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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Articles

Talc Use, Variants of the GSTM1, GSTT1, and NAT2 Genes, and Risk of Epithelial Ovarian Cancer

Margaret A. Gates, Shelley S. Tworoger, Kathryn L. Terry, Linda Titus-Ernstoff, Bernard Rosner, Immaculata De Vivo, Daniel W. Cramer and Susan E. Hankinson
Margaret A. Gates
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Shelley S. Tworoger
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Kathryn L. Terry
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Linda Titus-Ernstoff
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Bernard Rosner
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Immaculata De Vivo
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Daniel W. Cramer
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Susan E. Hankinson
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DOI: 10.1158/1055-9965.EPI-08-0399 Published September 2008
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  • Table 1.

    Characteristics of ovarian cancer cases and controls in the NECC and the NHS

    CharacteristicNECC
    NHS*
    CasesControlsP†CasesControlsP†
    N1,1751,202210600
    Mean (SD)
        Age (y)‡51 (13)51 (13)0.3762 (8)62 (8)0.93
        Parity among parous women2.5 (1.3)2.8 (1.5)<0.0013.0 (1.3)3.4 (1.5)0.004
        Duration oral contraceptive use (mo)§52 (54)61 (55)0.00646 (42)53 (49)0.22
        BMI (kg/m2)26.3 (6.3)25.7 (5.5)0.0225.7 (5.0)25.7 (4.5)0.94
        Duration PMH use (mo)§78 (86)74 (71)0.6496 (84)85 (68)0.18
        Duration of lactation (mo)∥5.0 (10.0)7.3 (13.2)<0.0016.0 (10.3)7.2 (9.7)0.17
    Percent of study population
        Parous6881<0.00189930.05
        Ever user of oral contraceptives4860<0.00142450.57
        History of tubal ligation14180.00714210.02
        Ever user of PMH17200.1471630.02
        Family history of ovarian cancer5.12.80.0049.13.70.002
        Any history of genital talc use29240.00340390.79
        Regular genital talc use (once a week or more)2720<0.00129240.15
        Daily genital talc use16120.00618130.08
    Genotype frequencies, %
        GSTM1 null51530.4248520.36
        GSTT1 null21220.8519210.45
        NAT2 slow acetylator¶63640.7459670.05
    • ↵* 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)

    CharacteristicNECC
    NHS*
    No regular talc useRegular talc useP†No regular talc useRegular talc useP†
    Mean (SD)
        Age (y)50 (13)53 (12)<0.00161 (8)62 (8)0.64
        Parity among parous women2.7 (1.4)2.7 (1.4)0.643.2 (1.4)3.3 (1.5)0.42
        Age at first birth among parous women25.0 (5.1)24.6 (4.9)0.2225.0 (3.5)24.4 (3.0)0.03
        Duration oral contraceptive use (mo)‡58 (55)54 (54)0.2453 (49)43 (42)0.08
        BMI (kg/m2)25.7 (5.7)27.0 (6.4)<0.00125.6 (4.6)26.2 (4.8)0.13
        Duration PMH use (mo)‡75 (74)78 (86)0.6890 (74)83 (70)0.38
        Duration of lactation (mo)§6.4 (12.1)5.8 (11.5)0.327.2 (10.2)6.3 (9.6)0.34
        Physical activity (h/wk)2.8 (5.0)2.4 (3.8)0.063.0 (2.3)3.1 (2.4)0.61
    Percent of study population
        Parous74750.7593920.81
        Ever user of oral contraceptives55500.0344440.96
        History of tubal ligation16160.9722130.008
        Postmenopause4554<0.00181810.86
        Ever user of PMH1726<0.00166640.73
        Ever smoker53550.3557470.02
        Family history of ovarian cancer3.94.10.824.56.40.31
    Genotype frequencies, %
        GSTM1 null52520.7251490.66
        GSTT1 null21220.5922170.15
        NAT2 slow acetylator∥63660.2365630.58
    • ↵* 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‡1,1751,202210600
    Regular genital talc use (once a week or more)
        No859 (73.2)957 (79.7)1.00 (reference)138 (70.8)414 (76.0)1.00 (reference)1.00 (reference)
        Yes314 (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
        Never832 (70.9)916 (76.3)1.00 (reference)120 (61.5)352 (64.6)1.00 (reference)1.00 (reference)
        Less than once a week27 (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 week123 (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)
        Daily191 (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§0.0020.18<0.001
    Serous invasive ovarian cancer:
    N‡4501,20293263
    Regular genital talc use (once a week or more)
        No310 (69.0)957 (79.7)1.00 (reference)60 (68.2)177 (73.8)1.00 (reference)1.00 (reference)
        Yes139 (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
        Never299 (66.6)916 (76.3)1.00 (reference)54 (61.4)151 (62.9)1.00 (reference)1.00 (reference)
        Less than once a week11 (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 week56 (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)
        Daily83 (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§<0.0010.29<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‡1,1751,202210600
    GSTM1 genotype
        Present573 (49.1)567 (47.4)1.00 (reference)102 (52.3)268 (48.5)1.00 (reference)1.00 (reference)
        Null594 (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
        Present919 (78.8)938 (78.5)1.00 (reference)157 (81.3)439 (78.8)1.00 (reference)1.00 (reference)
        Null247 (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 acetylator387 (36.8)405 (36.1)1.00 (reference)77 (41.0)182 (33.0)1.00 (reference)1.00 (reference)
        Slow acetylator665 (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 present445 (38.2)430 (36.0)1.00 (reference)81 (44.3)206 (39.2)1.00 (reference)1.00 (reference)
        M1 null, T1 present474 (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 null128 (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 null119 (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 rapid195 (18.6)188 (16.9)1.00 (reference)37 (21.0)85 (16.4)1.00 (reference)1.00 (reference)
        GSTM1 null, NAT2 rapid189 (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 slow315 (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 slow347 (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 rapid296 (28.3)312 (28.0)1.00 (reference)52 (29.7)144 (27.5)1.00 (reference)1.00 (reference)
        GSTT1 null, NAT2 rapid88 (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 slow519 (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 slow142 (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
    NoYesNoYesNoYesNoYesNoYes
    Gene/stratum
    GSTM1 genotype
        Present (+)1.0 (reference)1.6 (1.2-2.0)1.0 (reference)2.0 (1.4-2.8)48018917390646165
        Null (-)1.0 (reference)1.3 (1.0-1.6)1.0 (reference)1.4 (1.0-1.9)49817919076690198
        Pinteraction*0.130.08
    GSTT1 genotype
        Present (+)1.0 (reference)1.2 (1.0-1.5)1.0 (reference)1.5 (1.2-2.0)7852782881291,035301
        Null (-)1.0 (reference)2.1 (1.4-3.2)1.0 (reference)2.4 (1.4-4.0)19487713830067
        Pinteraction*0.030.18
    NAT2 genotype
        Rapid/intermediate acetylator1.0 (reference)1.5 (1.1-2.0)1.0 (reference)1.9 (1.2-2.8)33012812357459113
        Slow acetylator1.0 (reference)1.4 (1.1-1.8)1.0 (reference)1.6 (1.2-2.1)55221720496819233
        Pinteraction*0.600.58
    GSTM1/GSTT1 genotype†
        GSTM1+, GSTT1+1.0 (reference)1.4 (1.0-1.8)1.0 (reference)1.7 (1.2-2.5)37814213668479140
        GSTM1-, GSTT1+1.0 (reference)1.2 (0.9-1.5)1.0 (reference)1.4 (0.9-1.9)40013515160541154
        GSTM1+, GSTT1-1.0 (reference)2.8 (1.6-5.0)1.0 (reference)4.8 (2.1-11)9847342215824
        GSTM1-, GSTT1-1.0 (reference)1.6 (0.9-2.9)1.0 (reference)1.4 (0.6-3.1)9440361613841
        Pinteraction*0.030.09
    • 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

  • Tables
  • Supplementary Data, Gates, et al.

    Files in this Data Supplement:

    • Supplementary Table 1
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Cancer Epidemiology Biomarkers & Prevention: 17 (9)
September 2008
Volume 17, Issue 9
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Talc Use, Variants of the GSTM1, GSTT1, and NAT2 Genes, and Risk of Epithelial Ovarian Cancer
Margaret A. Gates, Shelley S. Tworoger, Kathryn L. Terry, Linda Titus-Ernstoff, Bernard Rosner, Immaculata De Vivo, Daniel W. Cramer and Susan E. Hankinson
Cancer Epidemiol Biomarkers Prev September 1 2008 (17) (9) 2436-2444; DOI: 10.1158/1055-9965.EPI-08-0399

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Talc Use, Variants of the GSTM1, GSTT1, and NAT2 Genes, and Risk of Epithelial Ovarian Cancer
Margaret A. Gates, Shelley S. Tworoger, Kathryn L. Terry, Linda Titus-Ernstoff, Bernard Rosner, Immaculata De Vivo, Daniel W. Cramer and Susan E. Hankinson
Cancer Epidemiol Biomarkers Prev September 1 2008 (17) (9) 2436-2444; DOI: 10.1158/1055-9965.EPI-08-0399
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