Table 3.

Hazard Ratio of Total Invasive Cancer and Breast Cancer according to Randomized Folic Acid/Vitamin B₆/Vitamin B₁₂ Treatment, by Baseline Characteristics of Participants

	Total Invasive Cancera					Breast Cancer
	Active Group	Placebo Group	Hazard Ratio (95% Confidence Interval)	P Value	P for Interaction	Active Group	Placebo Group	Hazard Ratio (95% Confidence Interval)	P Value	P for Interaction
	no. of cases					no. of cases
Overall	187	192	0.97 (0.79–1.18)	.75		70	84	0.83 (0.60–1.14)	.24
Age, y					.02					.05
40–54	22	16	1.42 (0.75–2.71)	.28		12	8	1.56 (0.64–3.81)	.33
55–64	77	59	1.26 (0.90–1.76)	.19		27	26	1.00 (0.58–1.72)	>.99
≥65	88	117	0.75 (0.57–0.99)	.05		31	50	0.62 (0.40–0.98)	.04
CVD health history					.79					.26
Prior CVDb	123	123	0.99 (0.77–1.27)	.91		49	51	0.95 (0.64–1.40)	.78
≥3 risk factorsc	64	69	0.93 (0.66–1.31)	.68		21	33	0.65 (0.37–1.12)	.12
History of cancer within the past ten yearsd				.76					.91
Yes	18	18	1.09 (0.57–2.10)	.80		5	6	0.87 (0.27–2.87)	.83
No	169	174	0.96 (0.78–1.19)	.70		65	78	0.82 (0.59–1.14)	.24
Smoking status					.50					.82
Current	27	28	1.11 (0.66–1.89)	.69		7	7	1.18 (0.41–3.38)	.76
Past	86	99	0.86 (0.65–1.15)	.31		35	42	0.83 (0.53–1.30)	.41
Never	74	65	1.10 (0.79–1.53)	.59		28	35	0.77 (0.47–1.27)	.30
Alcohol use in past year, g/d				>.99					.51
0	99	114	0.87 (0.66–1.13)	.29		35	52	0.67 (0.44–1.03)	.07
>0 – < 15	77	63	1.19 (0.85–1.66)	.31		32	24	1.30 (0.76–2.20)	.34
≥ 15	11	15	0.88 (0.40–1.92)	.75		3	8	0.44 (0.12–1.67)	.23
Body mass indexe					.18					.88
<25	39	44	0.80 (0.52–1.24)	.32		12	13	0.82 (0.37–1.79)	.61
25–<30	51	62	0.88 (0.61–1.28)	.51		25	30	0.89 (0.52–1.51)	.66
≥ 30	97	86	1.11 (0.83–1.48)	.48		33	41	0.79 (0.50–1.25)	.32
Menopausal status					.85					.20
Premenopausal	5	4	1.28 (0.34–4.86)	.71		3	2	1.32 (0.22–8.02)	.76
Uncertain	6	4	1.31 (0.37–4.70)	.68		2	0	--
Postmenopausal	176	184	0.95 (0.77–1.17)	.64		65	82	0.79 (0.57–1.09)	.15
Postmenopausal hormone usef				.64					.69
Current	82	95	0.87 (0.65–1.17)	.35		32	46	0.69 (0.44–1.09)	.11
Past	35	33	1.08 (0.67–1.74)	.74		15	16	0.97 (0.48–1.96)	.92
Never	59	56	1.06 (0.74–1.54)	.74		18	20	0.91 (0.48–1.73)	.77
Physical activity, kcal/wk					.60					.97
<1000	130	131	1.01 (0.79–1.28)	.95		45	55	0.83 (0.56–1.24)	.37
≥ 1000	57	61	0.90 (0.63–1.29)	.57		25	29	0.83 (0.48–1.41)	.49
Current multivitamin use				.71					.96
Yes	43	48	0.90 (0.60–1.36)	.62		15	18	0.84 (0.42–1.67)	.62
No	144	144	0.99 (0.78–1.24)	.91		55	66	0.82 (0.58–1.18)	.28
Randomized to receive vitamin E				.65					.90
Yes	87	93	0.92 (0.69–1.23)	.58		36	42	0.84 (0.54–1.32)	.45
No	100	99	1.01 (0.77–1.34)	.93		34	42	0.81 (0.52–1.27)	.36
Randomized to receive vitamin C				.06					.36
Yes	87	108	0.81 (0.61–1.07)	.13		33	46	0.72 (0.46–1.12)	.14
No	100	84	1.18 (0.88–1.58)	.27		37	38	0.97 (0.61–1.52)	.88
Randomized to receive β-carotene			.12					.15
Yes	91	108	0.83 (0.63–1.10)	.19		33	49	0.66 (0.43–1.03)	.07
No	96	84	1.15 (0.86–1.54)	.36		37	35	1.06 (0.67–1.69)	.80
Total folate intakeg, median value			.78					.77
≤ 431.5 μg/day	94	88	1.01 (0.75–1.35)	.97		36	38	0.90 (0.57–1.41)	.63
> 431.5 μg/day	87	96	0.95 (0.71–1.27)	.74		32	41	0.82 (0.51–1.30)	.39
Total vitamin B6 intakeg, median value			.73					.63
≤ 2.5 mg/day	91	92	0.94 (0.71–1.26)	.68		33	40	0.79 (0.50–1.25)	.32
> 2.5 mg/day	90	92	1.01 (0.76–1.36)	.93		35	39	0.92 (0.59–1.46)	.74
Total vitamin B12 intakeg, median value			.10					.39
≤ 7.0 μg/day	88	106	0.83 (0.62–1.10)	.19		32	43	0.74 (0.47–1.18)	.20
> 7.0 μg/day	93	78	1.18 (0.87–1.59)	.29		36	36	0.99 (0.62–1.57)	.96

Abbreviations: CVD: cardiovascular disease

^aExcluding non-melanoma skin cancer.

^bReported history of myocardial infarction, stroke, coronary revascularization, angina pectoris, transient ischemic attack, carotid endarterectomy, or peripheral artery surgery.

^cDenotes women with no prior CVD but with at least 3 of the following: hypertension, high cholesterol level, diabetes mellitus, parental history of premature myocardial infarction (before age 60 years), obesity (body mass index ≥30 kg/m²), current cigarette smoking, and inconsistent report of prior CVD.

^dExcept for non-melanoma skin cancers.

^eBody mass index is calculated as weight in kilograms divided by height in meters squared.

^fAmong postmenopausal women only.

^gCalculated from the food frequency questionnaire.