Introduction
Subjects and methods
Study cohort, cases and follow-up
Acrylamide intake assessment
Selection of genes and SNPs
DNA isolation and genotyping
Statistical analysis
Results
Variable | Ovarian cancer cases | Subcohort |
---|---|---|
na
| 364 | 1474 |
Dietary variables
| ||
Acrylamide intake (μg/day) | 21.9 (13.1) | 20.9 (11.8) |
Total energy intake (kcal) | 1684 (400) | 1689 (399) |
Non-dietary variables
| ||
Age (yrs) | 61.4 (4.3) | 61.4 (4.3) |
Body mass index (kg/m2) | 25.0 (3.6) | 25.1 (3.6) |
Age at menarche (yrs) | 13.7 (1.8) | 13.7 (1.8) |
Age at menopause (yrs) | 49.0 (4.1) | 48.8 (4.4) |
Parity, n children | 2.4 (2.2) | 2.8 (2.2) |
n cigarettes per day | 3.5 (6.9) | 4.5 (7.7) |
n smoking years | 9.1 (14.5) | 11.3 (15.7) |
Cigarette smoking status % | ||
Never smokers | 64.8 | 58.7 |
Former smokers | 19.6 | 20.9 |
Current smokers | 15.6 | 20.4 |
Ever use of postmenopausal hormone treatment, % yes | 12.1 | 13.3 |
Ever use of oral contraceptives, % yes | 16.4 | 25.4 |
Main effect of acrylamide
n cases | Per 10 µg/day increment | Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 |
p trend | |
---|---|---|---|---|---|---|---|---|
HR (95% CI)a
| HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | |||
All women | 373 | 1.06 (0.98–1.16) | Ref (1.00) | 1.07 (0.73–1.54) | 1.10 (0.75–1.61) | 1.05 (0.71–1.53) | 1.38 (0.95–1.99) | 0.13 |
Never-smoking women | 243 | 1.15 (1.02–1.30) | Ref (1.00) | 1.37 (0.85–2.21) | 1.61 (0.98–2.65) | 1.50 (0.92–2.44) | 1.85 (1.15–2.95) | 0.01 |
Main effect of the SNPs
Main effects SNPs | Homozygous wildtype | 1 or 2 variant alleles | 1 variant allele | 2 variant alleles |
p trend per allele | Benjamini–Hochberg-adjusted p value | ||||
---|---|---|---|---|---|---|---|---|---|---|
N cases | HR (95% CI)a
| N cases | HR (95% CI)a
| N cases | HR (95% CI)a
| N cases | HR (95% CI)a
| |||
CAT, rs511895 | 86 | Ref | 215 | 1.25 (0.95–1.63) | 154 | 1.17 (0.88–1.56) | 61 | 1.48 (1.04–2.13) | 0.04 | 0.59 |
CYP1A1, rs4646903 | 261 | Ref | 36 | 0.70 (0.48–1.02) | 36 | 0.70 (0.48–1.02) | na | 0.06 | 0.59 | |
CYP1B1, rs1056827 | 144 | Ref | 154 | 1.26 (0.99–1.62) | 127 | 1.24 (0.96–1.61) | 27 | 1.36 (0.87–2.14) | 0.06 | 0.59 |
MUTYH, rs3219489 | 189 | Ref | 112 | 0.78 (0.60–1.00) | 97 | 0.79 (0.61–1.03) | 15 | 0.70 (0.40–1.23) | 0.05 | 0.59 |
TXN, rs2301241 | 95 | Ref | 206 | 1.26 (0.97–1.65) | 147 | 1.18 (0.89–1.56) | 59 | 1.55 (1.08–2.22) | 0.02 | 0.59 |
GSTM1 deletion | 1 or 2 alleles present | Homozygous deletion |
p value | Benjamini–Hochberg-adjusted p value | ||
