Article Figures & Data
Tables
- Table 1.
Characteristics of ovarian cancer cases and controls in the NECC and the NHS
Characteristic NECC NHS* Cases Controls P† Cases Controls P† N 1,175 1,202 210 600 Mean (SD) Age (y)‡ 51 (13) 51 (13) 0.37 62 (8) 62 (8) 0.93 Parity among parous women 2.5 (1.3) 2.8 (1.5) <0.001 3.0 (1.3) 3.4 (1.5) 0.004 Duration oral contraceptive use (mo)§ 52 (54) 61 (55) 0.006 46 (42) 53 (49) 0.22 BMI (kg/m2) 26.3 (6.3) 25.7 (5.5) 0.02 25.7 (5.0) 25.7 (4.5) 0.94 Duration PMH use (mo)§ 78 (86) 74 (71) 0.64 96 (84) 85 (68) 0.18 Duration of lactation (mo)∥ 5.0 (10.0) 7.3 (13.2) <0.001 6.0 (10.3) 7.2 (9.7) 0.17 Percent of study population Parous 68 81 <0.001 89 93 0.05 Ever user of oral contraceptives 48 60 <0.001 42 45 0.57 History of tubal ligation 14 18 0.007 14 21 0.02 Ever user of PMH 17 20 0.14 71 63 0.02 Family history of ovarian cancer 5.1 2.8 0.004 9.1 3.7 0.002 Any history of genital talc use 29 24 0.003 40 39 0.79 Regular genital talc use (once a week or more) 27 20 <0.001 29 24 0.15 Daily genital talc use 16 12 0.006 18 13 0.08 Genotype frequencies, % GSTM1 null 51 53 0.42 48 52 0.36 GSTT1 null 21 22 0.85 19 21 0.45 NAT2 slow acetylator¶ 63 64 0.74 59 67 0.05 ↵* In the NHS, duration of lactation was collected in 1986, family history of ovarian cancer was first collected in 1992, and history of genital talc use was collected in 1982; for variables collected on multiple questionnaires, the value from two cycles (2-4 y) before the date of diagnosis for each case was used for the case and their matched controls.
↵† P values calculated using proc t test (continuous variables) or a χ2 test (binary variables).
↵‡ Cases and controls in each study population were matched (NHS) or frequency-matched (NECC) on age.
↵§ Duration of oral contraceptive use and PMH use among ever users.
↵∥ Total duration among parous women.
↵¶ NAT2 acetylation genotype based on analysis of three single nucleotide polymorphisms, I114T, R197Q, and G286E.
- Table 2.
Characteristics of participants in the NECC and the NHS by history of regular genital talc use (at least once a week)
Characteristic NECC NHS* No regular talc use Regular talc use P† No regular talc use Regular talc use P† Mean (SD) Age (y) 50 (13) 53 (12) <0.001 61 (8) 62 (8) 0.64 Parity among parous women 2.7 (1.4) 2.7 (1.4) 0.64 3.2 (1.4) 3.3 (1.5) 0.42 Age at first birth among parous women 25.0 (5.1) 24.6 (4.9) 0.22 25.0 (3.5) 24.4 (3.0) 0.03 Duration oral contraceptive use (mo)‡ 58 (55) 54 (54) 0.24 53 (49) 43 (42) 0.08 BMI (kg/m2) 25.7 (5.7) 27.0 (6.4) <0.001 25.6 (4.6) 26.2 (4.8) 0.13 Duration PMH use (mo)‡ 75 (74) 78 (86) 0.68 90 (74) 83 (70) 0.38 Duration of lactation (mo)§ 6.4 (12.1) 5.8 (11.5) 0.32 7.2 (10.2) 6.3 (9.6) 0.34 Physical activity (h/wk) 2.8 (5.0) 2.4 (3.8) 0.06 3.0 (2.3) 3.1 (2.4) 0.61 Percent of study population Parous 74 75 0.75 93 92 0.81 Ever user of oral contraceptives 55 50 0.03 44 44 0.96 History of tubal ligation 16 16 0.97 22 13 0.008 Postmenopause 45 54 <0.001 81 81 0.86 Ever user of PMH 17 26 <0.001 66 64 0.73 Ever smoker 53 55 0.35 57 47 0.02 Family history of ovarian cancer 3.9 4.1 0.82 4.5 6.4 0.31 Genotype frequencies, % GSTM1 null 52 52 0.72 51 49 0.66 GSTT1 null 21 22 0.59 22 17 0.15 NAT2 slow acetylator∥ 63 66 0.23 65 63 0.58 ↵* In the NHS, duration of lactation was collected in 1986, family history of ovarian cancer was first collected in 1992, and history of genital talc use was collected in 1982; for variables collected on multiple questionnaires, the value from two cycles (2-4 y) before the date of diagnosis for each case was used for the case and their matched controls.
