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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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p53 Codon 72 Polymorphism and Cervical Neoplasia

A Meta-Analysis Review

Anita Koushik, Robert W. Platt and Eduardo L. Franco
Anita Koushik
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Robert W. Platt
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Eduardo L. Franco
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DOI: 10.1158/1055-9965.EPI-083-3 Published January 2004
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  • Fig. 1.
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    Fig. 1.

    Odds ratios (OR) and 95% confidence intervals (CI) from studies examining the association between invasive cervical cancer (histology not specified) and the p53 codon 72 genotype (Arg/Arg versus Arg/Pro or Pro/Pro). The center of each square represents the OR, the area of the square is the inverse of the variance and thus the weight used in the meta-analysis, and the horizontal line indicates the 95% CI. The summary OR is represented by the diamond, where the center of the diamond indicates the OR and the ends of the diamond correspond to the 95% CI. aCosta Rica.

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    Fig. 2.

    Odds ratios (OR) and 95% confidence intervals (CI) from studies examining the association between squamous cell cervical cancer and the p53 codon 72 genotype (Arg/Arg versus Arg/Pro or Pro/Pro). The center of each square represents the OR, the area of the square is the inverse of the variance and thus the weight used in the meta-analysis, and the horizontal line indicates the 95% CI. The summary OR is represented by the diamond, where the center of the diamond indicates the OR, and the ends of the diamond correspond to the 95% CI. aEastern United States; bItaly; cSweden; dSweden; eItaly.

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    Fig. 3.

    Odds ratios (OR) and 95% confidence intervals (CI) from studies examining the association between cervical adenocarcinoma and the p53 codon 72 genotype (Arg/Arg versus Arg/Pro or Pro/Pro). The center of each square represents the OR, the area of the square is the inverse of the variance and thus the weight used in the meta-analysis, and the horizontal line indicates the 95% CI. The summary OR is represented by the diamond, where the center of the diamond indicates the OR and the ends of the diamond correspond to the 95% CI. aEastern United States.

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    Fig. 4.

    Odds ratios (OR) and 95% confidence intervals (CI) from studies examining the association between high-grade squamous intraepithelial lesions and the p53 codon 72 genotype (Arg/Arg versus Arg/Pro or Pro/Pro). The center of each square represents the OR, the area of the square is the inverse of the variance and thus the weight used in the meta-analysis, and the horizontal line indicates the 95% CI. The summary OR is represented by the diamond, where the center of the diamond indicates the OR and the ends of the diamond correspond to the 95% CI. aCosta Rica; bPortland; cEastern United States; dItaly; eSweden; fSweden; gItaly.

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    Fig. 5.

    Odds ratios (OR) and 95% confidence intervals (CI) from studies examining the association between low-grade squamous intraepithelial lesions and the p53 codon 72 genotype (Arg/Arg versus Arg/Pro or Pro/Pro). The center of each square represents the OR, the area of the square is the inverse of the variance and thus the weight used in the meta-analysis, and the horizontal line indicates the 95% CI. The summary OR is represented by the diamond, where the center of the diamond indicates the OR and the ends of the diamond correspond to the 95% CI. aCosta Rica; bPortland; cSweden; dItaly.

Tables

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  • Table 1

    Characteristics of studies examining the p53 codon 72 polymorphism and cervical neoplasia

