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Table 3 Summary of observational studies on the association between ARA and risk of breast cancer

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

References Study Subjects Exposure Assessment Breast 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
Holmes et al. 1999 [51] NHS, USA, 1976- 1994, prospective cohort design (14 year biennial follow-up, follow-up rate = 95%) 88,795 female nurses aged 30-55, no prior history of cancer other than nonmelanoma skin cancer Semiquantitative FFQ, 131 items, validated against 2 x 7-day WR Self-reported physician diagnosis, deaths identified by family member of participants, postal services and National Death Index, supplemented by medical record Total energy intake, age, energy-adjusted vitamin A intake, alcohol intake, time period, height, parity, age at first birth, weight change, BMI, age at menopause, menopausal status, use of HRT, family history, benign breast disease, age at menarche 19 %energy increment of dietary ARA intake per day 0.03 RR(95% CI) P
1.05(1.00-1.10) Not shown
Study design: nested case-control study
Exposure assessment: dietary intake
Voorrips et al. 2002 [52] NLCS, Netherlands, 1986-1992 (6.3 years follow-up), case-cohort design 941 breast cancer patients from entire cohort, 1,598 subcohort members (selection criteria not shown), aged 55-69 at baseline, no prior history of cancer other than nonmelanoma skin cancer, matching not indicated Semiquantitative FFQ, 150 items, validated against 3 x 3-day DR All regional cancer registries and Dutch national database of pathology reports Age, history of benign breast disease, maternal breast cancer, breast cancer in one or more sisters, age at menarche, age at menopause, oral contraceptive use, parity, age at first birth, Quetelet index, educational level, alcohol intake, smoking status, total energy intake, total energy-adjusted fat intake 19 Dietary ARA intake, g/day, quintile, median RR(95%CI) Ptrend
Q1: 0.05 1.00 0.93
Q2: 0.07 0.80(0.59-1.07)
Q3: 0.09 0.84(0.63-1.13)
Q4: 0.11 0.80(0.59-1.08)
Q5: 0.15 0.99(0.73-1.34)
Exposure assessment: blood ARA level
Saadatian-Elahi et al. 2002 [29] NYUWHS, USA, 1985-1995 (average 4.3 years follow-up), nested case-control design 197 breast cancer patients, 197 controls (free of cancer), aged 34-65, matched by age, menopausal status, date of blood sampling, number of blood samplings, day of menstrual cycle Serum phospholipids, GC analysis, precision indicated Self-reported physician diagnosis, combined with tumor registries, mortality databases and review of clinical and pathological documents Family history, age at first full-term birth, total cholesterol, history of treatment for benign breast conditions 19 ARA composition%, quartile OR(95% CI) P for the overall categorial variable:
Q1 1.00 0.80
Q2 0.79(0.43-1.46)  
Q3 0.99(0.55-1.81) Ptrend with the score variable
Q4 0.81(0.45-1.47) 0.66
Pala et al. 2001 [53] ORDET study, Italy, 1987-1995 (average 5.5 years follow-up) 71 breast cancer patients, 141 controls (free of cancer), 1 case matched with 2 controls by age, menopausal status at recruitment, daylight-saving period at blood sampling, recruitment center and date Erythrocyte phospholipids (fasting blood), GC analysis blinded to case-control status, precision indicated Lombardy Cancer Registry None (BMI, WHR, age at menarche, age at first birth, age at menopause, months of lactation, parity and educational level were investigated) 23 ARA composition%, tertile OR(95%CI) Ptrend
T1: <16.67 1.00 0.42
T2: ≥16.67- 1.76(0.88-3.53)
<17.94 1.40(0.64-3.10)
T3: ≥17.94  
Chajès et al. 1999 [54] Three ongoing cohort studies in Sweden, VIP(1986- 1997), northern Sweden component of the WHO MONICA(1986, 1990 and 1994), MSP(1995-1997), nested case-control design 196 breast cancer patients (VIP 103, MONICA 9, MSP 84), 388 controls (VIP 214, MONICA 6, MSP 168), 1 case matched with 2 controls by age, age of blood sample, sampling center Serum phospholipids (for VIP and MONICA fasting blood, for MSP very little fasting blood), GC analysis, precision indicated Regional cancer registry, National Cancer Registry, follow-up for vital status (death) or losses to follow-up determined through local and national population registries Age at menarche, parity, age at first full-term pregnancy, use of hormones, menopausal status 19 ARA composition%, quartile OR(95%CI) Ptrend
Q1 1.00 0.091
Q2 0.49(0.24-0.99)
Q3 0.48(0.22-1.04)
Q4 0.51(0.24-1.09)
Study design: case-control study (temporal relationship among exposure and outcome is demonstrated)