↵† P values calculated using proc ttest (continuous variables) or a χ2 test (binary variables).
↵‡ Duration of oral contraceptive use and PMH use among ever users.
↵§ Total duration among parous women.
↵∥ NAT2 acetylation genotype based on analysis of three single nucleotide polymorphisms, I114T, R197Q, and G286E.
- Table 3.
RR (95% CI) for the association between genital talc use and ovarian cancer risk in the NECC and the NHS
NECC* NHS* Pooled† Cases (%) Controls (%) RR (95% CI) Cases (%) Controls (%) RR (95% CI) RR (95% CI) Total epithelial ovarian cancer: N‡ 1,175 1,202 210 600 Regular genital talc use (once a week or more) No 859 (73.2) 957 (79.7) 1.00 (reference) 138 (70.8) 414 (76.0) 1.00 (reference) 1.00 (reference) Yes 314 (26.8) 244 (20.3) 1.40 (1.15-1.70) 57 (29.2) 131 (24.0) 1.24 (0.83-1.83) 1.36 (1.14-1.63) Frequency of genital talc use Never 832 (70.9) 916 (76.3) 1.00 (reference) 120 (61.5) 352 (64.6) 1.00 (reference) 1.00 (reference) Less than once a week 27 (2.3) 41 (3.4) 0.72 (0.43-1.19) 18 (9.2) 62 (11.4) 0.98 (0.54-1.79) 0.82 (0.55-1.20) 1-6 times a week 123 (10.5) 96 (8.0) 1.33 (1.00-1.79) 22 (11.3) 61 (11.2) 1.01 (0.57-1.79) 1.26 (0.97-1.63) Daily 191 (16.3) 148 (12.3) 1.41 (1.10-1.79) 35 (18.0) 70 (12.8) 1.44 (0.88-2.37) 1.41 (1.14-1.76) Ptrend§ 0.002 0.18 <0.001 Serous invasive ovarian cancer: N‡ 450 1,202 93 263 Regular genital talc use (once a week or more) No 310 (69.0) 957 (79.7) 1.00 (reference) 60 (68.2) 177 (73.8) 1.00 (reference) 1.00 (reference) Yes 139 (31.0) 244 (20.3) 1.62 (1.26-2.09) 28 (31.8) 63 (26.3) 1.48 (0.82-2.68) 1.60 (1.26-2.02) Frequency of genital talc use Never 299 (66.6) 916 (76.3) 1.00 (reference) 54 (61.4) 151 (62.9) 1.00 (reference) 1.00 (reference) Less than once a week 11 (2.4) 41 (3.4) 0.65 (0.32-1.33) 6 (6.8) 26 (10.8) 0.79 (0.29-2.11) 0.70 (0.39-1.24) 1-6 times a week 56 (12.5) 96 (8.0) 1.56 (1.08-2.26) 12 (13.6) 25 (10.4) 1.64 (0.71-3.79) 1.58 (1.12-2.21) Daily 83 (18.5) 148 (12.3) 1.61 (1.18-2.20) 16 (18.2) 38 (15.8) 1.34 (0.65-2.76) 1.56 (1.17-2.08) Ptrend§ <0.001 0.29 <0.001 ↵* Unconditional (NECC) and conditional (NHS) logistic regression adjusted for age, study center (NECC only), duration of oral contraceptive use (months), parity (continuous), tubal ligation, BMI (kg/m2, continuous), and duration of PMH use (months).
