Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies

Table 2 Subgroup analyses of studies reporting risk of colorectal adenomas for the highest vs lowest (reference) category of markers of inflammation

Subgroup	CRP				IL-6				TNF-α
	No. of datasets	RR (95%CI)	I2	Pheterogeneity	No. of datasets	RR (95%CI)	I2	Pheterogeneity	No. of datasets	RR (95%CI)	I2	Pheterogeneity
Total	12	1.23 (0.98, 1.54)	54%	0.01	7	1.19 (0.92, 1.55)	46%	0.09	6	1.00 (0.77, 1.29)	49%	0.08
Study design
Nested case-control	3	0.81 (0.54, 1.21)	49%	0.14	2	1.02 (0.72, 1.45)	0%	0.47	1	1.14 (0.55, 2.36)	NA	NA
Case-control	8	1.39 (1.11, 1.74)	34%	0.16	5	1.25 (0.89, 1.78)	59%	0.04	5	0.98 (0.73, 1.31)	59%	0.05
Cross-sectional	1	2.16 (0.81, 5.75)	NA	NA	0	NA	NA	NA	0	NA	NA	NA
Gender
Men	2	1.34 (0.79, 2.28)	25%	0.25	1	2.06 (1.02, 4.16)	NA	NA	1	0.94 (0.68, 1.30)	NA	NA
Women	1	1.10 (0.76, 1.59)	NA	NA	1	0.96 (0.65, 1.42)	NA	NA	1	0.65 (0.41, 1.03)	NA	NA
Geographical location
United States	9	1.14 (0.89, 1.47)	57%	0.02	5	1.14 (0.86, 1.52)	52%	0.08	3	1.23 (0.87, 1.72)	44%	0.17
United Kingdom	1	2.95 (1.22, 7.13)	NA	NA	1	1.00 (0.44, 2.27)	NA	NA	1	0.73 (0.32, 1.67)	NA	NA
Japan	2	1.34 (0.79, 2.28)	25%	0.25	1	2.06 (1.02, 4.16)	NA	NA	2	0.81 (0.57, 1.16)	39%	0.20
By adjustment for confounders
BMI/obesity
Yes	8	1.12 (0.86, 1.45)	54%	0.03	6	1.19 (0.89, 1.58)	55%	0.05	5	0.98 (0.73, 1.31)	59%	0.05
No	4	1.54 (1.01, 2.37)	49%	0.12	1	1.35 (0.58, 3.14)	NA	NA	1	1.14 (0.55, 2.36)	NA	NA
Smoking
Yes	6	1.01 (0.73, 1.40)	56%	0.04	5	1.03 (0.83, 1.29)	9%	0.35	4	0.90 (0.74, 1.09)	0%	0.42
No	6	1.48 (1.17, 1.88)	15%	0.32	2	1.74 (1.22, 2.49)	0%	0.52	2	1.51 (1.05, 2.16)	0%	0.39
Aspirin/NSAIDs use
Yes	4	1.00 (0.58, 1.72)	72%	0.01	3	0.99 (0.78, 1.26)	0%	0.98	4	0.90 (0.74, 1.09)	0%	0.42
No	8	1.35 (1.10, 1.65)	17%	0.30	4	1.43 (0.93, 2.21)	58%	0.07	2	1.51 (1.05, 2.16)	0%	0.39
Alcohol consumption
Yes	3	1.32 (0.87, 2.03)	53%	0.12	3	1.20 (0.75, 1.92)	44%	0.17	3	0.82 (0.64, 1.06)	0%	0.42
No	9	1.19 (0.89, 1.59)	60%	0.01	4	1.20 (0.83, 1.73)	60%	0.06	3	1.23 (0.87, 1.72)	44%	0.17
Energy/physical activity
Yes	4	1.32 (0.97, 1.79)	34%	0.21	2	0.97 (0.68, 1.38)	0%	0.93	1	0.73 (0.32, 1.67)	NA	NA
No	8	1.16 (0.84, 1.61)	63%	0.008	5	1.30 (0.92, 1.84)	58%	0.05	5	1.02 (0.78, 1.35)	56%	0.06
Family history of colorectal neoplasia
Yes	5	0.98 (0.73, 1.32)	49%	0.10	3	1.13 (0.80, 1.61)	47%	0.15	3	0.90 (0.71, 1.13)	22%	0.28
No	7	1.49 (1.11, 1.99)	43%	0.11	4	1.24 (0.81, 1.90)	53%	0.10	3	1.24 (0.78, 1.97)	38%	0.20
Sample fasting status
Yes	6	1.29 (1.01, 1.64)	25%	0.25	7	1.19 (0.92, 1.55)	46%	0.09	6	1.00 (0.77, 1.29)	49%	0.08
No	6	1.12 (0.75, 1.68)	70%	0.005	0	NA	NA	NA	0	NA	NA	NA
Measurement method
ELISA	1	1.45 (0.95, 2.21)	NA	NA	5	1.21 (0.88, 1.67)	63%	0.03	1	1.65 (1.09, 2.50)	NA	NA
INA	4	1.54 (1.06, 2.23)	29%	0.24	0	NA	NA	NA	0	NA	NA	NA
ITA	5	1.26 (0.94, 1.69)	45%	0.12	0	NA	NA	NA	0	NA	NA	NA
Cytokine/Chemokine Magnetic Bead Panel Assay	0	NA	NA	NA	1	1.35 (0.58, 3.14)	NA	NA	4	0.92 (0.76, 1.11)	0%	0.41
Cytometric Bead Assay	0	NA	NA	NA	1	1.00 (0.44, 2.27)	NA	NA	1	0.73 (0.32, 1.67)	NA	NA
Dade-Behring method	1	0.61 (0.29, 1.28)	NA	NA	0	NA	NA	NA	0	NA	NA	NA
Chemiluminescent Immunometric Assay	1	0.65 (0.41, 1.03)	NA	NA	0	NA	NA	NA	0	NA	NA	NA

BMI: Body mass index; ELISA: Enzyme-linked immunosorbent assay; NA: Not applicable; NSAIDs: Non-steroidal anti-inflammatory drugs; INA: Immunonephelometric assay; ITA: Immunoturbidimetric assay; CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha.