Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 6, Number 2, April 2013, pages 43-48

No Association between Circulating Levels and Genetic Variants of IL-6 and TNF-α and Colon Adenoma

**Table 1.** Characteristics of Study Sample by Race and Case/Control Status
Characteristic*	Caucasians	African Americans
^*Values for continuous variables are mean (SD); for categorical variables, values are for percentages. Two-sided comparisons were computed using independent samples t-tests for continuous and by χ square test for categorical variables.
Age, yr	57.1 (8.0)	54.5 (8.7)	0.001	58.1 (8.3)	54.8 (8.6)	0.001
Sex, % male	51.5	38.4	0.001	40.2	24.8	0.001
Body mass index, kg/m²	29.0 (6.2)	27.7 (5.9)	0.005	31.6 (7.9)	32.1 (7.7)	0.45
Waist circumference, cm	39.0 (6.6)	37.1 (6.3)	0.001	41.4 (7.9)	40.8 (7.0)	0.37
Waist-to-hip ratio	0.92 (0.09)	0.90 (0.09)	0.001	0.96 (0.09)	0.93 (0.09)	0.001
NSAID use	41.0	34.5	0.08	36.2	35.5	0.87
Smoking status:			0.37			0.02
Never	46.3	51.1		30.5	38.9
Former	41.4	39.0		32.8	35.5
Current	12.3	9.9		36.8	25.6
Pack years of smoking	12.2 (26.2)	14.5 (107.3)	0.75	15.1 (20.6)	9.9 (23.7)	0.01
Family history of colorectal cancer, %	28.2	25.2	0.37	16.1	23.8	0.04
IL-6, pg/mL	2.5 (2.1)	2.2 (1.8)	0.07	3.7 (2.7)	3.4 (2.3)	0.10
TNF-α, pg/mL	5.1 (11.3)	4.2 (2.5)	0.23	4.5 (2.7)	4.6 (6.0)	0.78
Insulin, µIU/mL	7.5 (11.5) (n = 182)	6.0 (7.1) (n = 556)	0.10	15.3 (61.5) (n = 129)	10.0 (14.2) (n = 261)	0.19
Fasting glucose, mg/dL	86.3 (17.3) (n = 184)	85.3 (24.6) (n = 569)	0.59	97.9 (29.1) (n = 129)	94.2 (37.5) (n = 262)	0.33

Table 1. Characteristics of Study Sample by Race and Case/Control Status

Characteristic*

Caucasians

African Americans

Cases (n = 227)

Controls (n = 667)

P-value

Cases (n = 174)

Controls (n = 383)

P-value

^*Values for continuous variables are mean (SD); for categorical variables, values are for percentages. Two-sided comparisons were computed using independent samples t-tests for continuous and by χ square test for categorical variables.

Age, yr

57.1 (8.0)

54.5 (8.7)

0.001

58.1 (8.3)

54.8 (8.6)

0.001

Sex, % male

51.5

38.4

0.001

40.2

24.8

0.001

Body mass index, kg/m²

29.0 (6.2)

27.7 (5.9)

0.005

31.6 (7.9)

32.1 (7.7)

0.45

Waist circumference, cm

39.0 (6.6)

37.1 (6.3)

0.001

41.4 (7.9)

40.8 (7.0)

0.37

Waist-to-hip ratio

0.92 (0.09)

0.90 (0.09)

0.001

0.96 (0.09)

0.93 (0.09)

0.001

NSAID use

41.0

34.5

0.08

36.2

35.5

0.87

Smoking status:

0.37

0.02

Never

46.3

51.1

30.5

38.9

Former

41.4

39.0

32.8

35.5

Current

12.3

9.9

36.8

25.6

Pack years of smoking

12.2 (26.2)

14.5 (107.3)

0.75

15.1 (20.6)

9.9 (23.7)

0.01

Family history of colorectal cancer, %

28.2

25.2

0.37

16.1

23.8

0.04

IL-6, pg/mL

2.5 (2.1)

2.2 (1.8)

0.07

3.7 (2.7)

3.4 (2.3)

0.10

TNF-α, pg/mL

5.1 (11.3)

4.2 (2.5)

0.23

4.5 (2.7)

4.6 (6.0)

0.78

Insulin, µIU/mL

7.5 (11.5) (n = 182)

6.0 (7.1) (n = 556)

0.10

15.3 (61.5) (n = 129)

10.0 (14.2) (n = 261)

0.19

Fasting glucose, mg/dL

86.3 (17.3) (n = 184)

85.3 (24.6) (n = 569)

0.59

97.9 (29.1) (n = 129)

94.2 (37.5) (n = 262)

0.33

**Table 2.** Association of Colon Adenomas and Circulating IL-6 and TNF-α
Category^*	Caucasian	African-American	All subjects
^For Caucasians, the IL-6 cutoffs were 1.25 pg/mL& 2.22 pg/mL; for African American, 2.00 pg/mL & 3.83 pg/mL; for all subjects, cutoffs were 1.44 pg/mL & 2.71 pg/mL. For Caucasian, the TNF-α cutoffs were 3.02 pg/mL & 4.50 pg/mL; for African Americans, 3.00 pg/mL & 4.42 pg/mL; for all subjects, cutoffs were 3.01 pg/mL &4.46 pg/mL.Adjusted for age, sex, non-steroidal anti-inflammatory use, BMI, family history of colorectal cancer, and smoking status. **Also adjusted for race.
IL-6
Tertile 1	73	224	1.00	1.00	62	129	1.00	1.00	113	352	1.00	1.00
Tertile 2	67	221	0.93 (0.64 - 1.36)	0.77 (0.52 - 1.16)	43	128	0.70 (0.44 - 1.11)	0.58 (0.36 - 0.95)	136	348	1.22 (0.91 - 1.63)	1.06 (0.78 - 1.44)
Tertile 3	87	222	1.20 (0.84 - 1.73)	0.87 (0.57 - 1.32)	69	126	1.14 (0.75 - 1.74)	1.00 (0.62 - 1.61)	152	350	1.35 (1.02 - 1.80)	1.01 (0.72 - 1.40)
p for trend			0.05	0.53			0.08	0.13			0.002	0.10
TNF-α
Tertile 1	71	222	1.00	1.00	51	128	1.00	1.00	123	350	1.00	1.00
Tertile 2	66	223	0.93 (0.63 - 1.36)	0.78 (0.52 - 1.16)	54	128	1.06 (0.67 - 1.67)	1.06 (0.66 - 1.71)	120	351	0.97 (0.73 - 1.30)	0.85 (0.63 - 1.15)
Tertile 3	90	222	1.27 (0.88 - 1.82)	0.94 (0.63 - 1.39)	69	127	1.36 (0.88 - 2.11)	1.14 (0.72 - 1.81)	158	349	1.29 (0.98 - 1.70)	1.01 (0.75 - 1.36)
P for trend			0.23	0.20			0.78	0.55			0.20	0.39

Table 2. Association of Colon Adenomas and Circulating IL-6 and TNF-α

Category^*

Caucasian

African-American

All subjects

Cases n = 227

Controls n = 667

Crude OR (95% CI)

Adjusted OR^** (95% CI)

Cases n = 174

Controls n = 383

Crude OR (95% CI)

Adjusted OR^** (95% CI)

Cases n = 401

Controls n = 1,050

Crude OR (95% CI)

Adjusted OR^*** (95% CI)

^*For Caucasians, the IL-6 cutoffs were 1.25 pg/mL& 2.22 pg/mL; for African American, 2.00 pg/mL & 3.83 pg/mL; for all subjects, cutoffs were 1.44 pg/mL & 2.71 pg/mL. For Caucasian, the TNF-α cutoffs were 3.02 pg/mL & 4.50 pg/mL; for African Americans, 3.00 pg/mL & 4.42 pg/mL; for all subjects, cutoffs were 3.01 pg/mL &4.46 pg/mL.**Adjusted for age, sex, non-steroidal anti-inflammatory use, BMI, family history of colorectal cancer, and smoking status. ***Also adjusted for race.