↵† P values for tests for heterogeneity comparing the NECC and NHS results were all >0.38.
↵‡ Frequencies do not add up to total N due to missing data on talc use.
↵§ Weighted by the midpoint of each category of genital talc use frequency and calculated using the Wald test.
- Table 4.
RR (95% CI) for the association between GSTM1, GSTT1, and NAT2 genotype and epithelial ovarian cancer risk in the NECC and the NHS
NECC* NHS* Pooled† Cases (%) Controls (%) RR (95% CI) Cases (%) Controls (%) RR (95% CI) RR (95% CI) N‡ 1,175 1,202 210 600 GSTM1 genotype Present 573 (49.1) 567 (47.4) 1.00 (reference) 102 (52.3) 268 (48.5) 1.00 (reference) 1.00 (reference) Null 594 (50.9) 628 (52.6) 0.93 (0.79-1.10) 93 (47.7) 285 (51.5) 0.83 (0.58-1.17) 0.91 (0.78-1.06) GSTT1 genotype Present 919 (78.8) 938 (78.5) 1.00 (reference) 157 (81.3) 439 (78.8) 1.00 (reference) 1.00 (reference) Null 247 (21.2) 257 (21.5) 0.98 (0.80-1.21) 36 (18.7) 118 (21.2) 0.87 (0.57-1.33) 0.96 (0.80-1.16) NAT2 genotype Rapid/intermediate acetylator 387 (36.8) 405 (36.1) 1.00 (reference) 77 (41.0) 182 (33.0) 1.00 (reference) 1.00 (reference) Slow acetylator 665 (63.2) 717 (63.9) 0.97 (0.81-1.15) 111 (59.0) 369 (67.0) 0.65 (0.45-0.95) 0.82 (0.57-1.20) Combined GSTM1/GSTT1 genotype Both present 445 (38.2) 430 (36.0) 1.00 (reference) 81 (44.3) 206 (39.2) 1.00 (reference) 1.00 (reference) M1 null, T1 present 474 (40.7) 508 (42.5) 0.91 (0.76-1.10) 68 (37.2) 208 (39.5) 0.82 (0.54-1.22) 0.89 (0.75-1.06) M1 present, T1 null 128 (11.0) 137 (11.5) 0.94 (0.71-1.24) 17 (9.3) 49 (9.3) 0.98 (0.52-1.84) 0.94 (0.73-1.22) Both null 119 (10.2) 120 (10.0) 0.94 (0.70-1.26) 17 (9.3) 63 (12.0) 0.65 (0.34-1.24) 0.88 (0.67-1.15) Combined GSTM1/NAT2 genotype GSTM1 present, NAT2 rapid 195 (18.6) 188 (16.9) 1.00 (reference) 37 (21.0) 85 (16.4) 1.00 (reference) 1.00 (reference) GSTM1 null, NAT2 rapid 189 (18.1) 214 (19.2) 0.82 (0.61-1.09) 35 (19.9) 91 (17.5) 0.96 (0.53-1.74) 0.84 (0.65-1.09) GSTM1 present, NAT2 slow 315 (30.1) 343 (30.7) 0.86 (0.66-1.11) 56 (31.8) 161 (31.0) 0.87 (0.51-1.50) 0.86 (0.68-1.09) GSTM1 null, NAT2 slow 347 (33.2) 371 (33.2) 0.88 (0.68-1.14) 48 (27.3) 183 (35.2) 0.57 (0.33-0.98) 0.76 (0.50-1.14) Combined GSTT1/NAT2 genotype GSTT1 present, NAT2 rapid 296 (28.3) 312 (28.0) 1.00 (reference) 52 (29.7) 144 (27.5) 1.00 (reference) 1.00 (reference) GSTT1 null, NAT2 rapid 88 (8.4) 90 (8.1) 1.03 (0.73-1.45) 17 (9.7) 30 (5.7) 1.55 (0.76-3.16) 1.11 (0.81-1.52) GSTT1 present, NAT2 slow 519 (49.7) 562 (50.4) 0.97 (0.79-1.19) 90 (51.4) 270 (51.6) 0.87 (0.57-1.33) 0.95 (0.79-1.14) GSTT1 null, NAT2 slow 142 (13.6) 152 (13.6) 0.98 (0.74-1.31) 16 (9.1) 79 (15.1) 0.51 (0.26-0.99) 0.76 (0.40-1.43) ↵* Unconditional (NECC) and conditional (NHS) logistic regression adjusted for age, study center (NECC only), duration of oral contraceptive use (months), parity (continuous), tubal ligation, BMI (kg/m2, continuous), and duration of PMH use (months).
