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Table 1 Summary of observational studies on the association between ARA and risk of colorectal cancer

From: Arachidonic acid and cancer risk: a systematic review of observational studies

References Study Subjects Exposure Assessment Colorectal cancer assessment (diagnosis) Adjustment for potential confounders Assessment of reporting quality * Main findings
Intergroup comparison   P or Ptrend
Study design: cohort study
Exposure assessment: dietary intake
Murff et al. 2009 [30] SWHS, China, 1996-2007, prospective cohort design (7-year biennial follow-up, follow-up rate = 96.7%) 73,243 women aged 40-70, no prior history of cancer SWHS's FFQ, 77 items, previously validated against 24 x 24-HDR Self-reported physician diagnosis, combined with annual record linkage with the Shanghai Cancer Registry and Shanghai Vital Statistics database Age at baseline, total energy intake, smoking status, alcohol intake, physical activity, energy-adjusted total red meat consumption, menopausal status, use of HRT, multivitamin, aspirin, total n-3 PUFA intake, n-6 to n-3 PUFA ratio 18 Dietary ARA intake, g/day, quintile, median RR (95%CI) Ptrend
Q1: 0.02 1.00 0.03
Q2: 0.03 1.20 (0.87-1.64)
Q3: 0.05 1.44 (1.05-1.98)
Q4: 0.06 1.61 (1.17-2.23)
Q5: 0.09 1.39 (0.97-1.99)
Lin et al. 2004 [28] WHS, USA, 1993–2003, prospective cohort design nested randomized, double-blind, placebo-controlled 2 × 2 factorial aspirin and vitamin A trial (average 8.7 years follow-up) 37,547 female health professionals aged ≥45, free of heart disease and cancer except NMSC FFQ, 131 items, validated against 2 x 7-day WR Self-reported physician diagnosis, reviewed and confirmed medical diagnoses Age, treatment assignment, BMI, family history of CRC, colorectal polyps, physical activity, smoking status, alcohol intake, use of HRT, total energy intake 15 Dietary ARA intake, %energy, quintile, median RR (95%CI) Ptrend
Q1: 0.04 1.00 0.55
Q2: 0.06 0.86 (0.57-1.32)
Q3: 0.07 0.84 (0.55-1.28)
Q4: 0.09 0.73 (0.47-1.14)
Q5: 0.12 0.90 (0.59-1.36)
Study design: nested case-control study
Exposure assessment: blood ARA level
Hall et al. 2007 [34] PHS, USA, 1982-1995, nested case-control design within a randomized, double-blind, placebo-controlled factorial aspirin and beta-carotene trial (average 5 and 7 years follow-up) 178 CRC patients, 282 controls, male physicians without history of cancer aged 40-84 years at baseline, 1 case matched with 1-2 controls by age, smoking status Whole blood fatty acids, GC analysis blinded to case-control status at a time, precision indicated Self-report, combined with review of medical records None 23 ARA composition%, geometric mean(95%CI) Case: ARA composition%, geometric mean(95%CI) Control: P
9.77(9.57-9.99) 9.93(9.77-10.10) Not significant
Kojima et al. 2005 [35] JACC Study, Japan, 1988-1997, nested case-control design (7 years follow-up) 169 primary CRC patients, 481 controls without previous history of cancer, aged 40-79 years at baseline, 1 case matched with 2-3 controls by age, sex, resident area Serum fatty acids, GC analysis blinded to case-control status, precision not indicated Population-based cancer registries, supplemented by death certificates Age at completing final education, family history of CRC, BMI, smoking status, alcohol intake, intake of green leafy vegetables, physical activity 23 ARA composition, weight % of total serum lipids, quartile OR (95%CI) P trend
Men: Men: Men:
Q1: <3.71 1.00 0.99
Q2: 3.71-4.619 1.24 (0.55-2.78)
Q3: 4.62-5.269 0.79 (0.32-1.96)
Q4: ≥5.27 1.16 (0.49-2.75)
Women: Women: Women:
Q1: <4.20 1.00 0.40
Q2: 4.20-4.879 0.67 (0.31-1.46)
Q3: 4.88-5.634 0.49 (0.22-1.10)
Q4: ≥5.635 0.65 (0.30-1.44)
Study design: case-control study (temporal relationship among exposure and outcome is demonstrated)
Exposure assessment: dietary intake
Theodoratou et al. 2007 [36] Survey, UK, 1999-2006, case-control design 1,455 primary CRC patients aged 16-79, 1,455 controls (eligibility criteria not shown), matched by age, sex, resident area Scotish FFQ, 150 items, validated against 4-day WR, (response rate = case 82%, control 97%) Not shown Family history of CRC, total energy intake, total fiber intake, alcohol intake, NSAIDs use, smoking status, BMI, physical activity, total fatty acid intake 20 Dietary ARA intake, mg/day, quartile OR (95%CI) Ptrend
