Article Figures & Data
Figures
- 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.
- 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.
- 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.
- 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.
- 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
- Table 1
Characteristics of studies examining the p53 codon 72 polymorphism and cervical neoplasia
First author year Geographic location Study size DNA source Genotyping methoda Control for ethnicityb Control sampling Case restrictionsa HWE pc Groupa N Cases Controls Storey 1998 United Kingdom Normal 41 Cervix fresh Blood ASP Restriction Convenience None 0.05 Cancer 30 Strickler 1998 Jamaica Normal 30 Blood Blood RFLP Restriction Risk-based None 0.79 Cancer 28 Rosenthal 1998 United Kingdom Normal 246 Cervix archival Blood ASP Restriction Convenience None 0.12 Cancer 50 Minaguchi 1998 Japan Normal 110 Cervix archival Blood ASP Restriction Convenience None 0.69 Cancer 103 Lanham 1998 United Kingdom Normal 250 Cervix fresh Blood ASP None Risk-based (hospital) None 0.97 SIL 265 Cancer 38 Hayes 1998 Netherlands Normal 158 Blood Blood ASP Restriction Convenience None 0.95 SILd 147 Cancerd 25 Helland 1998 Sweden Normal 225 Blood Blood RFLP N.S. Risk-based (population) HPV16/18+ 0.50 SIL 91 Cancer 77 Josefsson 1998 Sweden Normal 626 Cervix archival Cervix archival RFLP Not clear Risk-based (population) None 0.06 SIL 488 Cancer 63 Hildesheim 1998 Costa Rica Normal 123 Blood Blood SSCP N.S. Risk-based (nested) None 0.11 SIL 198 Cancer 49 Hildesheim 1998 United States Normal 217 Cervix fresh Cervix fresh SSCP N.S. Risk-based (nested) None 0.51 SIL 208 Hildesheim 1998 United States Normal 245 Cervix fresh Cervix fresh SSCP N.S. Risk-based None 0.86 SIL 47 Cancer 123 Klaes 1999 Germany Normal 151 Cervix fresh Cervix fresh RFLP Restriction Risk-based None 0.94 Cancer 87 Sonoda 1999 United States Normal 100 Cervix archival Cervix archival DS None Risk-based (hospital) None 0.22 Cancer 105 Szarka 1999 Hungary Normal 87 Cervix fresh Blood ASP Restriction Convenience SIL cases high-risk HPV+ 0.82 SIL 86 Cancer 82 Zehbe 1999 Sweden Normale 626 Cervix archival Cervix archival SSCP N.S. Convenience (previously published) HPV16+ 0.06 SIL 54 Cancer 30 Zehbe 1999 Italy Normal 40 Cervix archival Blood SSCP Restriction Convenience (babies) HPV16+ 0.21 SIL 24 Cancer 28 Ngan 1999 Hong Kong Normal 68 Cervix fresh Cervix fresh ASP Restriction Convenience None 0.01 Cancer 102 Bertorelle 1999 Italy Normalf 100 Cervix fresh Cervix fresh ASP Restriction Risk-based (nested) None 0.31 SIL 104 Wang 1999 Taiwan Normal 56 Cervix fresh Cervix fresh RFLP; DS Restriction Convenience None 0.19 Cancer 58 Yamashita 1999 Japan Normal 252 Cervix archival Cervix archival RFLP Restriction Risk-based None 0.07 SIL 88 Cancer 76 Giannoudis 1999 United Kingdom Normal 30 Cervix archival Cervix archival ASP; RFLP N.S. Convenience None 0.52 SIL 236 Cancer 43 Brady 1999 United Kingdom Normal 74 Blood Blood ASP N.S. Convenience HPV16+ 0.26 Cancer 85 Tachezy 1999 Czech Republic Normal 74 Cervix fresh Cervix fresh ASP Restriction Risk-based None 0.12 Cancer 71 Dybikowska 2000 Poland Normal 52 Cervix fresh Cervix fresh ASP Restriction Risk-based None 0.41 Cancer 44 Wong 2000 Hong Kong Normal None Cervix fresh No controls RFLP; DS Restriction No controls None No controls SIL 10 Cancer 62 Baek 2000 Korea Normal 103 Cervix fresh Blood ASP; RFLP Restriction Convenience None 0.00 Cancer 52 Kim 2000 Korea Normal 181 Blood Blood RFLP Restriction Volunteers HPV16/18+ 0.41 Cancer 181 Dokianakis 2000 Greece Normalf 73 Cervix archival Cervix archival ASP Restriction Convenience HPV16/18/33+ 0.02 SIL 22 Cancer 37 Madeleine 2000 United Kingdom Normal 164 Blood Blood ASP Restriction Risk-based (population) None 0.92 Cancer 111 van Duin 2000 Netherlands Normal 86 Cervixg Cervix archival ASP Not clear Convenience HPV16+ 0.32 SIL 89 Cancer 71 - Table 1A
Continued
First author year Geographic location Study size DNA source Genotyping methoda Control for ethnicityb Control sampling Case restrictionsa HWE pc Groupa N Cases Controls Agorastos 2000 Greece Normal 30 Cervix archival Cervix fresh ASP Restriction Convenience None 0.14 SIL 46 Cancer 12 Malcolm 2000 United States Normal None Cervix archival No controls ASP; RFLP Primarily Caucasian No controls None No controls SIL 264 Cancer 159 Tenti 2000 Italy Normal 140 Cervix archival Cervix fresh ASP; RFLP Restriction Convenience None 0.86 Cancer 101 Makni 2000 Brazil Normalh 73 Cervix fresh Cervix fresh ASP at three labs Adjusted in analysis Risk-based (hospital) None <0.10 Cancer 38 Nishikawa 2000 Japan Normal None Cervix fresh No controls ASP Restriction No controls None No controls SIL 27 Cancer 85 Pegoraro 2000 South Africa Normal 251 Blood Blood ASP Restriction Risk-based None 0.80 Cancer 121 Kucera 2000 Austria Normal 133 Blood Blood Otheri