Table 3. Open in new tab Univariable and...

	Univariable model	Multivariable model ^b
Multivitamin supplement intake
Never ^a	573	1403	58122	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	137	465	19924	0.49 (0.37–0.64)	< 0.001	0.52 (0.36–0.75)	< 0.001	0.55 (0.40–0.75)	< 0.001
1 month to 11.9 months	25	106	3777	0.58 (0.35–0.98)	0.04	0.46 (0.25–0.85)	0.01	0.55 (0.30–0.99)	0.05
1 year to 2.9 years	40	122	5132	0.70 (0.43–1.14)	0.15	0.67 (0.37–1.22)	0.19	0.69 (0.41–1.17)	0.17
≥ 3 years	72	237	11015	0.38 (0.28–0.53)	< 0.001	0.45 (0.29–0.69)	< 0.001	0.47 (0.32–0.69)	< 0.001
Multivitamin supplement intake (per year)	710	1868	78046	0.93 (0.90 – 0.96)	< 0.001	0.93 (0.89–0.97)	0.001	0.95 (0.91–0.98)	0.003
Calcium supplement intake
Never ^a	685	1730	71025	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	48	178	8635	0.29 (0.20–0.41)	< 0.001	0.44 (0.27–0.71)	0.001	0.46 (0.30–0.71)	< 0.001
1 month to 11.9 months	4	35	1347	0.40 (0.05–0.51)	0.002	0.28 (0.07–1.12)	0.07	0.32 (0.09–1.11)	0.07
1 year to 2.9 years	19	60	2738	0.40 (0.23–0.68)	0.001	0.60 (0.30–1.20)	0.15	0.60 (0.32–1.13)	0.11
≥ 3 years	25	83	4550	0.27 (0.17–0.43)	< 0.001	0.40 (0.21–0.76)	0.01	0.42 (0.23–0.74)	0.003
Calcium supplement intake (per year)	733	1908	79660	0.84 (0.76 – 0.93)	0.001	0.87 (0.79–0.99)	0.002	0.90 (0.83–0.98)	0.02
Acid folic supplement intake
Never ^a	693	1766	74195	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥1 month	37	154	6225	0.51 (0.32–0.79)	0.003	1.05 (0.64–1.75)	0.84	0.95 (0.58–1.53)	0.82
1 month to 11.9 months	11	68	2627	0.31 (0.14–0.70)	0.004	0.64 (0.25–1.59)	0.33	0.60 (0.25–1.41)	0.24
1 year to 2.9 years	18	56	2258	0.84 (0.44–1.60)	0.60	1.50 (0.76–2.97)	0.24	1/39 (0.72–2.69)	0.33
≥ 3 years	8	30	1340	0.40 (0.18–0.89)	0.02	1.24 (0.52–2.98)	0.63	0.87 (0.36–2.08)	0.76
Acid folic supplement intake (per year)	730	1920	80420	0.86 (0.74–1.00)	0.05	0.97 (0.92–1.02)	0.22	0.96 (0.90–1.01)	0.14
Any supplement intake
None of three ^a	541	1252	51604	1 (ref)	–	1 (ref)	–	1 (ref)	–
Multivitamin only	86	281	11694	0.50 (0.36–0.70)	< 0.001	0.46 (0.29–0.72)	< 0.001	0.51 (0.35–0.74)	< 0.001
Calcium only	6	40	1949	0.11 (0.05–0.26)	< 0.001	0.23 (0.08–0.69)	0.01	0.22 (0.08–0.60)	0.003
Folic acid only	10	52	2007	0.31 (0.13–0.75)	0.009	0.70 (0.27–1.84)	0.47	0.63 (0.25–1.56)	0.32
Multivitamin and calcium	26	87	4305	0.27 (0.17–0.44)	< 0.001	0.28 (0.14–0.57)	< 0.001	0.36 (0.20–0.64)	< 0.001
Multivitamin and folic acid	12	49	1841	0.59 (0.27–1.28)	0.18	0.93 (0.38–2.24)	0.87	0.92 (0.41–2.03)	0.83
Calcium and folic acid	4	16	750	0.23 (0.07–0.76)	0.02	0.40 (0.12–1.42)	0.16	0.39 (0.11–1.37)	0.14
All of three	10	29	1294	0.53 (0.25–1.10)	0.09	1.54 (0.79–3.00)	0.21	1.08 (0.48–2.46)	0.84

Univariable model

Multivariable model ^b

Complete case analysis

Multiple imputation

No. of carriers with colorectal cancer

Total no. of carriers

Person-years

HR (95% CI)

P -value

HR (95% CI)

P -value

HR (95% CI)

P -value

Multivitamin supplement intake

Never ^a

573

1403

58122

1 (ref)

–

1 (ref)

–

1 (ref)

–

≥ 1 month

137

465

19924

0.49 (0.37–0.64)

< 0.001

0.52 (0.36–0.75)

< 0.001

0.55 (0.40–0.75)

< 0.001

1 month to 11.9 months

106

3777

0.58 (0.35–0.98)

0.04

0.46 (0.25–0.85)

0.01

0.55 (0.30–0.99)

0.05

1 year to 2.9 years

122

5132

0.70 (0.43–1.14)

0.15

0.67 (0.37–1.22)

0.19

0.69 (0.41–1.17)

0.17

≥ 3 years

237

11015

0.38 (0.28–0.53)

< 0.001

0.45 (0.29–0.69)

< 0.001

0.47 (0.32–0.69)

< 0.001

Multivitamin supplement intake (per year)

710

1868

78046

0.93 (0.90 – 0.96)

< 0.001

0.93 (0.89–0.97)

0.001

0.95 (0.91–0.98)

0.003

Calcium supplement intake

Never ^a

685

1730

71025

1 (ref)

–

1 (ref)

–

1 (ref)

–

≥ 1 month

178

8635

0.29 (0.20–0.41)

< 0.001

0.44 (0.27–0.71)

0.001

0.46 (0.30–0.71)

< 0.001

1 month to 11.9 months

1347

0.40 (0.05–0.51)

0.002

0.28 (0.07–1.12)

0.07

0.32 (0.09–1.11)

0.07

1 year to 2.9 years

2738

0.40 (0.23–0.68)

0.001

0.60 (0.30–1.20)

0.15

0.60 (0.32–1.13)

0.11

≥ 3 years

4550

0.27 (0.17–0.43)

< 0.001

0.40 (0.21–0.76)

0.01

0.42 (0.23–0.74)

0.003

Calcium supplement intake (per year)

733

1908

79660

0.84 (0.76 – 0.93)

0.001

0.87 (0.79–0.99)

0.002

0.90 (0.83–0.98)

0.02

Acid folic supplement intake

Never ^a

693

1766

74195

1 (ref)

–

1 (ref)

–

1 (ref)

–

≥1 month

154

6225

0.51 (0.32–0.79)

0.003

1.05 (0.64–1.75)

0.84

0.95 (0.58–1.53)

0.82

1 month to 11.9 months

2627

0.31 (0.14–0.70)

0.004

0.64 (0.25–1.59)

0.33

0.60 (0.25–1.41)

0.24

1 year to 2.9 years

2258

0.84 (0.44–1.60)

0.60

1.50 (0.76–2.97)

0.24

1/39 (0.72–2.69)

0.33

≥ 3 years

1340

0.40 (0.18–0.89)

0.02

1.24 (0.52–2.98)

0.63

0.87 (0.36–2.08)

0.76

Acid folic supplement intake (per year)

730

1920

80420

0.86 (0.74–1.00)

0.05

0.97 (0.92–1.02)

0.22

0.96 (0.90–1.01)

0.14

Any supplement intake

None of three ^a

541

1252

51604

1 (ref)

–

1 (ref)

–

1 (ref)

–

Multivitamin only

281

11694

0.50 (0.36–0.70)

< 0.001

0.46 (0.29–0.72)

