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Epidemiology and Prevention

Candidate Genetic Modifiers of Individual Susceptibility to Renal Cell Carcinoma

A Study of Polymorphic Human Xenobiotic-metabolizing Enzymes

Sandrine Longuemaux, Claudine Deloménie, Catherine Gallou, Arnaud Méjean, Monique Vincent-Viry, Raymonde Bouvier, Dominique Droz, Rajagopal Krishnamoorthy, Marie-Madeleine Galteau, Claudine Junien, Christophe Béroud and Jean-Marie Dupret
Sandrine Longuemaux
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Claudine Deloménie
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Catherine Gallou
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Arnaud Méjean
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Monique Vincent-Viry
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Raymonde Bouvier
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Dominique Droz
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Rajagopal Krishnamoorthy
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Marie-Madeleine Galteau
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Claudine Junien
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Christophe Béroud
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Jean-Marie Dupret
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DOI:  Published June 1999
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    Fig. 1.

    Association of RCC susceptibility with single and combined genotypes. GSTM1 (−) and GSTT1 (−), genotypes with two null alleles; GSTM1 (+) and GSTT1 (+), one or two active alleles; GSTM1 (A), genotype with at least one GSTM1*A allele; GSTM1 (non A), genotype with no GSTM1*A allele; CYP2D6 (−), NAT2 (−) and NQO1 (−), two alleles each associated with low levels or a complete lack of enzyme activity; CYP2D6 (+), NAT2 (+), and NQO1 (+), one or two alleles associated with rapid or normal enzyme activity; CYP1A1 (m) and GSTP1 (m), one or two alleles that may affect enzyme activity; CYP1A1 (+) and GSTP1 (+), two alleles possibly associated with normal enzyme activity. The OR and 95% CIs were calculated by logistic regression analysis, with adjustment for age and gender. An OR >1 corresponds to an increase in presumed risk, and an OR <1 corresponds to a decrease in the risk.

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  • Table 1

    Allele frequencies in RCC cases and controlsa

    EnzymeAllele or genotypeFrequency (%)
    ControlsReferencesbCases
    CYP1A1cCYP1A1*1 (wt)86.289.381.9
    CYP1A1*2A 5.55.08.2
    CYP1A1*2B 2.82.73.5
    CYP1A1*3 0.00.00.0
    CYP1A1*4 5.53.06.4
    CYP2D6CYP2D6 (wt)d73.072.571.2
    CYP2D6*3 1.41.81.2
    CYP2D6*4 19.720.418.9
    CYP2D6*5 2.62.54.6
    CYP2D6*6 1.911.2
    CYP2D6*8 0.0<0.10.0
    CYP2D6*10 1.41.72.9
    CYP2D6*12 0.0<0.10.0
    CYP2D6*14 0.00.00.0
    NQO1NQO1*1 (wt)80.581.376.3
    NQO1*2 19.518.723.7
    GSTM1 GSTM1*0/*0 55.553.351.4
    GSTM1*A/*A and GSTM1*A/*022.730.329.5
    GSTM1*B/*B and GSTM1*B/*017.513.013.9
    GSTM1*A/*B 4.33.45.2
    GSTT1GSTT1 wt/wt and GSTT1 wt/*081.080.585.6
    GSTT1*0/*0 19.019.514.4
    GSTP1GSTP1*A (wt)69.070.365.3
    GSTP1*B 31.029.734.7
    GSTP1*C 0.0−e0.0
    NAT2NAT2*4 (wt)25.324.323.3
    NAT2*5 45.346.548.1
    NAT2*6 28.027.326.4
    NAT2*7 1.21.81.9
    NAT2*14 0.2<0.10.3
    • a The frequencies obtained are for: 210–211 controls and 171–173 RCC cases for CYP1A1, CYP2D6, NQO1, GSTM1, and GSTT1; 211 controls and 159 RCC patients for NAT2; and 189 controls and 160 RCC patients for GSTP1.

    • b Reference data are taken from studies with European Caucasians, restricted to those with similar distributions of age and sex, as the control subjects: 880 individuals (42) for CYP1A1; 784 individuals (33 , 43) for CYP2D6; 235 individuals (20 , 44) for NQO1; 950 individuals (18 , 45) for GSTM1; 867 individuals (18 , 45) for GSTT1; 180 individuals (46) for GSTP1; and 1128 individuals (18 , 47 48 49) for NAT2.

    • c Nomenclature of alleles is as described by Cascorbi et al. (42) .

    • d CYP2D6 (wt) represents the alleles associated with normal or ultrarapid CYP2D6 activity; the CYP2D6*10 allele has also been excluded from the PM alleles (33 , 50) .

    • e No data have been reported with regards to GSTP1*C allele frequency in Caucasians.

  • Table 2

    Distribution of genotypes in RCC and control populations

    Locuswt/wt (%)wt/ma (%)m/m (%)Number of subjects
    CYP1A1 Controls156 (74.3)50 (23.8)4 (1.9)210
    Cases114 (66.7)52 (30.4)5 (2.9)171
    CYP2D6 Controls110 (52.1)89 (42.2)12 (5.7)211
    Cases93 (54.1)65 (37.8)14 (8.1)172
    NQO1 Controls136 (64.8)66 (31.4)8 (3.8)210
    Cases102 (58.9)60 (34.7)11 (6.4)173
    GSTP1 Controls93 (49.2)75 (39.7)21 (11.1)189
    Cases71 (44.4)67 (41.9)22 (13.7)160
    NAT2 Controls16 (7.6)75 (35.5)120 (56.9)211
    Cases10 (6.3)54 (34.0)95 (59.7)159
    • a m, allele carrying at least one nucleotide change associated with altered phenotypic activity (variant CYP1A1* alleles; PM CYP2D6* alleles, defective NQO1* alleles; variant GSTP1* alleles, and slow acetylator NAT2* alleles). wt, allele with no such nucleotide changes. For distribution of GSTM1 and GSTT1 genotypes, see Table 1 <$REFLINK> .

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June 1999
Volume 59, Issue 12
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Candidate Genetic Modifiers of Individual Susceptibility to Renal Cell Carcinoma
Sandrine Longuemaux, Claudine Deloménie, Catherine Gallou, Arnaud Méjean, Monique Vincent-Viry, Raymonde Bouvier, Dominique Droz, Rajagopal Krishnamoorthy, Marie-Madeleine Galteau, Claudine Junien, Christophe Béroud and Jean-Marie Dupret
Cancer Res June 15 1999 (59) (12) 2903-2908;

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Candidate Genetic Modifiers of Individual Susceptibility to Renal Cell Carcinoma
Sandrine Longuemaux, Claudine Deloménie, Catherine Gallou, Arnaud Méjean, Monique Vincent-Viry, Raymonde Bouvier, Dominique Droz, Rajagopal Krishnamoorthy, Marie-Madeleine Galteau, Claudine Junien, Christophe Béroud and Jean-Marie Dupret
Cancer Res June 15 1999 (59) (12) 2903-2908;
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