IL-6

Tertile 1

224

1.00

129

1.00

113

352

1.00

Tertile 2

221

0.93 (0.64 - 1.36)

0.77 (0.52 - 1.16)

128

0.70 (0.44 - 1.11)

0.58 (0.36 - 0.95)

136

348

1.22 (0.91 - 1.63)

1.06 (0.78 - 1.44)

Tertile 3

222

1.20 (0.84 - 1.73)

0.87 (0.57 - 1.32)

126

1.14 (0.75 - 1.74)

1.00 (0.62 - 1.61)

152

350

1.35 (1.02 - 1.80)

1.01 (0.72 - 1.40)

p for trend

0.05

0.53

0.08

0.13

0.002

0.10

TNF-α

Tertile 1

222

1.00

128

1.00

123

350

1.00

Tertile 2

223

0.93 (0.63 - 1.36)

0.78 (0.52 - 1.16)

128

1.06 (0.67 - 1.67)

1.06 (0.66 - 1.71)

120

351

0.97 (0.73 - 1.30)

0.85 (0.63 - 1.15)

Tertile 3

222

1.27 (0.88 - 1.82)

0.94 (0.63 - 1.39)

127

1.36 (0.88 - 2.11)

1.14 (0.72 - 1.81)

158

349

1.29 (0.98 - 1.70)

1.01 (0.75 - 1.36)

P for trend

0.23

0.20

0.78

0.55

0.20

0.39

**Table 3.** Association of IL-6 and TNF-α Genotypes With Colorectal Adenomas
Gene	SNP	Alleles (m/M)	MAF cases	MAF controls	Caucasians Adjusted OR* (95% CI)	African Americans Adjusted OR* (95% CI)	All Subjects Adjusted OR** (95% CI)
^Odds ratios and 95% confidence intervals adjusted for age, sex, non-steroidal inflammatory drug use, BMI, family history of colorectal cancer, and smoking status. *In addition, adjusted for race.
IL-6	rs2069840	G/C	0.23	0.27	0.89 (0.71 - 1.13)	0.75 (0.50 - 1.11)	0.86 (0.71 - 1.06)
IL-6	rs1554606	A/C	0.39	0.39	1.08 (0.87 - 1.34)	0.92 (0.69 - 1.23)	1.01 (0.85 - 1.21)
IL-6	rs2069827	T/G	0.05	0.06	0.86 (0.58 - 1.29)	0.82 (0.28 - 2.40)	0.84 (0.57 - 1.22)
IL-6	rs2069849	A/G	0.08	0.07	1.47 (0.78 - 2.76)	0.93 (0.64 - 1.35)	1.05 (0.76 - 1.45)
TNF-α	rs3093662	G/A	0.07	0.07	1.15 (0.78 - 1.70)	0.78 (0.45 - 1.34)	0.99 (0.72 - 1.36)
TNF-α	rs1799964	G/A	0.18	0.18	1.05 (0.80 - 1.38)	1.11 (0.77 - 1.61)	1.06 (0.85 - 1.32

Table 3. Association of IL-6 and TNF-α Genotypes With Colorectal Adenomas

Gene

SNP

Alleles (m/M)

MAF cases

MAF controls

Caucasians Adjusted OR* (95% CI)

African Americans Adjusted OR* (95% CI)

All Subjects Adjusted OR** (95% CI)

^*Odds ratios and 95% confidence intervals adjusted for age, sex, non-steroidal inflammatory drug use, BMI, family history of colorectal cancer, and smoking status. **In addition, adjusted for race.

IL-6

rs2069840

G/C

0.23

0.27

0.89 (0.71 - 1.13)

0.75 (0.50 - 1.11)

0.86 (0.71 - 1.06)

IL-6

rs1554606

A/C

0.39

1.08 (0.87 - 1.34)

0.92 (0.69 - 1.23)

1.01 (0.85 - 1.21)

IL-6

rs2069827

T/G

0.05

0.06

0.86 (0.58 - 1.29)

0.82 (0.28 - 2.40)

0.84 (0.57 - 1.22)

IL-6

rs2069849

A/G

0.08

0.07

1.47 (0.78 - 2.76)

0.93 (0.64 - 1.35)

1.05 (0.76 - 1.45)

TNF-α

rs3093662

G/A

0.07

1.15 (0.78 - 1.70)

0.78 (0.45 - 1.34)

0.99 (0.72 - 1.36)

TNF-α

rs1799964

G/A

0.18

1.05 (0.80 - 1.38)

1.11 (0.77 - 1.61)

1.06 (0.85 - 1.32