    First author yearGeographic locationStudy sizeDNA sourceGenotyping methodaControl for ethnicitybControl samplingCase restrictionsaHWE pc
    GroupaNCasesControls
    Storey 1998United KingdomNormal41Cervix freshBloodASPRestrictionConvenienceNone0.05
    Cancer30
    Strickler 1998JamaicaNormal30BloodBloodRFLPRestrictionRisk-basedNone0.79
    Cancer28
    Rosenthal 1998United KingdomNormal246Cervix archivalBloodASPRestrictionConvenienceNone0.12
    Cancer50
    Minaguchi 1998JapanNormal110Cervix archivalBloodASPRestrictionConvenienceNone0.69
    Cancer103
    Lanham 1998United KingdomNormal250Cervix freshBloodASPNoneRisk-based (hospital)None0.97
    SIL265
    Cancer38
    Hayes 1998NetherlandsNormal158BloodBloodASPRestrictionConvenienceNone0.95
    SILd147
    Cancerd25
    Helland 1998SwedenNormal225BloodBloodRFLPN.S.Risk-based (population)HPV16/18+0.50
    SIL91
    Cancer77
    Josefsson 1998SwedenNormal626Cervix archivalCervix archivalRFLPNot clearRisk-based (population)None0.06
    SIL488
    Cancer63
    Hildesheim 1998Costa RicaNormal123BloodBloodSSCPN.S.Risk-based (nested)None0.11
    SIL198
    Cancer49
    Hildesheim 1998United StatesNormal217Cervix freshCervix freshSSCPN.S.Risk-based (nested)None0.51
    SIL208
    Hildesheim 1998United StatesNormal245Cervix freshCervix freshSSCPN.S.Risk-basedNone0.86
    SIL47
    Cancer123
    Klaes 1999GermanyNormal151Cervix freshCervix freshRFLPRestrictionRisk-basedNone0.94
    Cancer87
    Sonoda 1999United StatesNormal100Cervix archivalCervix archivalDSNoneRisk-based (hospital)None0.22
    Cancer105
    Szarka 1999HungaryNormal87Cervix freshBloodASPRestrictionConvenienceSIL cases high-risk HPV+0.82
    SIL86
    Cancer82
    Zehbe 1999SwedenNormale626Cervix archivalCervix archivalSSCPN.S.Convenience (previously published)HPV16+0.06
    SIL54
    Cancer30
    Zehbe 1999ItalyNormal40Cervix archivalBloodSSCPRestrictionConvenience (babies)HPV16+0.21
    SIL24
    Cancer28
    Ngan 1999Hong KongNormal68Cervix freshCervix freshASPRestrictionConvenienceNone0.01
    Cancer102
    Bertorelle 1999ItalyNormalf100Cervix freshCervix freshASPRestrictionRisk-based (nested)None0.31
    SIL104
    Wang 1999TaiwanNormal56Cervix freshCervix freshRFLP; DSRestrictionConvenienceNone0.19
    Cancer58
    Yamashita 1999JapanNormal252Cervix archivalCervix archivalRFLPRestrictionRisk-basedNone0.07
    SIL88
    Cancer76
    Giannoudis 1999United KingdomNormal30Cervix archivalCervix archivalASP; RFLPN.S.ConvenienceNone0.52
    SIL236
    Cancer43
    Brady 1999United KingdomNormal74BloodBloodASPN.S.ConvenienceHPV16+0.26
    Cancer85
    Tachezy 1999Czech RepublicNormal74Cervix freshCervix freshASPRestrictionRisk-basedNone0.12
    Cancer71
    Dybikowska 2000PolandNormal52Cervix freshCervix freshASPRestrictionRisk-basedNone0.41
    Cancer44
    Wong 2000Hong KongNormalNoneCervix freshNo controlsRFLP; DSRestrictionNo controlsNoneNo controls
    SIL10
    Cancer62
    Baek 2000KoreaNormal103Cervix freshBloodASP; RFLPRestrictionConvenienceNone0.00
    Cancer52
    Kim 2000KoreaNormal181BloodBloodRFLPRestrictionVolunteersHPV16/18+0.41
    Cancer181
    Dokianakis 2000GreeceNormalf73Cervix archivalCervix archivalASPRestrictionConvenienceHPV16/18/33+0.02
    SIL22
    Cancer37
    Madeleine 2000United KingdomNormal164BloodBloodASPRestrictionRisk-based (population)None0.92
    Cancer111
    van Duin 2000NetherlandsNormal86CervixgCervix archivalASPNot clearConvenienceHPV16+0.32
    SIL89
    Cancer71
  • Table 1A