---|---|---|---|---|---|---|
N cases | HR (95% CI)a
| N cases | HR (95% CI)a
| |||
Deletion represented by | ||||||
Both GSTM1 SNPs | 226 | Ref | 75 | 0.74 (0.56–0.98) | 0.03 | 0.59 |
rs10857795 | 214 | Ref | 87 | 0.73 (0.56–0.95) | 0.02 | 0.59 |
rs200184852 | 185 | Ref | 116 | 0.84 (0.66–1.09) | 0.19 | 0.59 |
Interaction between acrylamide and SNPs
SNPa
| Acrylamide, continuous intake | Acrylamide, tertiles of intake | Interaction | |||||||
---|---|---|---|---|---|---|---|---|---|---|
10 µg/day | Tertile 1 | Tertile 2 | Tertile 3 |
p for trend |
p for linear interaction | |||||
N cases | HR (95% CI)c
| N cases | HR (95% CI)c
| N cases | HR (95% CI)c
| Raw p | Benjamini–Hochberg adjusted p value | |||
All | ||||||||||
CYP2E1, rs915906 = 0b
| 1.12 (0.99–1.26) | 55 | Ref (1.00) | 50 | 0.98 (0.64–1.50) | 78 | 1.35 (0.91–2.01) | 0.12 | 0.52 | 0.81 |
CYP2E1, rs915906 = 1b
| 1.00 (0.76–1.32) | 33 | Ref (1.00) | 14 | 0.42 (0.20–0.87) | 22 | 0.65 (0.33–1.27) | 0.21 | ||
Never-smokers | ||||||||||
CYP2E1, rs915906 = 0 | 1.18 (1.01–1.38) | 32 | Ref (1.00) | 38 | 1.36 (0.80–2.32) | 49 | 1.57 (0.95–2.59) | 0.08 | 0.92 | 0.96 |
CYP2E1, rs915906 = 1 | 1.09 (0.77–1.53) | 20 | Ref (1.00) | 9 | 0.45 (0.17–1.19) | 15 | 0.72 (0.30–1.72) | 0.47 | ||
All | ||||||||||
CYP2E1, rs2480258 = 0 | 1.13 (0.99–1.28) | 51 | Ref (1.00) | 47 | 1.03 (0.66–1.62) | 73 | 1.40 (0.93–2.13) | 0.10 | 0.45 | 0.78 |
CYP2E1, rs2480258 = 1 | 0.98 (0.79–1.22) | 37 | Ref (1.00) | 17 | 0.43 (0.22–0.84) | 27 | 0.66 (0.37–1.20) | 0.18 | ||
Never-smokers | ||||||||||
CYP2E1, rs2480258 = 0 | 1.19 (1.02–1.40) | 30 | Ref (1.00) | 36 | 1.52 (0.87–2.64) | 47 | 1.75 (1.04–2.97) | 0.04 | 0.87 | 0.96 |
CYP2E1, rs2480258 = 1 | 1.07 (0.78–1.48) | 22 | Ref (1.00) | 11 | 0.43 (0.18–1.02) | 17 | 0.59 (0.26–1.34) | 0.24 | ||
All | ||||||||||
CYP2E1, rs6413432 = 0 | 1.07 (0.96–1.19) | 71 | Ref (1.00) | 60 | 0.94 (0.66–1.34) | 85 | 1.09 (0.79–1.52) | 0.58 | 0.88 | 0.93 |
CYP2E1, rs6413432 = 1 | 1.04 (0.74–1.47) | 17 | Ref (1.00) | 4 | 0.19 (0.06–0.57) | 15 | 0.76 (0.29–1.97) | 0.49 | ||
Never-smokers | ||||||||||
CYP2E1, rs6413432 = 0 | 1.09 (0.94–1.25) | 46 | Ref (1.00) | 44 | 1.07 (0.70–1.65) | 54 | 1.05 (0.69–1.58) | 0.83 | 0.19 | 0.65 |
CYP2E1, rs6413432 = 1 | 1.49 (0.89–2.49) | 6 | Ref (1.00) | 3 | 0.20 (0.04–1.06) | 10 | 0.92 (0.24–3.49) | 0.98 | ||
All | ||||||||||
GSTM1 present, all SNPs | 1.07 (0.94–1.22) | 65 | Ref (1.00) | 48 | 0.79 (0.51–1.21) | 76 | 1.09 (0.73–1.61) | 0.62 | 0.73 | 0.90 |
