Oxidative Balance Score, Colorectal Adenoma, and Markers of Oxidative Stress and Inflammation

So Yeon J. Kong; Roberd M. Bostick; W. Dana Flanders; William M. McClellan; Bharat Thyagarajan; Myron D. Gross; Suzanne Judd; Michael Goodman

doi:10.1158/1055-9965.EPI-13-0619

DOI: 10.1158/1055-9965.EPI-13-0619 Published March 2014

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Table 1.

OBS assignment scheme

OBS components	Assignment scheme^a
1. PUFA intake	0 = High (3rd tertile), 1 = Medium (2nd tertile), 2 = Low (1st tertile)
2. Serum ferritin	0 = High (3rd tertile), 1 = Medium (2nd tertile), 2 = Low (1st tertile)
3. Total^b vitamin C intake	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
4. Plasma lycopene	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
5. Plasma α-carotene	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
6. Plasma β-carotene	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
7. Plasma lutein	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
8. Plasma β-cryptoxanthin	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
9. Plasma α-tocopherol	0 = Low (1st tertile), 1 = Medium (2nd tertile), 2 = High (3rd tertile)
10. Selenium supplements	0 = No supplement, 1 = Unknown (missing data), 2 = Supplement
11. Smoking history	0 = Current smoker, 1 = Former smoker, 2 = Never smoker
12. Regular aspirin use	0 = No regular use, 1 = Unknown, 2 = Regular use
13. Regular NSAID use	0 = No regular use, 1 = Unknown, 2 = Regular use
14. Alcohol consumption	0 = Above median, 1 = Below median, 2 = Nondrinker

Abbreviation: PUFA, polyunsaturated fatty acid.

↵^aLow, intermediate, and high categories correspond to study-specific tertile values among controls.
↵^bTotal intake = dietary intake + supplemental intake.

Table 2.

Selected baseline characteristics of participants in the MAP I and II case–control studies of incident, sporadic colorectal adenomas

	MAP I		MAP II		Pooled analysis
Characteristics	Cases (n = 106) mean (SD) or %	Controls (n = 109) mean (SD) or %	Cases (n = 33) mean (SD) or %	Controls (n = 92) mean (SD) or %	Cases (n = 139) mean (SD) or N (%)	Controls (n = 201) mean (SD)
Age, y	57.4 (8.9)	56.1 (10.2)	55.4 (7.3)	55.5 (7.9)	56.9 (8.6)	55.9 (9.2)
Male (%)	54.7	32.1^a	57.6	44.6	55.4	37.8^b
BMI, kg/m²	27.8 (6.1)	27.1 (5.7)	28.5 (5.2)	28.6 (6.7)	27.9 (5.9)	27.8 (6.2)
Physical activity, MET-hours/week	216.8 (143.4)	196.1 (127.3)	163.7 (116.9)	176.5 (125.2)	204.2 (139.1)	187.1 (126.4)
Family history of colorectal cancer^c (%)	17.0	33.0^a	21.1	19.6	18.0	26.9
HRT user (women only; %)	62.5	54.1	78.6	70.6	66.1	60.8
Regularly take an NSAID (%)	21.2	32.1	33.3	34.8	24.1	33.3
Regularly take aspirin (%)	34.9	35.8	45.5	41.3	37.4	38.3
Current smoker (%)	34.0	20.2^a	24.2	13.0	31.7	16.9^a
Alcohol, drinks/week	20.8 (25.6)	14.6 (20.2)	9.4 (9.1)	13.4 (16.3)	16.3 (21.4)	13.9 (17.8)
Dietary intakes per day
Total energy, kcal	2,061.3 (851.8)	2,172.6 (2493.7)	1,831.3 (765.3)	1,648.0 (647.8)	2,006.7 (835.1)	1,932.5 (1,902.0)
Total PUFA, gm	14.0 (6.3)	14.4 (14.5)	15.5 (8.9)	14.1 (10.4)	14.3 (7.0)	14.2 (12.8)
Dietary fiber, gm	22.8 (9.4)	25.5 (26.6)	16.6 (6.7)	15.3 (6.7)	21.3 (9.2)	20.9 (20.7)
Total^d vitamin C, mg	286.6 (388.5)	302.1 (354.6)	237.5 (273.6)	298.9 (369.4)	275.0 (364.2)	300.7 (360.6)
Plasma levels
Plasma lycopene, μg/dL	26.3 (14.3)	25.8 (13.3)	21.7 (11.4)	24.6 (10.8)	25.2 (13.8)	25.2 (12.2)
Plasma α-carotene, μg/dL	2.7 (2.9)	3.6 (4.8)	2.6 (2.6)	3.5 (3.1)	2.7 (2.8)	3.5 (4.1)^b
Plasma β-carotene, μg/dL	15.3 (22.5)	16.4 (15.5)	12.6 (11.4)	16.3 (13.0)	14.6 (20.4)	16.4 (14.4)
Plasma lutein, μg/dL	16.8 (7.2)	18.1 (10.3)	17.7 (6.2)	15.7 (6.3)	17.0 (6.9)	17.0 (8.7)
Plasma β-cryptoxanthin, μg/dL	6.0 (4.7)	6.9 (5.8)	6.1 (4.1)	8.1 (7.2)	6.0 (4.5)	7.5 (6.5)^b
Plasma α-tocopherol, mg/dL	1.2 (0.5)	1.1 (0.5)	1.1 (0.3)	1.2 (0.6)	1.1 (0.5)	1.2 (0.5)
Plasma γ-tocopherol, mg/dL	0.2 (0.1)	0.2 (0.1)	0.2 (0.1)	0.2 (0.1)	0.2 (0.1)	0.2 (0.1)
Plasma ferritin, mg/dL	146.1 (135.2)	148.8 (185.9)	144.5 (108.3)	130.8 (127.5)	145.7 (129.0)	140.6 (161.7)
Plasma total cholesterol, mg/dL	203.4 (35.8)	206.3 (39.5)	194.8 (32.4)	199.3 (39.5)	201.4 (35.1)	203.1 (39.6)
Biomarker levels
FIP, pg/mL	94.0 (41.8)	88.8 (38.4)	76.0 (25.0)	78.0 (28.9)	90.1 (39.3)	84.4 (35.1)
FOP, avg. std. ref. adj.^e	0.06 (0.03)	0.05 (0.02)	0.03 (0.01)	0.04 (0.01)	0.05 (0.11)	0.05 (0.13)
CRP, μg/mL	6.1 (6.1)	7.5 (23.8)	3.7 (5.0)	4.6 (6.2)	5.5 (6.0)	6.2 (18.0)

Abbreviation: PUFA, polyunsaturated fatty acid.

↵^aP < 0.01 based on t test for continuous variable and χ² test for categorical variables.
↵^bP < 0.05 based on t test for continuous variables and χ² test for categorical variables.
↵^cIn a first-degree relative.
↵^dTotal = dietary + supplemental.
↵^eUnit for FOP measurement is “average standard reference adjusted,” in which samples were calculated against a 1-ppm fluorescent reference standard quinine in 0.1 N sulfuric acid.

Table 3.

Association between OBS (with and without inclusion of γ-tocopherol) and incident, sporadic colorectal adenoma

	Cases (n)^a	Controls (n)^a	OR (95% CI)^b	P trend
OBS without γ-tocopherol (range, 2–24)
Interval 1 (OBS, 2–9)	44	43	1.0	0.04
Interval 2 (OBS, 10–16)	81	114	0.81 (0.46–1.43)
Interval 3 (OBS, 17–24)	14	44	0.39 (0.17–0.89)
OBS as continuous variable	139	201	0.93 (0.87–0.99)
OBS with γ-tocopherol (range, 2–25)
Interval 1 (OBS, 2–9)	34	31	1.0	0.04
Interval 2 (OBS, 10–17)	88	126	0.76 (0.40–1.43)
Interval 3 (OBS, 18–25)	17	44	0.40 (0.17–0.97)
OBS as continuous variable	139	201	0.93 (0.88–0.99)

↵^aTotal number of subjects in the models is lower due to missing covariate data.
↵^bAdjusted for age, race, sex, BMI, total energy intake, plasma cholesterol, and family history of colorectal cancer in a first-degree relative, hormone replacement therapy (among women), dietary fiber, physical activity, and study (MAP I or MAP II).

Table 4.

Associations between OBS and markers of oxidative stress and inflammation

	Biomarkers^a
OBS	High^c	Low^c	OR (95% CI)^b	P trend
FIP
Interval 1 (OBS, 2–9)	51	20	1.0	<0.01
Interval 2 (OBS, 10–16)	91	68	0.50 (0.25–1.01)
Interval 3 (OBS, 17–24)	17	27	0.25 (0.10–0.65)
Continuous	159	115	0.87 (0.81–0.94)
FOP
Interval 1 (OBS, 2–9)	33	45	1.0	<0.01
Interval 2 (OBS, 10–16)	107	77	2.01 (1.13–3.75)
Interval 3 (OBS, 17–24)	36	19	3.48 (1.51–8.02)
Continuous	176	141	1.10 (1.03–1.17)
CRP
Interval 1 (OBS, 2–9)	56	31	1.0	<0.01
Interval 2 (OBS, 10–16)	108	87	0.57 (0.31–1.04)
Interval 3 (OBS, 17–24)	19	39	0.21 (0.09–0.49)
Continuous	183	157	0.88 (0.82–0.94)

↵^aEach biomarker was dichotomized into “high” and “low” based on study- and sex-specific median values among controls.
↵^bAdjusted for age, race, sex, BMI, total energy intake, plasma cholesterol, and family history of colorectal cancer in a first-degree relative, hormone replacement therapy (among women), dietary fiber, physical activity, and study (MAP I or MAP II).
↵^cTotal numbers of subjects in the models differ due to missing covariate or biomarker data.

Table 5.

Associations of markers of oxidative stress and inflammation with incident, sporadic colorectal adenoma

Biomarker^a	Cases^c	Controls^c	OR (95% CI)^b	P
FIP
Low	39	76	1.0	0.03
High	80	79	1.89 (1.08–3.30)
Log (continuous)	119	155	1.38 (0.79–2.38)
FOP
Low	44	97	1.0	0.02
High	82	94	1.82 (1.11–2.99)
Log (continuous)	126	191	1.32 (0.94–1.87)
CRP
Low	55	102	1.0	0.14
High	84	99	1.45 (0.88–2.40)
Log (continuous)	139	201	1.14 (0.97–1.33)

↵^aEach biomarker was dichotomized into “high” and “low” based on sex-specific median values among controls.
↵^bAdjusted for age, race, sex, BMI, total energy intake, plasma cholesterol, and family history of colorectal cancer in a first-degree relative, hormone replacement therapy (among women), dietary fiber, physical activity, and study (MAP I or MAP II).
↵^cTotal numbers of subjects in the models differ due to missing covariate or biomarker data.

Additional Files

Tables

Supplementary Data

Files in this Data Supplement:

Supplementary Tables 1 through 4 and Supplementary Figure 1 - PDF - 145K, Supplemental Table 1: Sensitivity analyses to evaluate the impact of individual OBS components on the association between OBS and incident, sporadic colorectal adenoma. Supplemental Table 2: Associations of the OBS (in quartiles) with incident, sporadic colorectal adenoma. Supplemental Table 3: Associations of the biomarkers (divided into quartiles) with incident, sporadic colorectal adenoma. Supplemental Table 4. Association of individual OBS components with each biomarker. Supplemental Figure 1: A hypothetical directed acyclic graph (DAG) showing possible inter-relation of OBS, biomarkers of oxidative stress (FIP and FOP) and inflammation (CRP), and colorectal adenoma.