Q1: 0-5.82 1.00 0.163
Q2: 5.83-8.40 1.09 (0.87-1.37)
Q3: 8.41-11.34 0.79 (0.63-1.01)
Q4:≥11.35 0.93 (0.72-1.19)
Nkondjock et al. 2003 [31] Survey, Canada, 1989-1993, case-control design 402 CRC patients aged 35-79, 688 controls, matched by age, language, place of residence FFQ, 132 items, validated against 7-day Food Record Histological diagnosis Age, BMI, family history of CRC, marital status, physical activity 20 Dietary ARA intake, g/day, quartile OR (95% CI) Ptrend
Q1:<0.06 1.00 0.001
Q2:0.06-0.09 1.24 (0.84-1.84)
Q3:0.10-0.14 1.64 (1.12-2.40)
Q4:>0.14 2.11 (1.47-3.06)
Slattery et al. 1997 [37] Survey, USA, 1991-1994 1993 CRC patients aged 30-79, 2410 controls without history of CRC (population characteristic partially not shown), matched by age, sex, resident state CARDIA Diet History Questionnaire, validated against 7 x 24-HDR Cancer registries Total energy intake, age at selection, BMI, family history of CRC, physical activity, dietary cholesterol, calcium, fiber, NSAIDs use 19 Dietary ARA intake, g/MJ, quintile OR (95%CI) Ptrend
Men: Men: Men:
Q1:<0.17 1.00 Not shown
Q2:0.17-0.22 1.25 (0.95-1.65)
Q3:0.23-0.26 1.08 (0.81-1.44)
Q4:0.27-0.33 1.37 (1.03-1.83)  
Q5:>0.33 1.17 (0.85-1.61)  
Women: Women: Women:
Q1:<0.039 1.00 Not shown
Q2:0.039-0.051 0.99 (0.73-1.33)  
Q3:0.052-0.063 1.15 (0.86-1.55)  
Q4:0.064-0.077 0.98 (0.72-1.35)  
Q5:>0.077 0.98 (0.70-1.37)  
Exposure assessment: blood ARA level
Kuriki et al. 2006 [38] Survey, Japan, 2002-2004, case-control design 74 CRC patients, 221 controls, aged 20-80 without history of cancer or current diseases, 1 case matched with 3 controls by age, sex, season of blood collection Erythrocyte phospholipids, GC analysis blinded to case-control status, precision indicated Histological diagnosis BMI, habitual exercise, alcohol intake, smoking status, green-yellow vegetable intake, family history of CRC 22 ARA composition, mol%, tertile OR (95% CI) Ptrend
T1: <8.625 1.00 <0.05
T2: 8.625-10.178 0.91 (0.48-1.73)
T3: >10.178 0.42 (0.18-0.95)
Study design: case-control study (temporal relationship among exposure and outcome is unclear)
Exposure assessment: dietary intake
Busstra et al. 2003 [39] Survey, Netherlands, 1995-1998, case-control design 52 CRC patients, 57 controls, aged under 75 without history of CRC, colon resection, polyposis coli, inflammatory bowel disease, included subjects with familial HNPCC, matching not indicated FFQ developed for the Dutch cohorts of the EPIC study, 178 items, validated against 12 x 24-HDR Histological diagnosis Age, total energy intake, sex, familial background of HNPCC 13 Dietary ARA intake, g/day, tertile OR (95% CI) Ptrend
T1: <0.02 1.0 0.37
T2: 0.02-0.04 1.3 (0.4-3.9)
T3: ≥0.04 0.6 (0.2-1.8)
Exposure assessment: blood ARA level
Ghadimi et al. 2008 [40] Survey, Japan, 1997-2003, case-control design 203 CRA patients, 179 controls (negative faecal occult blood test), matching not indicated Serum fatty acids (fasting blood), GC analysis, precision indicated Histological diagnosis Age, BMI, family history of CRA or CRC, history of diabetes, smoking status, alcohol intake, physical activity, season of data collection 18 ARA concentration, mg/dl, quartile OR (95%CI) Ptrend
Men: Men: Men:
Q1:<17.40 1.00 0.104
Q2:17.40-19.90 0.60 (0.21-1.68) Women:
Q3:19.91-22.50 0.58 (0.21-1.60) 0.001
Q4:>22.50 0.52 (0.19-1.42)  
Women: Women: Women:
Q1:<18.05 1.00 0.001
Q2:18.05-20.50 0.49 (0.19-1.24)  
Q3:20.51-22.38 0.11 (0.28-0.45)  
Q4:>22.38 0.11 (0.03-0.43)  
Baró et al. 1998 [41] Survey, Spain 17 CRC patients aged 35-82, 12 controls aged 33-81 with no malignant diseases, matched by age, resident area Plasma and erythrocyte fatty acids (fasting blood), GC analysis, precision not indicated Not shown None 12 Plasma ARA concentration, mg/dl, mean(SEM) Plasma ARA concentration, mg/dl, mean(SEM) P
Case: Control: Plasma:
18.59(1.31) 21.31(1.22) Not significant
Erythrocyte ARA composition%, mean(SEM) Erythrocyte ARA composition%, mean(SEM) Erythrocyte:
