Table 3.

Association of arachidonic acid and linoleic acid–derived metabolites and risk of overall ovarian cancer and histologic subtypes (serous and nonserous) of ovarian cancer in a nested case–control study in the PLCO Cancer Screening Trial

ControlCasesOverall casesSerous casesNonserous cases
Metabolites (pg/ml)N (%)N (%)ORa (95% CI)aN (%)OR (95% CI)N (%)OR (95% CI)P-Hetb
Alpha-linoleic acid derived
17,18-EpETEc
 0152 (97.4)154 (98.1)1.00 (Reference)83 (100)1.00 (Reference)63 (95.5)1.00 (Reference)
 >0 (detectable)4 (2.6)3 (1.9)0.91 (0.19–4.42)3 (4.5)1.96 (0.39–9.92)
17,18-DiHETEd
 ≤1,356.6752 (33.3)41 (26.1)1.00 (Reference)25 (30.1)1.00 (Reference)16 (24.2)1.00 (Reference)
 >1,356.67–≤2,07051 (32.7)55 (35.0)1.27 (0.70–2.30)31 (37.4)1.04 (0.51–2.14)22 (33.3)1.41 (0.64–3.11)
 >2,07053 (34.0)61 (38.9)1.48 (0.81–2.70)27 (32.5)0.96 (0.46–2.03)28 (42.4)1.89 (0.86–4.15)0.55
Ptrende0.200.630.10
19,20-EpDPE
 ≤1,90052 (33.3)35 (22.3)1.00 (Reference)18 (21.7)1.00 (Reference)15 (22.7)1.00 (Reference)
 >1,900–≤3,448.3350 (32.1)66 (42.0)1.87 (1.03–3.39)34 (41.0)1.67 (0.79–3.52)31 (47.0)2.31 (1.07–4.97)
 >3,448.3354 (34.6)56 (35.7)1.42 (0.76–2.67)31 (37.4)1.26 (0.58–2.76)20 (30.3)1.43 (0.62–3.31)0.99
Ptrend0.320.650.39
19,20-DiHDPA
 ≤883.3352 (33.3)44 (28.0)1.00 (Reference)27 (32.5)1.00 (Reference)17 (25.8)1.00 (Reference)
 >883.33–≤1,39051 (32.7)56 (35.7)1.45 (0.80–2.61)26 (31.3)1.04 (0.50–2.17)27 (40.9)1.84 (0.86–3.96)
 >1,39053 (34.0)57 (36.3)1.20 (0.65–2.19)30 (36.1)0.86 (0.41–1.81)22 (33.3)1.38 (0.62–3.10)0.77
Ptrend0.600.470.42
Linoleic acid/COX derived
9-HODEf
 ≤4,383.3352 (33.3)41 (26.1)1.00 (Reference)18 (21.7)1.00 (Reference)22 (33.3)1.00 (Reference)
 >4,383.33–≤7,45051 (32.7)48 (30.6)1.34 (0.72–2.48)30 (36.1)1.93 (0.88–4.24)15 (22.7)0.81 (0.36–1.83)
 >7,45053 (34.0)68 (43.3)1.97 (1.06–3.68)35 (42.2)2.39 (1.08–5.29)29 (43.9)1.42 (0.65–3.08)0.39
Ptrend0.030.060.36
9,10,13-THOME
 ≤2,153.3352 (33.3)35 (22.3)1.00 (Reference)18 (21.7)1.00 (Reference)15 (22.7)1.00 (Reference)
 >2,153.33–≤3,070.151 (32.7)62 (39.5)1.90 (1.02–3.53)35 (42.2)1.80 (0.83–3.88)24 (36.4)1.95 (0.85–4.45)
 >3,070.153 (34.0)60 (38.2)1.83 (1.02–3.66)30 (36.1)1.80 (0.81–4.00)27 (40.9)2.00 (0.88–4.58)0.81
Ptrend0.050.220.07