GSTM1 deleted, all SNPs | 1.15 (0.90–1.47) | 23 | Ref (1.00) | 16 | 0.65 (0.31–1.35) | 24 | 1.02 (0.50–2.08) | 0.92 | ||
Never-smokers | ||||||||||
GSTM1 present, all SNPs | 1.13 (0.96–1.32) | 40 | Ref (1.00) | 34 | 1.04 (0.60–1.79) | 47 | 1.25 (0.76–2.05) | 0.37 | 0.43 | 0.76 |
GSTM1 deleted, all SNPs | 1.29 (0.89–1.86) | 12 | Ref (1.00) | 13 | 1.07 (0.43–2.62) | 17 | 1.25 (0.51–3.03) | 0.62 | ||
All | ||||||||||
GSTT1 present, rs4630 | 1.15 (1.03–1.29) | 68 | Ref (1.00) | 52 | 0.83 (0.56–1.25) | 89 | 1.36 (0.94–1.97) | 0.09 | 0.11 | 0.67 |
GSTT1 deleted, rs4630 | 0.79 (0.53–1.19) | 20 | Ref (1.00) | 12 | 0.50 (0.20–1.24) | 11 | 0.31 (0.12–0.77) | 0.01 | ||
Never-smokers | ||||||||||
GSTT1 present, rs4630 | 1.23 (1.06–1.44) | 40 | Ref (1.00) | 41 | 1.14 (0.69–1.87) | 57 | 1.59 (0.99–2.54) | 0.05 | 0.26 | 0.65 |
GSTT1 deleted, rs4630 | 0.87 (0.53–1.44) | 12 | Ref (1.00) | 6 | 0.52 (0.15–1.81) | 7 | 0.34 (0.10–1.22) | 0.10 | ||
All | ||||||||||
GSTP1, rs1695 = 0 | 1.05 (0.88–1.25) | 31 | Ref (1.00) | 32 | 0.96 (0.58–1.58) | 38 | 0.99 (0.59–1.66) | 0.98 | 0.81 | 0.90 |
GSTP1, rs1695 = 1 | 1.07 (0.94–1.23) | 57 | Ref (1.00) | 32 | 0.63 (0.41–0.97) | 62 | 1.02 (0.70–1.50) | 0.90 | ||
Never-smokers | ||||||||||
GSTP1, rs1695 = 0 | 1.07 (0.85–1.36) | 19 | Ref (1.00) | 25 | 1.17 (0.65–2.11) | 24 | 0.91 (0.48–1.70) | 0.74 | 0.79 | 0.96 |
GSTP1, rs1695 = 1 | 1.13 (0.95–1.34) | 33 | Ref (1.00) | 22 | 0.73 (0.42–1.26) | 40 | 1.09 (0.66–1.79) | 0.74 | ||
All | ||||||||||
GSTA5, rs4715354 = 0 | 0.98 (0.80–1.20) | 24 | Ref (1.00) | 20 | 1.20 (0.56–2.54) | 25 | 1.06 (0.53–2.13) | 0.87 | 0.56 | 0.81 |
GSTA5, rs4715354 = 1 | 1.13 (0.99–1.28) | 64 | Ref (1.00) | 44 | 0.71 (0.46–1.08) | 75 | 1.15 (0.78–1.69) | 0.43 | ||
Never-smokers | ||||||||||
GSTA5, rs4715354 = 0 | 1.03 (0.80–1.32) | 14 | Ref (1.00) | 13 | 1.48 (0.55–3.94) | 19 | 1.33 (0.56–3.13) | 0.55 | 0.61 | 0.83 |
GSTA5, rs4715354 = 1 | 1.21 (1.00–1.46) | 38 | Ref (1.00) | 34 | 0.97 (0.58–1.65) | 45 | 1.25 (0.75–2.07) | 0.38 | ||
All | ||||||||||
EPHX1, rs1051740 = 0 | 1.06 (0.89–1.27) | 46 | Ref (1.00) | 26 | 0.55 (0.34–0.89) | 47 | 0.86 (0.55–1.35) | 0.55 | 0.87 | 0.93 |
EPHX1, rs1051740 = 1 | 1.07 (0.94–1.22) | 42 | Ref (1.00) | 38 | 0.98 (0.62–1.53) | 53 | 1.19 (0.78–1.81) | 0.41 | ||
Never-smokers | ||||||||||
EPHX1, rs1051740 = 0 | 1.10 (0.88–1.38) | 31 | Ref (1.00) | 20 | 0.63 (0.36–1.12) | 31 | 0.79 (0.46–1.37) | 0.41 | 0.88 | 0.96 |
EPHX1, rs1051740 = 1 | 1.12 (0.94–1.33) | 21 | Ref (1.00) | 27 | 1.32 (0.74–2.36) | 33 | 1.36 (0.77–2.40) | 0.30 |