Case: Control: Not significant
14.61(0.24) 13.50(0.40)
Neoptolemos et al. 1990 [42] Survey, UK 32 CRC patients, 42 controls admitted for elective operations for benign without DM, metabolic disorders, blood transfusions, matched by age, sex, admittance period Erythrocyte phospholipids (fasting blood), GC analysis, precision not indicated Not shown None 13 ARA composition%, median(range) ARA composition%, median(range) P
Case: Control:  
20.7(12.8-48.9) 18.0(0.0-47.3) Not significant
Neoptolemos et al. 1988 [43] Survey, UK 49 CRC patients aged 49-92, 49 controls with benign diaseases aged 48-90, matched by age, sex Erythrocyte phospholipids (fasting blood), GC analysis, precision not indicated Not shown None 12 ARA composition%, median(range) ARA composition%, median(range) P
Case: Control:  
21.8 (15.3-28.4) 23.5 (13.8-32.8) 0.043
Exposure assessment: tissue ARA level
Busstra et al. 2003 [39] Survey, Netherlands, 1995-1998, case-control design 52 CRC patients, 57 controls, aged under 75 without history of CRC, colon resection, polyposis coli, inflammatory bowel disease, included subjects with familial HNPCC, matching not indicated Buttock adipose tissue fatty acids, GC analysis, precision not indicated Histological diagnosis Age, total energy intake, sex, familial background of HNPCC 13 ARA composition mass%, tertile OR(95%CI) Ptrend
T1: <0.35 1.0 0.42
T2: 0.35-0.45 2.6 (0.7-8.5)
T3: ≥0.45 1.7 (0.5-5.8)
Study design: cross-sectional study
Exposure assessment: blood ARA level
Almendingen et al. 2006 [44] Survey, Norway 38 FAP patients aged 24-70 (all colectomized), 160 healthy controls aged 21-66 Serum phospholipids (fasting blood), GC analysis, precision indicated Diagnosis by endoscopy and histology None 17 ARA composition weight%, mean(SD) ARA composition weight%, mean(SD) P
Case: Control:  
10.96(1.85) 7.26(1.51) ≤0.0001
Fernández-Bañares et al. 1996 [45] Survey, Spain 22 colonic cancer patients, 27 colonic adenoma patients, 12 controls with benign diseases, no significant differences in sex and age Plasma phospholipids (fasting blood), GC analysis, precision not indicated Total fibreoptic colonoscopy None 13 ARA composition%, mean(SEM) Carcinoma: ARA composition%, mean(SEM) Controls: P
9.38(0.37) 10.2(0.32) Not significant
Adenoma:  
9.95(0.49)  
Hietanen et al. 1994 [46] Survey, UK, cross-sectional design 20 colon cancer patients aged 38-84, controls, matched by age, sex, smoking status Erythrocyte phospholipids (fasting blood), GC analysis, precision not indicated Not shown None 8 ARA concentration, mg/dl, mean(SD) ARA concentration, mg/dl, mean(SD) P
Case: Control:  
18.5(0.6) 20.2(0.5) <0.05
Exposure assessment: tissue ARA level
Fernández-Bañares et al. 1996 [45] Survey, Spain 15 colonic cancer patients, 21 colonic adenoma patients, 8 controls with benign diseases Normal colon mucosa fatty acids, GC analysis, precision not indicated Total fibreoptic colonoscopy None 13 ARA composition%, mean(SEM) Carcinoma: ARA composition%, mean (SEM) Controls: P
10.9(0.57) 11.4 (0.88) Not significant
Adenoma:  
12.3(0.55)  
Berry et al. 1986 [47] Survey, Israel, 1982-1985 155 consecutive colonoscopies (53 carcinoma, 34 benign neoplastic polyps, 68 controls) Buttock adipose tissue fatty acids, GC analysis, precision indicated Histological diagnosis None 13 ARA composition%, mean (SD) Carcinoma: ARA composition%, mean (SD) Controls: P
0.54 (0.2) 0.55 (0.2) Not significant
Benign neoplastic polyps:  
0.52 (0.2)
  1. 24-HDR 24-h dietary recall, ARA Arachidonic acid, BMI Body mass index, CRA Colorectal adenoma, CRC Colorectal cancer, DM Diabetes mellitus, FAP Familial adenomatous polyposis, FFQ Food frequency questionnaire, GC Gas chromatography, HNPCC Hereditary non-polyposis colorectal cancer, HRT Hormone replacement therapy, JACC Japan Collaborative Cohort, NMSC Nonmelanoma skin cancer, NSAIDs Nonsteroidal antiinflammatory drugs, OR Odds ratio, PHS Physician's health study, RR Relative risk, SWHS Shanghai Women's Health Study, UK United Kingdom, USA United States of America, WHS Women's Health Study, WR Weighed dietary record.
  2. *Result of the critical evaluation carried out using the STROBE tool.