Matching Risk-based None 0.05 SIL 50 Cancer 105 Kim 2001 Korea Normal 100 Blood Blood ASP Restriction Risk-based HPV16+ 0.27 SIL 134 Cancer 100 Zehbe 2001 Sweden Normalf 188 Cervix archival Cervix archival SSCP N.S. Convenience HPV16+ 0.21 SIL 94 Cancer 72 Zehbe 2001 Italy Normalf,j 40 Cervix archival Blood SSCP Restriction Convenience (babies) HPV16+ 0.59 SIL 37 Cancer 43 Gustafsson 2001 Sweden Normalk 36 Cervix archival Cervix archival DS done twice Restriction Convenience None 0.20 SIL 46 Cancer 59 Rezza 2001 Italy Normal 172 Cervix archival Cervix archival RFLP Restriction Risk-based (cohort) None 0.95 SIL 71 Klug 2001 Peru Normal 127 Blood Blood RFLP Adjusted in analysisl Risk-based (hospital) None 0.07 Cancer 119 Andersson 2001 Sweden Normal 188 Cervix archival Cervix fresh SSCP Not clear Convenience None 0.59 Cancer 111 Humbey 2002 France Normal 50 Cervix fresh Cervix fresh DGGE; DS Restriction Risk-based None 0.03 SILd 68 Saranath 2002 India Normal 131 Blood Blood ASP Restriction Convenience None 0.00 Cancer 134 Pegoraro 2002 South Africa Normal 340 Blood Blood ASP Restriction Risk-based (hospital) None 0.85 Cancer 281 Calhoun 2002 United States Normal 108 Cervix fresh Blood DS None Convenience None 0.33 Cancer 127 Suárez-Rincón 2002 Mexico Normal 52 Cervix archival Cervix archival RFLP None Convenience None 0.03 Cancer 38 Bhattacharya 2002 India Normal 201 Cervix fresh Cervix fresh RFLP Restriction Risk-based (neighbors) None 0.14 Cancer 55 Kawamata 2002 Japan Normal 112 Cervix fresh Cervix fresh ASP; DS Restriction Convenience None 0.50 SIL 44 Cancer 44 Pillai 2002 India Normal 110 Blood Blood ASP Restriction Risk-based Nonem 0.45 SIL 128 Cancer 183 Arbel-Alon 2002 Israel Normal 162 Blood Blood ASP Adjustmentn Risk-based (population) None 0.00 Cancer 23 Nagpal 2002 India Normal 29 Cervix fresh Cervix fresh ASP Restriction Risk-based (hospital) None 0.03 SIL 39 Cancer 71 -
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.
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b N.S., not specified.
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c P for χ-square test of statistically significant deviations from Hardy-Weinberg equilibrium (HWE).
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d Cases not histologically confirmed.
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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.
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f Controls all HPV-negative.
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g Archival samples used for cancer cases; Fresh cervical samples used for SIL cases.
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h HPV-positive controls over-sampled.
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i Allele-specific hybridization done after PCR step.
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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.
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k Controls histologically defined as non-neoplastic (normal cervicitis, hyperplasia, metaplasia, condyloma) - high-risk HPV-positive controls preferentially selected.
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l In meta-analysis and regression, we used the crude OR; thus, Klug et al categorized as not having controlled for race.
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m Of the HPV-positive cases, only the HPV16-positive included but HPV negative also included.
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n We calculated adjusted OR from the raw data provided in the article.
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- 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 characteristic Contrast Ratio of odds ratios (95% confidence interval) ICC (n = 24) SCC (n = 22) HSIL (n = 22) LSIL (n = 18) Year of publication 2000s vs. 1990s 0.89 (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 study Europe vs. Other regions 1.00 (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 equilibrium Not in equilibrium vs. in equilibrium 1.46 (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 group Convenience vs. risk-based 1.26 (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/race Uncontrolled vs. controlled 0.91 (0.63–1.32) 0.78 (0.46–1.31) 0.90 (0.69–1.17) 0.76 (0.54–1.09) Genotyping method utilized Allele-specific PCR vs. other 1.35 (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 method 1.15 (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 group High-risk HPV+ vs. unrestricted 0.78 (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 group Cervical tissue vs. blood 1.15 (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 tissue 1.47 (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 controls Archival vs. fresh tissue 1.29 (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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Volume 13, Issue 1
