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

Table 1 Characteristics of the studies included in the meta-analysis

Ref.	Study design	Study population	No. of controls; No of controls; gender; age	Assay method, sample type, fasting status	Exposure vs reference category	Matching factors	Adjusting factors
Kim et al[10]	Case-control	Patients who underwent colonoscopy and/or patients who underwent screening colonoscopy	631; 242; M and F > 30 yr	CRP (ELISA), IL-6 (ELISA), TNF-α (ELISA), plasma, fasting	T3 (≥ 12013.1 ng/mL) vs T1 (< 2916.03 ng/mL) for CRP; T3 (≥ 0.3571 pg/mL) vs T1 (0 pg/mL) for IL-6; T3 (≥ 2.2358 pg/mL) vs T1 (< 1.3877 pg/mL) for TNF-α	NA	Age, sex, obesity
Tsilidis et al[11]	Nested case-control	Subjects who undergone sigmoidoscopy or colonoscopy	269; 135, M and F 45-65 yr	CRP (Dade-Behring method), plasma, NR	Q4 (> 2.95 mg/L) vs Q1 (< 0.65 mg/L)	Age, sex, race, date of blood draw, time since last meal, type of endoscopy	Cigarette smoking status, BMI at baseline, BMI at age 21, ever use of estrogen or progesterone (women), use of aspirin or non-steroidal anti-inflammatory drugs, use of diabetes medications, family history of colorectal cancer
Otake et al[12]	Case-control	Subjects who underwent colonoscopy for health checkup	635; 646; M 50-53 yr	CRP(INA), plasma/serum, fasting	Q4 (≥ 1541 ng/mL) vs Q1 (< 206 ng/mL)	NA	Age, hospital, plasma/serum status, rank in the Self Defense Forces, cigarette smoking, alcohol use, BMI, physical activity, parental colorectal cancer
Ognjanovic et al[13]	Case-control	Subjects who undergone screening sigmoidoscopy	539; 271; M and F 55-69 yr	CRP (ITA), IL-6 (ELISA), serum, fasting	Q4 (> 2.00 mg/L) vs Q1 (> 0.30 mg/L) for CRP; Q4 (> 2.79 pg/mL) vs Q1 (> 1.09 pg/mL) for IL-6	Age, sex, ethnicity, screening date, recruitment clinic	Sex, age, race, smoking status, BMI
Otake et al[14]	Cross-sectional	Patients who underwent colonoscopy	26; 47; M 53-80 yr	CRP (INA), plasma, fasting	high (≥ 500 ng/mL) vs low (< 500 ng/mL)	NA	None
Yamaji et al[15]	Case-control	Healthy subjects who underwent screening colonoscopy	735; 778; M 50-79 yr; F 40-79 yr	TNF-α (Cytokine/Chemokine Magnetic Bead Panel Assay), plasma, fasting	Q3 (≥ 2.98 pg/mL) vs Q1 ( ≤ 2.38 pg/mL)	Age, two screening periods	Age, sex, screening period, duration of fasting, cigarette smoking, alcohol drinking, family history of colorectal cancer, nonsteroidal anti-inflammatory drug use, BMI
Gunter et al[16]	Nested case-control	Subjects who undergone screening sigmoidoscopy	396; 356; M and F 55-74 yr	CRP (Chemiluminescent Immunometric Assay), serum, NR	Q4 (≥ 4.0 mg/L) vs Q1 (< 0.8 mg/L)	Age at study entry, gender, fiscal year at study entry, race, screening center, study protocol, season of blood draw	Cigarette smoking status, BMI, use of non-steroidal anti-inflammatory drugs, diabetes, use of hormone therapy (females only), family history of colorectal cancer, educational attainment
Sasaki et al[17]	Case-control	Subjects who underwent colonoscopy for health checkup	218; 118; M 52 yr cases, 51 yr controls (median)	IL-6 (ELISA), serum, fasting	Q4 (≥ 1.619 pg/mL) vs Q1 (< 0.804 pg/mL)	Age	Age, current smoking, alcohol consumption, family history of CRC, BMI, HOMA-IR, insulin
Vaughn et al[18]	Case-control	Patients who underwent routine colonoscopy	1050; 401; M and F 46-66 yr	IL-6 (ELISA), TNF-α (Cytokine/ Chemokine Magnetic Bead Panel Assay), serum, fasting	T3 (> 2.71 pg/mL) vs T1 (< 1.44 pg/mL) for IL-6; T3 (> 4.46 pg/mL) vs T1 (< 3.01 pg/mL) for TNF-α	NA	Age, sex, non-steroidal anti-inflammatory use, BMI, family history of colorectal cancer, smoking status, race
Kong et al[19]	Case-control	Patients who underwent colonoscopy	201; 139; M and F 46-66 yr	CRP (INA), plasma, NR	high (> 6.2 mikrog/mL) vs low (< 6.2 mikrog/mL)	NA	Age, race, sex, BMI, total energy intake, plasma cholesterol, family history of colorectal cancer in a first degree relative, hormone replacement therapy, dietary fiber, physical activity, study
Basavaraju et al[20]	Case-control	Patients who undergone screening colonoscopy	319; 50; M and F 64 yr	CRP (INA), IL-6 (Cytometric Bead Array), TNF-α (Cytometric Bead Array), serum (CRP), plasma (IL-6, TNF-α), fasting	high (> 1.88) vs low ( ≤ 1.88) units NR for CRP; high (> 3.32) vs low ( ≤ 3.32) units NR for IL-6; high (> 3.53) vs low ( ≤ 3.53) units NR for TNF-α	NA	Time of recruitment, age, sex, BMI, alcohol consumption, exercise, smoking, diverticular disease, exercise, aspirin use
Davenport et al[21]	Case-control	Patients who underwent colonoscopy	395; 707; M and F 49-67 yr	CRP (ITA), plasma, NR	single small tubular adenoma T3 (> 5.97 mg/L) vs T1 (< 1.59 mg/L); multiple small tubular adenoma T3 (> 6.96 mg/L) vs T1 (< 1.82 mg/L); advanced adenoma T3 (> 7.16 mg/L) vs T1 (< 1.69 mg/L)	Age, sex, race, and matched at least one of the following factors: study site, collection date of plasma, NSAID use for a minimum of three times per week for at least one year	Age, educational attainment, study site
Henry et al[22]	Nested case-control	Subjects who undergone colonoscopy	97; 97; M and F ≥ 50 yr	IL-6 (Cytokine/Chemokine Magnetic Bead Panel Assay), TNF-α (Cytokine/Chemokine Magnetic Bead Panel Assay), serum, fasting	T3 vs T1 for IL-6; T3 vs T1 for TNF-α	NA	Age, sex, previous screening
Song et al[23]	Nested case-control	Subjects who undergone sigmoidoscopy or colonoscopy	757; 757; F 30-55 yr	CRP (ITA), IL-6 (ELISA), plasma, fasting/non-fasting	Q5 (6.32 mg/L - median) vs Q1 (0.43 mg/L - median) for CRP; Q5 (2.64 ng/l - median) vs Q1 (0.42 ng/l - median) for IL-6	Date of endoscopy, birth year, indication for endoscopy, time period of any prior endoscopy, month and year of blood draw, fasting status	Family history of colorectal cancer, multivitamin use, pack-years of smoking before age 30, alcohol consumption, BMI, physical activity, regular aspirin/NSAID use, postmenopausal status and hormone use, calcium intake, and Alternative Healthy Eating Index

BMI: Body mass index; ELISA: Enzyme-linked immunosorbent assay; NA: Not applicable; NR: Not reported; 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.