< 0.001

0.51 (0.35–0.74)

< 0.001

Calcium only

1949

0.11 (0.05–0.26)

< 0.001

0.23 (0.08–0.69)

0.01

0.22 (0.08–0.60)

0.003

Folic acid only

2007

0.31 (0.13–0.75)

0.009

0.70 (0.27–1.84)

0.47

0.63 (0.25–1.56)

0.32

Multivitamin and calcium

4305

0.27 (0.17–0.44)

< 0.001

0.28 (0.14–0.57)

< 0.001

0.36 (0.20–0.64)

< 0.001

Multivitamin and folic acid

1841

0.59 (0.27–1.28)

0.18

0.93 (0.38–2.24)

0.87

0.92 (0.41–2.03)

0.83

Calcium and folic acid

750

0.23 (0.07–0.76)

0.02

0.40 (0.12–1.42)

0.16

0.39 (0.11–1.37)

0.14

All of three

1294

0.53 (0.25–1.10)

0.09

1.54 (0.79–3.00)

0.21

1.08 (0.48–2.46)

0.84

	Univariable model	Multivariable model ^b
Multivitamin supplement intake
Never ^a	573	1403	58122	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	137	465	19924	0.49 (0.37–0.64)	< 0.001	0.52 (0.36–0.75)	< 0.001	0.55 (0.40–0.75)	< 0.001
1 month to 11.9 months	25	106	3777	0.58 (0.35–0.98)	0.04	0.46 (0.25–0.85)	0.01	0.55 (0.30–0.99)	0.05
1 year to 2.9 years	40	122	5132	0.70 (0.43–1.14)	0.15	0.67 (0.37–1.22)	0.19	0.69 (0.41–1.17)	0.17
≥ 3 years	72	237	11015	0.38 (0.28–0.53)	< 0.001	0.45 (0.29–0.69)	< 0.001	0.47 (0.32–0.69)	< 0.001
Multivitamin supplement intake (per year)	710	1868	78046	0.93 (0.90 – 0.96)	< 0.001	0.93 (0.89–0.97)	0.001	0.95 (0.91–0.98)	0.003
Calcium supplement intake
Never ^a	685	1730	71025	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	48	178	8635	0.29 (0.20–0.41)	< 0.001	0.44 (0.27–0.71)	0.001	0.46 (0.30–0.71)	< 0.001
1 month to 11.9 months	4	35	1347	0.40 (0.05–0.51)	0.002	0.28 (0.07–1.12)	0.07	0.32 (0.09–1.11)	0.07
1 year to 2.9 years	19	60	2738	0.40 (0.23–0.68)	0.001	0.60 (0.30–1.20)	0.15	0.60 (0.32–1.13)	0.11
≥ 3 years	25	83	4550	0.27 (0.17–0.43)	< 0.001	0.40 (0.21–0.76)	0.01	0.42 (0.23–0.74)	0.003
Calcium supplement intake (per year)	733	1908	79660	0.84 (0.76 – 0.93)	0.001	0.87 (0.79–0.99)	0.002	0.90 (0.83–0.98)	0.02
Acid folic supplement intake
Never ^a	693	1766	74195	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥1 month	37	154	6225	0.51 (0.32–0.79)	0.003	1.05 (0.64–1.75)	0.84	0.95 (0.58–1.53)	0.82
1 month to 11.9 months	11	68	2627	0.31 (0.14–0.70)	0.004	0.64 (0.25–1.59)	0.33	0.60 (0.25–1.41)	0.24
1 year to 2.9 years	18	56	2258	0.84 (0.44–1.60)	0.60	1.50 (0.76–2.97)	0.24	1/39 (0.72–2.69)	0.33
≥ 3 years	8	30	1340	0.40 (0.18–0.89)	0.02	1.24 (0.52–2.98)	0.63	0.87 (0.36–2.08)	0.76
Acid folic supplement intake (per year)	730	1920	80420	0.86 (0.74–1.00)	0.05	0.97 (0.92–1.02)	0.22	0.96 (0.90–1.01)	0.14
Any supplement intake
None of three ^a	541	1252	51604	1 (ref)	–	1 (ref)	–	1 (ref)	–
Multivitamin only	86	281	11694	0.50 (0.36–0.70)	< 0.001	0.46 (0.29–0.72)	< 0.001	0.51 (0.35–0.74)	< 0.001
Calcium only	6	40	1949	0.11 (0.05–0.26)	< 0.001	0.23 (0.08–0.69)	0.01	0.22 (0.08–0.60)	0.003
Folic acid only	10	52	2007	0.31 (0.13–0.75)	0.009	0.70 (0.27–1.84)	0.47	0.63 (0.25–1.56)	0.32
Multivitamin and calcium	26	87	4305	0.27 (0.17–0.44)	< 0.001	0.28 (0.14–0.57)	< 0.001	0.36 (0.20–0.64)	< 0.001
Multivitamin and folic acid	12	49	1841	0.59 (0.27–1.28)	0.18	0.93 (0.38–2.24)	0.87	0.92 (0.41–2.03)	0.83
Calcium and folic acid	4	16	750	0.23 (0.07–0.76)	0.02	0.40 (0.12–1.42)	0.16	0.39 (0.11–1.37)	0.14
All of three	10	29	1294	0.53 (0.25–1.10)	0.09	1.54 (0.79–3.00)	0.21	1.08 (0.48–2.46)	0.84