    Continued

    First author yearGeographic locationStudy sizeDNA sourceGenotyping methodaControl for ethnicitybControl samplingCase restrictionsaHWE pc
    GroupaNCasesControls
    Agorastos 2000GreeceNormal30Cervix archivalCervix freshASPRestrictionConvenienceNone0.14
    SIL46
    Cancer12
    Malcolm 2000United StatesNormalNoneCervix archivalNo controlsASP; RFLPPrimarily CaucasianNo controlsNoneNo controls
    SIL264
    Cancer159
    Tenti 2000ItalyNormal140Cervix archivalCervix freshASP; RFLPRestrictionConvenienceNone0.86
    Cancer101
    Makni 2000BrazilNormalh73Cervix freshCervix freshASP at three labsAdjusted in analysisRisk-based (hospital)None<0.10
    Cancer38
    Nishikawa 2000JapanNormalNoneCervix freshNo controlsASPRestrictionNo controlsNoneNo controls
    SIL27
    Cancer85
    Pegoraro 2000South AfricaNormal251BloodBloodASPRestrictionRisk-basedNone0.80
    Cancer121
    Kucera 2000AustriaNormal133BloodBloodOtheriMatchingRisk-basedNone0.05
    SIL50
    Cancer105
    Kim 2001KoreaNormal100BloodBloodASPRestrictionRisk-basedHPV16+0.27
    SIL134
    Cancer100
    Zehbe 2001SwedenNormalf188Cervix archivalCervix archivalSSCPN.S.ConvenienceHPV16+0.21
    SIL94
    Cancer72
    Zehbe 2001ItalyNormalf,j40Cervix archivalBloodSSCPRestrictionConvenience (babies)HPV16+0.59
    SIL37
    Cancer43
    Gustafsson 2001SwedenNormalk36Cervix archivalCervix archivalDS done twiceRestrictionConvenienceNone0.20
    SIL46
    Cancer59
    Rezza 2001ItalyNormal172Cervix archivalCervix archivalRFLPRestrictionRisk-based (cohort)None0.95
    SIL71
    Klug 2001PeruNormal127BloodBloodRFLPAdjusted in analysislRisk-based (hospital)None0.07
    Cancer119
    Andersson 2001SwedenNormal188Cervix archivalCervix freshSSCPNot clearConvenienceNone0.59
    Cancer111
    Humbey 2002FranceNormal50Cervix freshCervix freshDGGE; DSRestrictionRisk-basedNone0.03
    SILd68
    Saranath 2002IndiaNormal131BloodBloodASPRestrictionConvenienceNone0.00
    Cancer134
    Pegoraro 2002South AfricaNormal340BloodBloodASPRestrictionRisk-based (hospital)None0.85
    Cancer281
    Calhoun 2002United StatesNormal108Cervix freshBloodDSNoneConvenienceNone0.33
    Cancer127
    Suárez-Rincón 2002MexicoNormal52Cervix archivalCervix archivalRFLPNoneConvenienceNone0.03
    Cancer38
    Bhattacharya 2002IndiaNormal201Cervix freshCervix freshRFLPRestrictionRisk-based (neighbors)None0.14
    Cancer55
    Kawamata 2002JapanNormal112Cervix freshCervix freshASP; DSRestrictionConvenienceNone0.50
    SIL44
    Cancer44
    Pillai 2002IndiaNormal110BloodBloodASPRestrictionRisk-basedNonem0.45
    SIL128
    Cancer183
    Arbel-Alon 2002IsraelNormal162BloodBloodASPAdjustmentnRisk-based (population)None0.00
    Cancer23
    Nagpal 2002IndiaNormal29Cervix freshCervix freshASPRestrictionRisk-based (hospital)None0.03
    SIL39
    Cancer71
    • a SIL, Squamous intraepithelial lesions; ASP, allele-specific PCR; RFLP, restriction fragment length polymorphism; SSCP, single strand conformation polymorphism; DS, DNA sequencing; DGGE, denaturant gradient gel electrophoresis; HPV, human papillomavirus.

    • b N.S., not specified.

    • c P for χ-square test of statistically significant deviations from Hardy-Weinberg equilibrium (HWE).

    • d Cases not histologically confirmed.

    • e Same controls as in Josefsson 1998; sensitivity analyses excluding either or both studies did not change the results of the meta-analyses or regressions.