Linoleic acid/LOX derived
13-HODEf
 ≤4,50053 (34.0)36 (22.9)1.00 (Reference)17 (20.5)1.00 (Reference)17 (25.8)1.00 (Reference)
 >4,500–≤6,80050 (32.1)49 (31.2)1.71 (0.90–3.24)28 (33.7)2.11 (0.94–4.73)21 (31.8)1.55 (0.68–3.53)
 >6,80053 (34.0)72 (45.9)2.47 (1.32–4.60)38 (45.8)2.96 (1.34–6.56)28 (42.4)1.93 (0.86–4.34)0.51
Ptrend0.0050.010.12
9,12,13-THOMEf
 ≤913.3352 (33.3)35 (22.3)1.00 (Reference)21 (25.3)1.00 (Reference)12 (18.2)1.00 (Reference)
 >913.33–≤1,446.6751 (32.7)53 (33.8)1.61 (0.86–3.02)29 (34.9)1.22 (0.57–2.62)22 (33.3)2.18 (0.91–5.23)
 >1,446.6753 (34.0)69 (43.9)2.25 (1.20–4.21)33 (39.8)1.68 (0.78–3.61)32 (48.5)3.00 (1.28–7.03)0.29
Ptrend0.010.160.01
Linoleic acid/P450 derived
9,10-EpOME
 ≤6,95052 (33.3)58 (36.9)1.00 (Reference)33 (39.8)1.00 (Reference)21 (31.8)1.00 (Reference)
 >6,950–≤19,60051 (32.7)44 (28.0)0.77 (0.43–1.40)15 (18.1)0.48 (0.22–1.06)27 (40.9)1.22 (0.58–2.56)
 >19,60053 (34.0)55 (35.0)0.94 (0.53–1.65)35 (42.2)1.12 (0.57–2.19)18 (27.3)0.84 (0.39–1.81)0.63
Ptrend0.830.700.56
9,10-DHOME
 ≤2,956.6752 (33.3)32 (20.4)1.00 (Reference)17 (20.5)1.00 (Reference)14 (21.2)1.00 (Reference)
 >2,956.67–≤5,40051 (32.7)68 (43.3)2.15 (1.16–3.99)42 (50.6)2.17 (1.02–4.60)21 (31.8)1.86 (0.80–4.33)
 >5,40053 (34.0)57 (36.3)1.90 (0.98–3.67)24 (28.9)1.35 (0.58–3.11)31 (47.0)2.50 (1.06–5.90)0.15
Ptrend0.070.600.04
12,13-EpOME
 ≤23,05052 (33.3)46 (29.3)1.00 (Reference)17 (20.5)1.00 (Reference)27 (40.9)1.00 (Reference)
 >23,050–≤48,00050 (32.1)48 (30.6)1.16 (0.64–2.12)30 (36.1)2.23 (1.01–4.89)16 (24.2)0.63 (0.29–1.38)
 >48,00054 (34.6)63 (40.1)1.35 (0.75–2.44)36 (43.4)1.95 (0.90–4.22)23 (34.9)0.82 (0.39–1.73)0.05
Ptrend0.320.130.67
12,13-DHOMEf
 ≤3,226.6752 (33.3)30 (19.1)1.00 (Reference)16 (19.3)1.00 (Reference)13 (19.7)1.00 (Reference)
 >3,226.67–≤6,233.3351 (32.7)59 (37.6)2.08 (1.11–3.88)34 (41.0)2.11 (0.97–4.58)22 (33.3)1.83 (0.79–4.22)
 >6,233.3353 (34.0)68 (43.3)2.49 (1.29–4.81)33 (39.7)2.15 (0.95–4.87)31 (47.0)2.54 (1.07–6.04)0.52
Ptrend0.010.120.04
Arachidonic acid/COX derived
6-keto-PGF
 ≤1,138.3352 (33.3)48 (30.6)1.00 (Reference)25 (30.1)1.00 (Reference)20 (30.3)1.00 (Reference)
 >1,138.33–≤1,973.3350 (32.1)51 (32.5)1.33 (0.73–2.43)30 (36.1)1.58 (0.75–3.31)19 (28.8)1.09 (0.49–2.41)
 >1,973.3354 (34.6)58 (36.9)1.42 (0.77–2.62)28 (33.7)1.33 (0.62–2.86)27 (40.9)1.47 (0.67–3.24)0.38
Ptrend0.260.320.43
PGF
 ≤728.3352 (33.3)42 (26.8)1.00 (Reference)22 (26.5)1.00 (Reference)17 (25.8)1.00 (Reference)
 >728.33–≤2,075.0051 (32.7)64 (40.8)1.48 (0.82–2.65)32 (38.6)1.43 (0.69–2.95)28 (42.4)1.61 (0.75–3.45)
 >2,075.0053 (34.0)51 (32.5)1.07 (0.58–1.96)29 (34.9)1.02 (0.48–2.18)21 (31.8)1.24 (0.56–2.75)0.89
Ptrend0.860.910.60
PGE2
 ≤43.2852 (33.3)56 (35.7)1.00 (Reference)31 (37.4)1.00 (Reference)20 (30.3)1.00 (Reference)
 >43.28–≤124.6751 (32.7)46 (29.3)0.74 (0.41–1.34)22 (26.5)0.56 (0.27–1.19)22 (33.3)1.03 (0.47–2.24)
 >124.6753 (34.0)55 (35.0)0.95 (0.53–1.72)30 (36.1)0.86 (0.41–1.81)24 (36.4)1.22 (0.56–2.64)0.52
Ptrend0.870.660.63
PGD2c
 0124 (79.5)125 (79.6)1.00 (Reference)68 (81.9)1.00 (Reference)51 (77.3)1.00 (Reference)
 >0 (detectable)32 (20.5)32 (20.4)1.01 (0.56–1.84)15 (18.1)0.79 (0.37–1.67)15 (22.7)1.35 (0.63–2.88)0.08
TXB2
 ≤63.3351 (32.7)50 (31.8)1.00 (Reference)24 (28.9)1.00 (Reference)22 (33.3)1.00 (Reference)
 >63.33–≤1,35052 (33.3)54 (34.4)1.02 (0.56–1.84)31 (37.4)1.41 (0.68–2.93)20 (30.3)0.70 (0.32–1.53)
 >135053 (34.0)53 (33.8)1.08 (0.60–1.94)28 (33.7)1.28 (0.61–2.68)24 (36.4)1.04 (0.49–2.20)0.59
Ptrend0.810.490.94
Arachidonic acid/LOX derived
15-HETE
 ≤300.1752 (33.3)59 (37.6)1.00 (Reference)29 (34.9)1.00 (Reference)28 (42.4)1.00 (Reference)
 >300.17–≤448.3351 (32.7)35 (22.3)0.62 (0.34–1.12)20 (24.1)0.75 (0.36–1.58)11 (16.7)0.43 (0.19–0.98)
 >448.3353 (34.0)63 (40.1)1.18 (0.67–2.08)34 (41.0)1.31 (0.65–2.63)27 (40.9)1.08 (0.53–2.17)0.63
Ptrend0.550.500.88
12-HETE
 ≤2,888.3352 (33.3)56 (35.7)1.00 (Reference)28 (33.7)1.00 (Reference)24 (36.4)1.00 (Reference)
 >2,888.33–≤7,70051 (32.7)42 (26.8)0.75 (0.41–1.35)21 (25.3)0.78 (0.37–1.64)20 (30.3)0.80 (0.38–1.70)
 >7,70053 (34.0)59 (37.6)1.15 (0.65–2.02)34 (41.0)1.39 (0.69–2.79)22 (33.3)0.98 (0.47–2.04)0.37
Ptrend0.640.420.91
8-HETEf
 ≤3,581.6752 (33.3)43 (27.4)1.00 (Reference)18 (21.7)1.00 (Reference)24 (36.4)1.00 (Reference)
 >3,581.67–≤6,016.6751 (32.7)46 (29.3)1.36 (0.74–2.49)28 (33.7)2.60 (1.18–5.73)17 (25.8)0.75 (0.34–1.63)
 >6,016.6753 (34.0)68 (43.3)1.82 (1.01–3.26)37 (44.6)2.53 (1.18–5.39)25 (37.9)1.15 (0.56–2.36)0.10