Univariable model

Multivariable model ^b

Complete case analysis

Multiple imputation

No. of carriers with colorectal cancer

Total no. of carriers

Person-years

HR (95% CI)

P -value

HR (95% CI)

P -value

HR (95% CI)

P -value

Multivitamin supplement intake

Never ^a

573

1403

58122

1 (ref)

–

1 (ref)

–

1 (ref)

–

≥ 1 month

137

465

19924

0.49 (0.37–0.64)

< 0.001

0.52 (0.36–0.75)

< 0.001

0.55 (0.40–0.75)

< 0.001

1 month to 11.9 months

106

3777

0.58 (0.35–0.98)

0.04

0.46 (0.25–0.85)

0.01

0.55 (0.30–0.99)

0.05

1 year to 2.9 years

122

5132

0.70 (0.43–1.14)

0.15

0.67 (0.37–1.22)

0.19

0.69 (0.41–1.17)

0.17

≥ 3 years

237

11015

0.38 (0.28–0.53)

< 0.001

0.45 (0.29–0.69)

< 0.001

0.47 (0.32–0.69)

< 0.001

Multivitamin supplement intake (per year)

710

1868

78046

0.93 (0.90 – 0.96)

< 0.001

0.93 (0.89–0.97)

0.001

0.95 (0.91–0.98)

0.003

Calcium supplement intake

Never ^a

685

1730

71025

1 (ref)

–

1 (ref)

–

1 (ref)

–

≥ 1 month

178

8635

0.29 (0.20–0.41)

< 0.001

0.44 (0.27–0.71)

0.001

0.46 (0.30–0.71)

< 0.001

1 month to 11.9 months

1347

0.40 (0.05–0.51)

0.002

0.28 (0.07–1.12)

0.07

0.32 (0.09–1.11)

0.07

1 year to 2.9 years

2738

0.40 (0.23–0.68)

0.001

0.60 (0.30–1.20)

0.15

0.60 (0.32–1.13)

0.11

≥ 3 years

4550

0.27 (0.17–0.43)

< 0.001

0.40 (0.21–0.76)

0.01

0.42 (0.23–0.74)

0.003

Calcium supplement intake (per year)

733

1908

79660

0.84 (0.76 – 0.93)

0.001

0.87 (0.79–0.99)

0.002

0.90 (0.83–0.98)

0.02

Acid folic supplement intake

Never ^a

693

1766

74195

1 (ref)

–

1 (ref)

–

1 (ref)

–

≥1 month

154

6225

0.51 (0.32–0.79)

0.003

1.05 (0.64–1.75)

0.84

0.95 (0.58–1.53)

0.82

1 month to 11.9 months

2627

0.31 (0.14–0.70)

0.004

0.64 (0.25–1.59)

0.33

0.60 (0.25–1.41)

0.24

1 year to 2.9 years

2258

0.84 (0.44–1.60)

0.60

1.50 (0.76–2.97)

0.24

1/39 (0.72–2.69)

0.33

≥ 3 years

1340

0.40 (0.18–0.89)

0.02

1.24 (0.52–2.98)

0.63

0.87 (0.36–2.08)

0.76

Acid folic supplement intake (per year)

730

1920

80420

0.86 (0.74–1.00)

0.05

0.97 (0.92–1.02)

0.22

0.96 (0.90–1.01)

0.14

Any supplement intake

None of three ^a

541

1252

51604

1 (ref)

–

1 (ref)

–

1 (ref)

–

Multivitamin only

281

11694

0.50 (0.36–0.70)

< 0.001

0.46 (0.29–0.72)

< 0.001

0.51 (0.35–0.74)

< 0.001

Calcium only

1949

0.11 (0.05–0.26)

< 0.001

0.23 (0.08–0.69)

0.01

0.22 (0.08–0.60)

0.003

Folic acid only

2007

0.31 (0.13–0.75)

0.009

0.70 (0.27–1.84)

0.47

0.63 (0.25–1.56)

0.32

Multivitamin and calcium

4305

0.27 (0.17–0.44)

< 0.001

0.28 (0.14–0.57)

< 0.001

0.36 (0.20–0.64)

< 0.001

Multivitamin and folic acid

1841

0.59 (0.27–1.28)

0.18

0.93 (0.38–2.24)

0.87

0.92 (0.41–2.03)

0.83

Calcium and folic acid

750

0.23 (0.07–0.76)

0.02

0.40 (0.12–1.42)

0.16

0.39 (0.11–1.37)

0.14

All of three

1294

0.53 (0.25–1.10)

0.09

1.54 (0.79–3.00)

0.21

1.08 (0.48–2.46)

0.84

Table 3.

Open in new tab

Univariable and multivariable hazard ratios for associations between intake of multivitamin, calcium and folic acid supplements and the risk of colorectal cancer for carriers of germline mutations in DNA mismatch repair genes