↵† P values for tests for heterogeneity comparing the NECC and NHS results were all >0.06.
↵‡ Frequencies do not add up to total N due to missing genotype data.
- Table 5.
Pooled RR (95% CI) for the association between regular talc use and ovarian cancer risk, stratified by genotype, in the NECC and the NHS
All cancers Serous invasive cancers Cases and controls in pooled analysis All cases Serous invasive Controls Regular talc use Regular talc use Regular talc Regular talc Regular talc No Yes No Yes No Yes No Yes No Yes Gene/stratum GSTM1 genotype Present (+) 1.0 (reference) 1.6 (1.2-2.0) 1.0 (reference) 2.0 (1.4-2.8) 480 189 173 90 646 165 Null (-) 1.0 (reference) 1.3 (1.0-1.6) 1.0 (reference) 1.4 (1.0-1.9) 498 179 190 76 690 198 Pinteraction* 0.13 0.08 GSTT1 genotype Present (+) 1.0 (reference) 1.2 (1.0-1.5) 1.0 (reference) 1.5 (1.2-2.0) 785 278 288 129 1,035 301 Null (-) 1.0 (reference) 2.1 (1.4-3.2) 1.0 (reference) 2.4 (1.4-4.0) 194 87 71 38 300 67 Pinteraction* 0.03 0.18 NAT2 genotype Rapid/intermediate acetylator 1.0 (reference) 1.5 (1.1-2.0) 1.0 (reference) 1.9 (1.2-2.8) 330 128 123 57 459 113 Slow acetylator 1.0 (reference) 1.4 (1.1-1.8) 1.0 (reference) 1.6 (1.2-2.1) 552 217 204 96 819 233 Pinteraction* 0.60 0.58 GSTM1/GSTT1 genotype† GSTM1+, GSTT1+ 1.0 (reference) 1.4 (1.0-1.8) 1.0 (reference) 1.7 (1.2-2.5) 378 142 136 68 479 140 GSTM1-, GSTT1+ 1.0 (reference) 1.2 (0.9-1.5) 1.0 (reference) 1.4 (0.9-1.9) 400 135 151 60 541 154 GSTM1+, GSTT1- 1.0 (reference) 2.8 (1.6-5.0) 1.0 (reference) 4.8 (2.1-11) 98 47 34 22 158 24 GSTM1-, GSTT1- 1.0 (reference) 1.6 (0.9-2.9) 1.0 (reference) 1.4 (0.6-3.1) 94 40 36 16 138 41 Pinteraction* 0.03 0.09 NOTE: NECC: unconditional logistic regression adjusted for age, study center, duration of oral contraceptive use (months), parity (continuous), tubal ligation, BMI (kg/m2, continuous), and duration of PMH use (months); NHS: unconditional logistic regression adjusted for age (months), menopausal status at diagnosis (post, pre/dubious), DNA source, duration of oral contraceptive use (months), parity (continuous), tubal ligation, BMI (kg/m2, continuous), and duration of PMH use (months). P values for tests for heterogeneity comparing the NECC and NHS results were all >0.36.
↵* P values for interaction based on likelihood ratio test comparing unconditional logistic regression models with and without gene-talc interaction terms.
↵† NHS analysis adjusted for age, menopausal status at diagnosis, and DNA source only to improve stability of estimates.
Additional Files
Supplementary Data, Gates, et al.
Files in this Data Supplement: