–2006; Age: 45-75 years; Menopause status: post; Unspecified breast cancer. Retinol (μmol/l) 2.31-3.32 v.s. <1.67 0.9 (0.4-2.0) α-tocopherol (μmol/l) 31.33-107.69 v.s. <21.59 1.2 (0.5-2.8) Retinol (ng/ml) Total-tocopherol s (ng/ml) α-tocopherols (ng/ml) ≥1188.0 v.s. ≤842.6 ≥23282.4 v.s. ≤14413.3 ≥21829.9 v.s. ≤11828.1 1.13 (0.73-1.76) 0.86 (0.56-1.31) 0.80 (0.52-1.24) fibroadenoma; 1st degree family history cancer; total energy; vegetables; fruits; red meat and fish; regular tea consumption, batch for assays; other plasma lipophilic antioxidants Age; BMI; benign breast disease diagnosis during prior 2 years; month and year of blood collection; total serum cholesterol concentration, packs of cigarettes smoked/day. BMI; alcohol use; age at menarche; age at menopause; age at first birth; number of full-term pregancies; age at blood draw Hulten K (2001) Sweden (Europe) 201/390 Recruitment: VIP, MONICA, MSP; Age: VIP+MONICA median: 52 years, MSP median: 59 years; Menopause status: all; Unspecified breast cancer. β/γ -tocopherols (ng/ml) ≥2175.3 v.s. ≤619.0 1.40 (0.86-2.27) Retinol (μmol/l) Forth v.s. lowest 1.0 (0.6-1.8) α-tocopherol (μmol/l) Forth v.s. lowest 1.3 (0.6-2.7) Retinol (μg/ml) Kabat GC (2009) USA (America) 190/5260 Women’s Health Initiative clinical trials (WHI); Recruitment: 1993-1998; Age: 50-79 years; Menopause status: post; In situ and invasive breast cancer. α-tocopherol (μg/ml) γ-tocopherol (μg/ml) Breast cancer v.s. control ≥0.65 v.s. <0.53 Breast cancer v.s. control ≥17.23 v.s. <12.36 Breast cancer v.s. control 16.79 7.38 v.s. 16.60 7.72 ≥2.55 v.s. <1.30 1.26 (0.85-1.88) 0.61 0.15 v.s. 0.60 0.16 1.00 (0.68-1.48) 0.92 (0.62-1.36) 2.16 1.28 v.s. 2.11 1.43 BMI; plasma total cholesterol and triglycerides Age; education; ethnicity; BMI; oral contraceptive use; hormone therapy; age at menarche; age at first birth; age menopause; alcohol; family history of breast cancer; history of breast biopsy; physical activity; energy intake; randomization status in hormone therapy; Knekt P (1988) Finland (Europe) 67/123 Knekt P (1990) Finland (Europe) 52/93 Maillard V (2010) French (European) 366/720 Social Insurance Institution’s Mobile Clinic Health Examination Survey; Recruitment: 1968-1972; Age: 15-99 years; Menopause status: all; unspecified breast cancer. Social Insurance Institution’s Mobile Clinic Health Examination Survey; Recruitment: 1968-1977; Age: 15-99 years; Menopause status: all; unspecified breast cancer. E3N-EPIC study; Recruitment: 1989-1991; Age: 40-65 years; Menopause status: all Invasive breast cancer calcium plus vitamin D; and dietary modification trials. Smoking and cholesterol Vitamin E (mg/l) >12.51 v.s. ≤7.90 0.88 (0.32-2.39) Retinol (μg /l) >710.0 v.s. ≤490.0 1.20 (0.50-2.70) No adjustment Breast cancer v.s. control The fifth v.s. lowest Breast cancer v.s. control The fifth v.s. lowest 1.87 0.4 v.s. 1.89 0.4 Breast cancer 1.87 0.4 v.s. 1.89 0.4 Alcohol; Height; Education level; menopausal hormone use; age at first birth and parity; family history of breast cancer; history of benign breast disease. Retinol (μmol/l) α-tocopherol (μmol/l) γ-tocopherol 0.85 (0.53-1.35) 1.87 0.4 v.s. 1.89 0.4 0.70 (0.44-1.13) Russell MJ (1988) Sato R (2002) England (Europe) USA (America) 30/288 244/244 (1974 cohort) 115/115 (1989 cohort) Volunteer women in Guernsey; Recruitment: 1977-1985; Age: 26-88 years; Menopause status: all; Unspecified breast cancer. Washington County; Recruitment: 1974 and 1989 cohort; Age: 43-70 years; Menopause status: all; In situ and invasive breast cancer. (μmol/l) v.s. control total-tocopherol (μmol/l) Vitamin A (μg/l) The fifth v.s. lowest Breast cancer v.s. control The fifth v.s. lowest breast cancer v.s. control Vitamin E (mg/l) breast cancer v.s. control Retinol (μg/dl) 1974 cohort 1989 cohort ≥73.0 v.s. <46.2 ≥73.8 v.s. <50.4 α-tocopherol (mg/dl) 1974 cohort ≥1.40 v.s. <0.91 1989 cohort γ-tocopherol (mg/dl) 1974 cohort 1989 cohort ≥1.65 v.s. <0.99 ≥0.32 v.s. <0.15 ≥0.34 v.s. <0.13 0.94 (0.59-1.48) 1.87 0.4 v.s. 1.89 0.4 0.68 (0.41-1.10) 549 128 v.s. 533 131 6.5 2.4 v.s. 6.2 2.1 0.97 (0.53-1.80) 1.03 (0.40-2.64) 0.94 (0.52-1.73) 0.67 (0.28-1.62) 0.70 (0.40-1.23) 0.80 (0.33-1.93) — Tamimi RM (2005) Toniolo P (2001) USA (America) USA 969/969 270/270 “—”: T test, no adjustment reported. Nurses’ Health Study; Recruitment: 1989–1990; Age: 43-70 years; Menopause status: all; In situ and invasive breast cancer. Women’s Health Study; Recruitment: 1985-1994; Age: 35-65 years; Menopause status: all; All stage breast cancer. α-tocopherol (μmol/l) 46.94 v.s. 16.42 0.79 (0.57-1.08) γ-tocopherol (μmol/l) 7.72 v.s. 1.90 0.96 (0.71-1.30) breast cancer v.s. control 56.9 13.5 v.s. 56.0 13.8 Low v.s. high 0.78 (0.45-1.35) Retinol (μg/dl) Age; menopause postmenopausal hormone use;month; time of day; fasting at blood collection; age at menopause; BMI at 18; weight gain since 18y; age at menarche; history of benign breast disease; history of breast cancer in a mother or sister; age at first birth/parity; alcohol consumption Age at first full-term pregnancy; family history of breast cancer; history of benign breast disease and total cholesterol