    • f Controls all HPV-negative.

    • g Archival samples used for cancer cases; Fresh cervical samples used for SIL cases.

    • h HPV-positive controls over-sampled.

    • i Allele-specific hybridization done after PCR step.

    • j Same controls as in Zehbe 1999; sensitivity analyses excluding either or both studies did not change the results of the meta-analyses or regressions.

    • k Controls histologically defined as non-neoplastic (normal cervicitis, hyperplasia, metaplasia, condyloma) - high-risk HPV-positive controls preferentially selected.

    • l In meta-analysis and regression, we used the crude OR; thus, Klug et al categorized as not having controlled for race.

    • m Of the HPV-positive cases, only the HPV16-positive included but HPV negative also included.

    • n We calculated adjusted OR from the raw data provided in the article.

  • Table 2

    Contribution of selected factors on the magnitude of the ORsa for the association between the p53 codon 72 polymorphism and cervical neoplasia: results from meta-regression

    Study design characteristicContrastRatio of odds ratios (95% confidence interval)
    ICC (n = 24)SCC (n = 22)HSIL (n = 22)LSIL (n = 18)
    Year of publication2000s vs. 1990s0.89 (0.64–1.24)1.40 (0.85–2.30)1.13 (0.86–1.49)1.23 (0.86–1.78)
    Geographical region of studyEurope vs. Other regions1.00 (0.68–1.45)0.94 (0.56–1.61)1.09 (0.84–1.41)0.86 (0.59–1.26)
    Control group in Hardy-Weinberg equilibriumNot in equilibrium vs. in equilibrium1.46 (1.05–2.02)2.28 (1.34–3.86)1.23 (0.96–1.57)1.05 (0.61–1.80)
    Sampling of control groupConvenience vs. risk-based1.26 (0.89–1.77)1.43 (0.89–2.30)0.94 (0.72–1.23)1.11 (0.75–1.64)
    Control for ethnicity/raceUncontrolled vs. controlled0.91 (0.63–1.32)0.78 (0.46–1.31)0.90 (0.69–1.17)0.76 (0.54–1.09)
    Genotyping method utilizedAllele-specific PCR vs. other1.35 (0.98–1.86)1.06 (0.63–1.76)0.99 (0.76–1.28)0.99 (0.68–1.42)
    One method vs. > one method1.15 (0.67–1.98)1.01 (0.49–2.07)1.37 (0.84–2.25)1.07 (0.62–1.84)
    Restriction of case groupHigh-risk HPV+ vs. unrestricted0.78 (0.53–1.14)1.99 (1.24–3.19)1.03 (0.79–1.35)0.90 (0.58–1.41)
    DNA source used for case groupCervical tissue vs. blood1.15 (0.82–1.61)0.92 (0.51–1.65)0.99 (0.76–1.31)1.33 (0.82–2.16)
    Archival vs. fresh tissue1.47 (0.86–2.54)0.98 (0.46–2.10)1.35 (1.02–1.80)1.40 (0.95–2.09)
    DNA source used for controlsArchival vs. fresh tissue1.29 (0.63–2.64)1.25 (0.62–2.51)1.02 (0.73–1.45)0.89 (0.57–1.39)
    • a OR, odds ratio; ICC, invasive cervical cancer; SCC, squamous cell carcinoma; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion.

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Cancer Epidemiology Biomarkers & Prevention: 13 (1)
January 2004
Volume 13, Issue 1
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p53 Codon 72 Polymorphism and Cervical Neoplasia
Anita Koushik, Robert W. Platt and Eduardo L. Franco
Cancer Epidemiol Biomarkers Prev January 1 2004 (13) (1) 11-22; DOI: 10.1158/1055-9965.EPI-083-3

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p53 Codon 72 Polymorphism and Cervical Neoplasia
Anita Koushik, Robert W. Platt and Eduardo L. Franco
Cancer Epidemiol Biomarkers Prev January 1 2004 (13) (1) 11-22; DOI: 10.1158/1055-9965.EPI-083-3
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