Ptrend0.040.030.75
5-HETE
 ≤498.3352 (33.3)36 (22.9)1.00 (Reference)19 (22.9)1.00 (Reference)15 (22.7)1.00 (Reference)
 >498.33–≤780.0051 (32.7)69 (43.9)2.25 (1.24–4.07)35 (42.2)2.22 (1.06–4.65)30 (45.5)2.45 (1.13–5.31)
 >780.0053 (34.0)52 (33.1)1.59 (0.86–2.94)29 (34.9)1.72 (0.80–3.69)21 (31.8)1.60 (0.71–3.62)0.93
Ptrend0.180.160.27
LTB-4
 ≤78.8352 (33.3)40 (25.5)1.00 (Reference)20 (24.1)1.00 (Reference)16 (24.2)1.00 (Reference)
 >78.83–≤236.1751 (32.7)56 (35.7)1.67 (0.91–3.07)27 (32.5)1.73 (0.80–3.76)26 (39.4)1.90 (0.87–4.15)
 >236.1753 (34.0)61 (38.9)1.68 (0.93–3.04)36 (43.4)2.23 (1.07–4.67)24 (36.4)1.59 (0.73–3.47)0.75
Ptrend0.100.030.22
Arachidonic acid/P450 derived
5,6-DHET
 ≤268.1752 (33.3)44 (28.0)1.00 (Reference)18 (21.7)1.00 (Reference)26 (39.4)1.00 (Reference)
 >268.17–≤416.5051 (32.7)56 (35.7)1.33 (0.74–2.42)36 (43.3)2.48 (1.16–5.33)19 (28.8)0.73 (0.34–1.56)
 >416.5053 (34.0)57 (36.3)1.43 (0.79–2.62)29 (34.9)1.85 (0.84–4.08)21 (31.8)0.93 (0.44–1.94)0.05
Ptrend0.250.190.98
8,9-EET
 ≤526.6752 (33.3)54 (34.4)1.00 (Reference)23 (27.7)1.00 (Reference)28 (42.4)1.00 (Reference)
 >526.67–≤82051 (32.7)42 (26.8)0.77 (0.43–1.41)24 (28.9)1.08 (0.51–2.29)16 (24.2)0.63 (0.27–1.27)
 >82053 (34.0)61 (38.9)1.21 (0.67–2.17)36 (43.4)1.59 (0.77–3.27)22 (33.3)0.90 (0.43–1.87)0.11
Ptrend0.520.220.90
8,9-DHET
 ≤186.552 (33.3)42 (26.8)1.00 (Reference)20 (24.1)1.00 (Reference)20 (30.3)1.00 (Reference)
 >186.5–≤264.551 (33.3)61 (38.9)1.65 (0.91–3.00)34 (41.0)1.84 (0.86–3.91)26 (39.4)1.62 (0.77–3.42)
 >264.553 (34.0)54 (34.4)1.46 (0.80–2.68)29 (34.9)1.57 (0.72–3.40)20 (30.3)1.19 (0.55–2.59)0.32
Ptrend0.250.320.56
11,12-EET
 ≤401.6752 (33.3)47 (29.9)1.00 (Reference)25 (30.1)1.00 (Reference)19 (28.8)1.00 (Reference)
 >401.67–≤80551 (32.7)56 (35.7)1.20 (0.67–2.14)27 (32.5)1.09 (0.53–2.25)28 (42.4)1.49 (0.71–3.10)
 >80553 (34.0)54 (34.4)1.13 (0.62–2.04)31 (37.4)1.15 (0.56–2.35)19 (28.8)0.98 (0.45–2.15)0.61
Ptrend0.700.680.87
11,12-DHET
 ≤334.3352 (33.3)52 (33.1)1.00 (Reference)25 (30.1)1.00 (Reference)25 (37.9)1.00 (Reference)
 >334.33–≤441.6751 (32.7)52 (33.1)1.12 (0.63–2.01)29 (34.9)1.29 (0.63–2.65)22 (33.3)0.97 (0.47–2.01)
 >441.6753 (34.0)53 (33.8)1.16 (0.65–2.10)29 (34.9)1.35 (0.65–2.80)19 (28.8)0.82 (0.39–1.76)0.06
Ptrend0.610.550.74
14,15-EET
 ≤59052 (33.3)54 (34.4)1.00 (Reference)25 (30.1)1.00 (Reference)25 (37.9)1.00 (Reference)
 >590–≤1,76551 (32.7)43 (27.4)0.74 (0.41–1.34)23 (27.7)0.84 (0.39–1.77)19 (28.8)0.78 (0.37–1.66)
 >176553 (34.0)60 (38.2)1.01 (0.56–1.81)35 (42.2)1.13 (0.55–2.33)22 (33.3)0.85 (0.40–1.80)0.38
Ptrend0.990.740.71
14,15-DHET
 ≤448.3353 (34.0)52 (33.1)1.00 (Reference)24 (28.9)1.00 (Reference)25 (37.9)1.00 (Reference)
 >448.33–≤578.3350 (32.1)51 (32.5)1.01 (0.56–1.81)29 (34.9)1.03 (0.49–2.17)21 (31.8)0.98 (0.47–2.06)
 >578.3353 (34.0)54 (34.4)1.26 (0.70–2.27)30 (36.1)1.60 (0.77–3.35)20 (30.3)0.88 (0.41–1.88)0.05
Ptrend0.450.260.87
Arachidonic acid/nonenzymatic derived
11-HETE
 ≤136.5052 (33.3)52 (33.1)1.00 (Reference)27 (32.5)1.00 (Reference)24 (36.4)1.00 (Reference)
 >136.50–≤244.6751 (32.7)48 (30.6)1.11 (0.62–2.00)23 (27.7)1.06 (0.51–2.19)19 (28.8)0.94 (0.42–1.99)
 >244.6753 (34.0)57 (36.3)1.23 (0.69–2.20)33 (39.8)1.41 (0.69–2.89)23 (34.9)1.10 (0.52–2.30)0.85
Ptrend0.490.320.91
8-iso-PGFc
 0145 (92.9)147 (93.6)1.00 (Reference)76 (91.6)1.00 (Reference)63 (95.5)1.00 (Reference)
 >0 (detectable)11 (7.1)10 (6.4)0.81 (0.31–2.10)7 (8.4)1.40 (0.47–4.15)3 (4.6)0.34 (0.07–1.66)0.27
  • aORs and 95% CIs were estimated using unconditional logistic regression model adjusted for matching factors [age at blood collection (55–59, 60–64, 65–69, 70+ years), race (white, black, and other), study center, and time (a.m., p.m.) and date (3-month categories of blood collection)] and a priori selected risk factors (parity, duration of oral contraceptive use, duration of menopausal hormone therapy use, cigarette smoking, and BMI).

  • bStatistical test for heterogeneity across histologic subtypes was based on the Wald test.

  • cMetabolites with 90% or more individuals with nondetectable levels were categorized into detectable versus undetectable.

  • dTertile categories of the metabolites were based on the distribution among controls.

  • eP-values for trend across tertile as continuous variable were calculated using the Wald test.

  • fFDR q-values: 8-HETE = 0.17; 12,13-DHOME, 13-HODE, and 9,12,13-THOME = 0.06; and 9-HODE = 0.15.