	Univariable model					Multivariable model ^b
						Complete case analysis		Multiple imputation
	No. of carriers with colorectal cancer	Total no. of carriers	Person-years	HR (95% CI)	P -value	HR (95% CI)	P -value	HR (95% CI)	P -value
Multivitamin supplement intake
Never ^a	573	1403	58122	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	137	465	19924	0.49 (0.37–0.64)	< 0.001	0.52 (0.36–0.75)	< 0.001	0.55 (0.40–0.75)	< 0.001
1 month to 11.9 months	25	106	3777	0.58 (0.35–0.98)	0.04	0.46 (0.25–0.85)	0.01	0.55 (0.30–0.99)	0.05
1 year to 2.9 years	40	122	5132	0.70 (0.43–1.14)	0.15	0.67 (0.37–1.22)	0.19	0.69 (0.41–1.17)	0.17
≥ 3 years	72	237	11015	0.38 (0.28–0.53)	< 0.001	0.45 (0.29–0.69)	< 0.001	0.47 (0.32–0.69)	< 0.001
Multivitamin supplement intake (per year)	710	1868	78046	0.93 (0.90 – 0.96)	< 0.001	0.93 (0.89–0.97)	0.001	0.95 (0.91–0.98)	0.003
Calcium supplement intake
Never ^a	685	1730	71025	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	48	178	8635	0.29 (0.20–0.41)	< 0.001	0.44 (0.27–0.71)	0.001	0.46 (0.30–0.71)	< 0.001
1 month to 11.9 months	4	35	1347	0.40 (0.05–0.51)	0.002	0.28 (0.07–1.12)	0.07	0.32 (0.09–1.11)	0.07
1 year to 2.9 years	19	60	2738	0.40 (0.23–0.68)	0.001	0.60 (0.30–1.20)	0.15	0.60 (0.32–1.13)	0.11
≥ 3 years	25	83	4550	0.27 (0.17–0.43)	< 0.001	0.40 (0.21–0.76)	0.01	0.42 (0.23–0.74)	0.003
Calcium supplement intake (per year)	733	1908	79660	0.84 (0.76 – 0.93)	0.001	0.87 (0.79–0.99)	0.002	0.90 (0.83–0.98)	0.02
Acid folic supplement intake
Never ^a	693	1766	74195	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥1 month	37	154	6225	0.51 (0.32–0.79)	0.003	1.05 (0.64–1.75)	0.84	0.95 (0.58–1.53)	0.82
1 month to 11.9 months	11	68	2627	0.31 (0.14–0.70)	0.004	0.64 (0.25–1.59)	0.33	0.60 (0.25–1.41)	0.24
1 year to 2.9 years	18	56	2258	0.84 (0.44–1.60)	0.60	1.50 (0.76–2.97)	0.24	1/39 (0.72–2.69)	0.33
≥ 3 years	8	30	1340	0.40 (0.18–0.89)	0.02	1.24 (0.52–2.98)	0.63	0.87 (0.36–2.08)	0.76
Acid folic supplement intake (per year)	730	1920	80420	0.86 (0.74–1.00)	0.05	0.97 (0.92–1.02)	0.22	0.96 (0.90–1.01)	0.14
Any supplement intake
None of three ^a	541	1252	51604	1 (ref)	–	1 (ref)	–	1 (ref)	–
Multivitamin only	86	281	11694	0.50 (0.36–0.70)	< 0.001	0.46 (0.29–0.72)	< 0.001	0.51 (0.35–0.74)	< 0.001
Calcium only	6	40	1949	0.11 (0.05–0.26)	< 0.001	0.23 (0.08–0.69)	0.01	0.22 (0.08–0.60)	0.003
Folic acid only	10	52	2007	0.31 (0.13–0.75)	0.009	0.70 (0.27–1.84)	0.47	0.63 (0.25–1.56)	0.32
Multivitamin and calcium	26	87	4305	0.27 (0.17–0.44)	< 0.001	0.28 (0.14–0.57)	< 0.001	0.36 (0.20–0.64)	< 0.001
Multivitamin and folic acid	12	49	1841	0.59 (0.27–1.28)	0.18	0.93 (0.38–2.24)	0.87	0.92 (0.41–2.03)	0.83
Calcium and folic acid	4	16	750	0.23 (0.07–0.76)	0.02	0.40 (0.12–1.42)	0.16	0.39 (0.11–1.37)	0.14
All of three	10	29	1294	0.53 (0.25–1.10)	0.09	1.54 (0.79–3.00)	0.21	1.08 (0.48–2.46)	0.84