Exposure assessment: dietary intake
Nkondjock et al. 2003 [55] Survey, Canada, 1989-1993, case-control design 414 primary breast cancer patients aged 35-79, 688 controls (eligibility criteria not shown), population-based, matched by age, language, place of residence French version FFQ, >200 items, validated against 7-day FD Histological diagnosis Age at first full-term pregnancy, smoking status, family history of breast cancer, history of benign breast disease, marital status, number of full-term pregnancies, total energy intake 20 Dietary ARA intake, g/day, quartile OR(95%CI) Ptrend
Q1 1.00 0.723
Q2 0.65(0.44-0.97)
Q3 1.01(0.70-1.53)
Q4 0.86(0.58-1.30)
Exposure assessment: blood ARA level
Vatten et al. 1993 [56] Janus Serum Bank, Norway, 1973-1991, case-control design 87 breast cancer patients, 235 controls with no prior history of cancer, matched by age, date of blood sampling Serum phospholipid, GC analysis blinded to case-control state, precision indicated National cancer registry linked to Janus Serum Bank donor information None 20 ARA concentration, mg/l, mean(SD) 78(30) ARA concentration, mg/l, mean(SD) 79(29) P
Not significant
Exposure assessment: tissue ARA level
London et al. 1993 [57] Survey, USA, 1986-1988, case-control design Postmenopausal women, 380 breast cancer patients, 573 controls with breast abnormality (free of breast cancer), matching not indicated Buttock adipose tissue fatty acids, GC analysis, precision indicated Physician diagnosis (detail not shown) Age, alcohol intake, age at first birth, parity, family history of breast cancer, age at menopause, age at menarche, history of benign breast disease, weight 19 ARA composition%, quintile OR(95% CI) Ptrend
Q1 1.0 0.60
Q2 0.8(0.5-1.2)
Q3 0.9(0.6-1.5)
Q4 1.0(0.6-1.6)
Q5 1.0(0.6-1.6)
Study design: case-control study (temporal relationship among exposure and outcome is unclear)
Exposure assessment: dietary intake
Zhu et al. 1995 [58] Survey, Finland, 1990-1992 17 premenopausal, 32 postmenopausal primary breast cancer patients, 34 premenopausal, 16 postmenopausal controls with benigh breast disease (eligibility criteria not shown), matching not indicated Semiquantitative FFQ, 110 items, validated against 14-day DR Histological diagnosis Age, total energy intake 13 Dietary ARA intake, mg/day, mean(SD) Dietary ARA intake, mg/day, mean(SD) P
Premenopausal case: Premenopausal control: Premenopausal:
58(27) 163(323) Not significant
Postmenopausal case: Postmenopausal control: Postmenopausal:
90(191) 62(26) Not significant
Exposure assessment: blood ARA level
Aro et al. 2000 [59] Kuopio Breast Cancer Study, Finland, 1992-1995, case-control design 195 primary breast cancer patients aged 25-75, 208 controls drawn randomly from the National Population Register, matched by age, long-term area of residence Serum fatty acids (fasting blood), GC analysis, precision indicated Histological diagnosis Age, area, age at menarche, age at first full-term pregnancy, use of oral contraceptives, use of HRT, family history of breast cancer, history of benign breast disease, educational level, alcohol intake, smoking status, physical activity, WHR, BMI 15 ARA composition%, quintile, median OR(95% CI) Ptrend
Postmenopausal: Postmenopausal: Postmenopausal:
Q1: 3.84 1.0 Signifncant
Q2: 4.89 1.1(0.4-2.8)
Q3: 5.46 2.0(0.8-4.8)
Q4: 6.04 2.4(1.0-5.9)
Q5: 7.15 3.1(1.3-7.8)
ARA composition%, mean(SD) ARA composition%, mean(SD) P
Premenopausal case: Premenopausal control: Premenopausal:
5.68(1.01) 5.49(1.16) Not significant
Zaridze et al. 1990 [60] Survey, now-defunct Union of Soviet Socialist Republics, case-control design 25 premenopausal, 21 postmenopausal primary breast cancer patients, 20 premenopausal, 33 postmenopausal neighborhood controls (eligibility criteria not shown), matching not indicated Erythrocyte phospholipids (fasting blood), GC analysis, precision not indicated Not shown None 11 ARA concentration, μg/mg phospholipids, bisectional, (Summer-Autumn/Winter-Spring) RR(95%CI) P
Premenopausal: Premenopausal: Premenopausal:
≤11.70/9.89 vs 0.33(0.08-1.35) 0.122
>11.70/9.89
Postmenopausal: Postmenopausal: Postmenopausal:
≤11.70/9.89 vs 0.23(0.07-0.78) 0.018
>11.70/9.89
Exposure assessment: tissue ARA level
Bagga et al. 2002 [61] Survey, USA, 1995-1996, case-control design 73 breast cancer patients, 73 controls undergoing reduction mammoplasty for mastomegaly, matching not indicated Breast adipose tissue fatty acids, GC analysis, precision not indicated Not shown None 15 ARA concentration, μmol/g total fatty acid, mean(SEM) ARA concentration, μmol/g total fatty acid, mean(SEM) P
Case: Control: 0.27
