TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies

Stefanie J Klug; Meike Ressing; Jochem Koenig; Martin C Abba; Theodoros Agorastos; Sylvia M F Brenna; Marco Ciotti; B R Das; Annarosa Del Mistro; Aleksandra Dybikowska; Anna R Giuliano; Zivile Gudleviciene; Ulf Gyllensten; Andrea L F Haws; Aslaug Helland; C Simon Herrington; Alan Hildesheim; Olivier Humbey; Sun H Jee; Jae Weon Kim; Margaret M Madeleine; Joseph Menczer; Hextan Y S Ngan; Akira Nishikawa; Yoshimitsu Niwa; Rosemary Pegoraro; M R Pillai; Gulielmina Ranzani; Giovanni Rezza; Adam N Rosenthal; Susanta Roychoudhury; Dhananjaya Saranath; Virginia M Schmitt; Sharmila Sengupta; Wannapa Settheetham-Ishida; Hiroshi Shirasawa; Peter J F Snijders; Mark H Stoler; Angel E Suárez-Rincón; Krisztina Szarka; Ruth Tachezy; Masatsugu Ueda; Ate G J van der Zee; Magnus von Knebel Doeberitz; Ming-Tsang Wu; Tsuyoshi Yamashita; Ingeborg Zehbe; Maria Blettner

doi:10.1016/S1470-2045(09)70187-1

TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies

Stefanie J Klug, Meike Ressing, Jochem Koenig, Martin C Abba, Theodoros Agorastos, Sylvia M F Brenna, Marco Ciotti, B R Das, Annarosa Del Mistro, Aleksandra Dybikowska, Anna R Giuliano, Zivile Gudleviciene, Ulf Gyllensten, Andrea L F Haws, Aslaug Helland, C Simon Herrington, Alan Hildesheim, Olivier Humbey, Sun H Jee, Jae Weon KimMargaret M Madeleine, Joseph Menczer, Hextan Y S Ngan, Akira Nishikawa, Yoshimitsu Niwa, Rosemary Pegoraro, M R Pillai, Gulielmina Ranzani, Giovanni Rezza, Adam N Rosenthal, Susanta Roychoudhury, Dhananjaya Saranath, Virginia M Schmitt, Sharmila Sengupta, Wannapa Settheetham-Ishida, Hiroshi Shirasawa, Peter J F Snijders, Mark H Stoler, Angel E Suárez-Rincón, Krisztina Szarka, Ruth Tachezy, Masatsugu Ueda, Ate G J van der Zee, Magnus von Knebel Doeberitz, Ming-Tsang Wu, Tsuyoshi Yamashita, Ingeborg Zehbe, Maria Blettner

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer.

METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype.

FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes).

INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.

FUNDING: German Research Foundation (DFG).

Original language	English
Pages (from-to)	772-84
Number of pages	13
Journal	The Lancet Oncology
Volume	10
Issue number	8
DOIs	https://doi.org/10.1016/S1470-2045(09)70187-1
Publication status	Published - Aug 2009

Keywords

Adolescent
Adult
Aged
Female
Genes, p53
Genetic Predisposition to Disease
Humans
Middle Aged
Papillomavirus Infections
Polymorphism, Genetic
Uterine Cervical Neoplasms
Young Adult

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10.1016/S1470-2045(09)70187-1

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Klug, S. J., Ressing, M., Koenig, J., Abba, M. C., Agorastos, T., Brenna, S. M. F., Ciotti, M., Das, B. R., Del Mistro, A., Dybikowska, A., Giuliano, A. R., Gudleviciene, Z., Gyllensten, U., Haws, A. L. F., Helland, A., Herrington, C. S., Hildesheim, A., Humbey, O., Jee, S. H., ... Blettner, M. (2009). TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. The Lancet Oncology, 10(8), 772-84. https://doi.org/10.1016/S1470-2045(09)70187-1

@article{f42fe1a7aaef4a318768420f231e959f,

title = "TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies",

abstract = "BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer.METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype.FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes).INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.FUNDING: German Research Foundation (DFG).",

keywords = "Adolescent, Adult, Aged, Female, Genes, p53, Genetic Predisposition to Disease, Humans, Middle Aged, Papillomavirus Infections, Polymorphism, Genetic, Uterine Cervical Neoplasms, Young Adult",

author = "Klug, {Stefanie J} and Meike Ressing and Jochem Koenig and Abba, {Martin C} and Theodoros Agorastos and Brenna, {Sylvia M F} and Marco Ciotti and Das, {B R} and {Del Mistro}, Annarosa and Aleksandra Dybikowska and Giuliano, {Anna R} and Zivile Gudleviciene and Ulf Gyllensten and Haws, {Andrea L F} and Aslaug Helland and Herrington, {C Simon} and Alan Hildesheim and Olivier Humbey and Jee, {Sun H} and Kim, {Jae Weon} and Madeleine, {Margaret M} and Joseph Menczer and Ngan, {Hextan Y S} and Akira Nishikawa and Yoshimitsu Niwa and Rosemary Pegoraro and Pillai, {M R} and Gulielmina Ranzani and Giovanni Rezza and Rosenthal, {Adam N} and Susanta Roychoudhury and Dhananjaya Saranath and Schmitt, {Virginia M} and Sharmila Sengupta and Wannapa Settheetham-Ishida and Hiroshi Shirasawa and Snijders, {Peter J F} and Stoler, {Mark H} and Su{\'a}rez-Rinc{\'o}n, {Angel E} and Krisztina Szarka and Ruth Tachezy and Masatsugu Ueda and {van der Zee}, {Ate G J} and {von Knebel Doeberitz}, Magnus and Ming-Tsang Wu and Tsuyoshi Yamashita and Ingeborg Zehbe and Maria Blettner",

year = "2009",

month = aug,

doi = "10.1016/S1470-2045(09)70187-1",

language = "English",

volume = "10",

pages = "772--84",

journal = "The Lancet Oncology",

issn = "1470-2045",

publisher = "Lancet Publishing Group",

number = "8",

}

Klug, SJ, Ressing, M, Koenig, J, Abba, MC, Agorastos, T, Brenna, SMF, Ciotti, M, Das, BR, Del Mistro, A, Dybikowska, A, Giuliano, AR, Gudleviciene, Z, Gyllensten, U, Haws, ALF, Helland, A, Herrington, CS, Hildesheim, A, Humbey, O, Jee, SH, Kim, JW, Madeleine, MM, Menczer, J, Ngan, HYS, Nishikawa, A, Niwa, Y, Pegoraro, R, Pillai, MR, Ranzani, G, Rezza, G, Rosenthal, AN, Roychoudhury, S, Saranath, D, Schmitt, VM, Sengupta, S, Settheetham-Ishida, W, Shirasawa, H, Snijders, PJF, Stoler, MH, Suárez-Rincón, AE, Szarka, K, Tachezy, R, Ueda, M, van der Zee, AGJ, von Knebel Doeberitz, M, Wu, M-T, Yamashita, T, Zehbe, I & Blettner, M 2009, 'TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies', The Lancet Oncology, vol. 10, no. 8, pp. 772-84. https://doi.org/10.1016/S1470-2045(09)70187-1

TY - JOUR

T1 - TP53 codon 72 polymorphism and cervical cancer

T2 - a pooled analysis of individual data from 49 studies

AU - Klug, Stefanie J

AU - Ressing, Meike

AU - Koenig, Jochem

AU - Abba, Martin C

AU - Agorastos, Theodoros

AU - Brenna, Sylvia M F

AU - Ciotti, Marco

AU - Das, B R

AU - Del Mistro, Annarosa

AU - Dybikowska, Aleksandra

AU - Giuliano, Anna R

AU - Gudleviciene, Zivile

AU - Gyllensten, Ulf

AU - Haws, Andrea L F

AU - Helland, Aslaug

AU - Herrington, C Simon

AU - Hildesheim, Alan

AU - Humbey, Olivier

AU - Jee, Sun H

AU - Kim, Jae Weon

AU - Madeleine, Margaret M

AU - Menczer, Joseph

AU - Ngan, Hextan Y S

AU - Nishikawa, Akira

AU - Niwa, Yoshimitsu

AU - Pegoraro, Rosemary

AU - Pillai, M R

AU - Ranzani, Gulielmina

AU - Rezza, Giovanni

AU - Rosenthal, Adam N

AU - Roychoudhury, Susanta

AU - Saranath, Dhananjaya

AU - Schmitt, Virginia M

AU - Sengupta, Sharmila

AU - Settheetham-Ishida, Wannapa

AU - Shirasawa, Hiroshi

AU - Snijders, Peter J F

AU - Stoler, Mark H

AU - Suárez-Rincón, Angel E

AU - Szarka, Krisztina

AU - Tachezy, Ruth

AU - Ueda, Masatsugu

AU - van der Zee, Ate G J

AU - von Knebel Doeberitz, Magnus

AU - Wu, Ming-Tsang

AU - Yamashita, Tsuyoshi

AU - Zehbe, Ingeborg

AU - Blettner, Maria

PY - 2009/8

Y1 - 2009/8

N2 - BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer.METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype.FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes).INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.FUNDING: German Research Foundation (DFG).

AB - BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer.METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype.FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes).INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.FUNDING: German Research Foundation (DFG).

KW - Adolescent

KW - Adult

KW - Aged

KW - Female

KW - Genes, p53

KW - Genetic Predisposition to Disease

KW - Humans

KW - Middle Aged

KW - Papillomavirus Infections

KW - Polymorphism, Genetic

KW - Uterine Cervical Neoplasms

KW - Young Adult

U2 - 10.1016/S1470-2045(09)70187-1

DO - 10.1016/S1470-2045(09)70187-1

M3 - Article

C2 - 19625214

VL - 10

SP - 772

EP - 784

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 8

ER -

TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies

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Keywords

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