	Univariable model					Multivariable model ^b
						Complete case analysis		Multiple imputation
	No. of carriers with colorectal cancer	Total no. of carriers	Person-years	HR (95% CI)	P -value	HR (95% CI)	P -value	HR (95% CI)	P -value
Multivitamin supplement intake
Never ^a	573	1403	58122	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	137	465	19924	0.49 (0.37–0.64)	< 0.001	0.52 (0.36–0.75)	< 0.001	0.55 (0.40–0.75)	< 0.001
1 month to 11.9 months	25	106	3777	0.58 (0.35–0.98)	0.04	0.46 (0.25–0.85)	0.01	0.55 (0.30–0.99)	0.05
1 year to 2.9 years	40	122	5132	0.70 (0.43–1.14)	0.15	0.67 (0.37–1.22)	0.19	0.69 (0.41–1.17)	0.17
≥ 3 years	72	237	11015	0.38 (0.28–0.53)	< 0.001	0.45 (0.29–0.69)	< 0.001	0.47 (0.32–0.69)	< 0.001
Multivitamin supplement intake (per year)	710	1868	78046	0.93 (0.90 – 0.96)	< 0.001	0.93 (0.89–0.97)	0.001	0.95 (0.91–0.98)	0.003
Calcium supplement intake
Never ^a	685	1730	71025	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥ 1 month	48	178	8635	0.29 (0.20–0.41)	< 0.001	0.44 (0.27–0.71)	0.001	0.46 (0.30–0.71)	< 0.001
1 month to 11.9 months	4	35	1347	0.40 (0.05–0.51)	0.002	0.28 (0.07–1.12)	0.07	0.32 (0.09–1.11)	0.07
1 year to 2.9 years	19	60	2738	0.40 (0.23–0.68)	0.001	0.60 (0.30–1.20)	0.15	0.60 (0.32–1.13)	0.11
≥ 3 years	25	83	4550	0.27 (0.17–0.43)	< 0.001	0.40 (0.21–0.76)	0.01	0.42 (0.23–0.74)	0.003
Calcium supplement intake (per year)	733	1908	79660	0.84 (0.76 – 0.93)	0.001	0.87 (0.79–0.99)	0.002	0.90 (0.83–0.98)	0.02
Acid folic supplement intake
Never ^a	693	1766	74195	1 (ref)	–	1 (ref)	–	1 (ref)	–
≥1 month	37	154	6225	0.51 (0.32–0.79)	0.003	1.05 (0.64–1.75)	0.84	0.95 (0.58–1.53)	0.82
1 month to 11.9 months	11	68	2627	0.31 (0.14–0.70)	0.004	0.64 (0.25–1.59)	0.33	0.60 (0.25–1.41)	0.24
1 year to 2.9 years	18	56	2258	0.84 (0.44–1.60)	0.60	1.50 (0.76–2.97)	0.24	1/39 (0.72–2.69)	0.33
≥ 3 years	8	30	1340	0.40 (0.18–0.89)	0.02	1.24 (0.52–2.98)	0.63	0.87 (0.36–2.08)	0.76
Acid folic supplement intake (per year)	730	1920	80420	0.86 (0.74–1.00)	0.05	0.97 (0.92–1.02)	0.22	0.96 (0.90–1.01)	0.14
Any supplement intake
None of three ^a	541	1252	51604	1 (ref)	–	1 (ref)	–	1 (ref)	–
Multivitamin only	86	281	11694	0.50 (0.36–0.70)	< 0.001	0.46 (0.29–0.72)	< 0.001	0.51 (0.35–0.74)	< 0.001
Calcium only	6	40	1949	0.11 (0.05–0.26)	< 0.001	0.23 (0.08–0.69)	0.01	0.22 (0.08–0.60)	0.003
Folic acid only	10	52	2007	0.31 (0.13–0.75)	0.009	0.70 (0.27–1.84)	0.47	0.63 (0.25–1.56)	0.32
Multivitamin and calcium	26	87	4305	0.27 (0.17–0.44)	< 0.001	0.28 (0.14–0.57)	< 0.001	0.36 (0.20–0.64)	< 0.001
Multivitamin and folic acid	12	49	1841	0.59 (0.27–1.28)	0.18	0.93 (0.38–2.24)	0.87	0.92 (0.41–2.03)	0.83
Calcium and folic acid	4	16	750	0.23 (0.07–0.76)	0.02	0.40 (0.12–1.42)	0.16	0.39 (0.11–1.37)	0.14
All of three	10	29	1294	0.53 (0.25–1.10)	0.09	1.54 (0.79–3.00)	0.21	1.08 (0.48–2.46)	0.84

HR, hazard ratio; CI, confidence interval.

^a Never user defined as carriers who answered ‘No’ to ‘Have you ever taken [supplement] at least twice a week for at least 1 month?’

^b Adjusted for ascertainment (binary), education (categorical), country (categorical), sex, number of screening colonoscopies (categorical), regular physical activity (binary), cigarette smoking (categorical) and intake of aspirin and/or ibuprofen (binary).

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