15.03(1.20) 13.13(1.25)
Maillard et al. 2002 [62] Survey, France, 1992-1996, case-control design 241 patients with non-metastatic invasive breast carcinoma, 88 controls with benign breast diseases, matching not indicated Breast adipose tissue triglycerides, GC analysis blinded to case-control status, precision indicated Not shown Age at diagnosis, height, BMI, menopausal status, BMI-menopausal status interaction 16 ARA composition%, tertile OR(95% CI) Ptrend
T1 1.00 0.32
T2 0.87(0.41-1.84)
T3 0.98(0.42-2.29)
Zhu et al. 1995 [58] Survey, Finland, 1990-1992 26 premenopausal, 47 postmenopausal primary breast cancer patients, 35 premenopausal, 20 postmenopausal controls with benign breast disease (eligibility criteria not shown), matching not indicated Breast adipose tissue triglycerides and phospholipids, GC analysis, precision not indicated Histological diagnosis Age 13 Triglyceride ARA composition mol%, mean(SD) Triglyceride ARA composition mol%, mean(SD) P
Premenopausal case: Premenopausal control: Triglyceride
0.33(0.18) 0.33(0.27) Premenopausal:
Postmenopausal case: Postmenopausal control: Not significant
0.33(0.18) 0.55(0.62) Postmenopausal:
Phospholipid ARA composition mol%, mean(SD), Premenopausal case: Phospholipid ARA composition mol%, mean(SD), Premenopausal control: <0.01
9.67(2.56) 9.58(2.17) Phospholipid
Postmenopausal case: Postmenopausal control: Premenopausal:
9.64(2.26) 10.95(3.26) Not significant
Postmenopausal:
Not significant
Petrek et al. 1994 [63] Survey, USA, 1987-1989, case-control design 154 invasive breast cancer patients, 125 controls at average risk of breast cancer, matching not indicated Breast adipose tissue fatty acids, GC analysis, precision not indicated Histological diagnosis None 7 ARA composition weight%, mean(SD) ARA composition weight%, mean(SD) P
Case: Control: Not significant
0.40(0.15) 0.39(0.16)
Study design: cross-sectional study
Exposure assessment: blood ARA level
Williams et al. 1993 [64] Survey, UK 12 malignant breast disease patients, 10 benign breast disease patients, 22 normal controls Erythrocyte PIs and PCs (fasting blood), GC analysis, precision not indicated Histological diagnosis None 8 ARA composition%, only shown as figure: P
Erythrocyte PIs: not significant PCs:
Erythrocyte PCs: significantly higher in control compared with benign and malignant group Malignant/Control:
<0.02
Benign/Control:
<0.02
Hietanen et al. 1994 [46] Survey, UK, cross-sectional design 20 breast cancer patients aged 37-85, controls matched by age, sex, smoking status Erythrocyte phospholipids (fasting blood), GC analysis, precision not indicated Not shown None 10 ARA composition%, mean(SD) ARA composition%, mean(SD) P
Case: Control: Not significant
17.5(0.8) 18.5(1.5)
Punnonen et al. 1989 [65] Survey, Finland 6 breast cancer patients, 9 normal controls Erythrocyte phospholipids, GC analysis, precision not indicated Histological diagnosis None 5 ARA composition%, mean(SEM) ARA conposition%, mean(SEM) P
Case: Control: Not significant
12.1(1.5) 13.3(0.9)
Exposure assessment: tissue ARA level
Williams et al. 1993 [64] Survey, UK 12 malignant breast disease patients, 10 benign breast disease patients, 6 normal controls Breast tissue PIs and PCs, GC analysis, precision not indicated Histological diagnosis None 8 ARA composition%, only shown as figure: P
Breast tissue PIs: not significant PCs:
Breast tissue PCs: significantly higher in control compared with benign and malignant group Malignant/Control:
<0.02
Benign/Control:
<0.02
Eid et al. 1988 [66] Survey, Israel 85 sequential patients (37 carcinoma, 27 fibroadenoma, 21 others) Breast adipose tissue fatty acids, GC analysis, precision indicated Not shown None 8 ARA composition%, mean(SD) ARA composition, mean(SD) P
Carcinoma: Others: Not significant
0.62(0.05) 0.46(0.04)
Fibroadenoma:
0.78(0.18)
  1. ARA Arachidonic acid, BMI Body mass index, DR Diet record, FD Food record, FFQ Food frequency questionnaire, GC Gas chromatography, HRT Hormone replacement therapy, MONICA multinational study for Monitoring of Trends and Cardiovascular Disease study, MSP Mammary-Screening Project, NHS Nurses' Health study, NLCS Netherlands Cohort Study on Diet and Cancer, NYUWHS New York University Women's Health Study, OR Odds ratio, ORDET study: the Hormones and Diet in the Etiology of Breast Cancer Risk study, PC Phosphatidyl-choline, PI Phosphatidyl-inositol, RR Relative risk, UK United Kingdom, USA United States of America, VIP Västerbotten Intervention Project, WHR Waist-to-hip ratio, WR Weighed dietary record.
  2. *Result of the critical evaluation carried out using the STROBE tool.