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

被引：128

作者：

Klug, Stefanie J. ^{[1
]}

Ressing, Meike ^{[1
]}

Koenig, Jochem ^{[1
]}

Abba, Martin C. ^{[2
]}

Agorastos, Theodoros ^{[3
]}

Brenna, Sylvia M. F. ^{[4
,5
]}

Ciotti, Marco ^{[6
]}

Das, B. R. ^{[7
]}

Del Mistro, Annarosa ^{[8
]}

Dybikowska, Aleksandra ^{[9
]}

Giuliano, Anna R. ^{[10
]}

Gudleviciene, Zivile ^{[11
]}

Gyllensten, Ulf ^{[12
]}

Haws, Andrea L. F. ^{[13
]}

Helland, Aslaug ^{[14
]}

Herrington, C. Simon ^{[15
]}

Hildesheim, Alan ^{[16
]}

Humbey, Olivier ^{[17
]}

Jee, Sun H. ^{[18
]}

Kim, Jae Weon ^{[19
]}

Madeleine, Margaret M. ^{[20
]}

Menczer, Joseph ^{[21
]}

Ngan, Hextan Y. S. ^{[22
]}

Nishikawa, Akira ^{[23
]}

Niwa, Yoshimitsu ^{[24
]}

Pegoraro, Rosemary ^{[25
]}

Pillai, M. R. ^{[26
]}

Ranzani, Gulielmina ^{[27
]}

Rezza, Giovanni ^{[28
]}

Rosenthal, Adam N. ^{[29
]}

Roychoudhury, Susanta ^{[30
]}

Saranath, Dhananjaya ^{[31
]}

Schmitt, Virginia M. ^{[32
]}

Sengupta, Sharmila ^{[33
]}

Settheetham-Ishida, Wannapa ^{[34
]}

Shirasawa, Hiroshi ^{[35
]}

Snijders, Peter J. F. ^{[36
]}

Stoler, Mark H. ^{[37
]}

Suarez-Rincon, Angel E. ^{[38
]}

Szarka, Krisztina ^{[39
]}

Tachezy, Ruth ^{[40
]}

Ueda, Masatsugu ^{[41
]}

van der Zee, Ate G. J. ^{[42
]}

Doeberitz, Magnus von Knebel ^{[43
]}

Wu, Ming-Tsang ^{[44
,45
,46
]}

Yamashita, Tsuyoshi ^{[47
]}

Zehbe, Ingeborg ^{[48
]}

Blettner, Maria ^{[1
]}

机构：

[1] Johannes Gutenberg Univ Mainz, IMBEI, Univ Med Ctr, D-55101 Mainz, Germany

[2] Natl Univ La Plata, Fac Med Sci, CINIBA, La Plata, Buenos Aires, Argentina

[3] Aristotle Univ Thessaloniki, Dept Obstet & Gynecol 1, Papageorgiou Hosp, GR-54006 Thessaloniki, Greece

[4] City Sao Paolo Univ UNICID, Sch Med, Sao Paulo, Brazil

[5] Leonor Mendes de Barros Matern Hosp, Sao Paulo, Brazil

[6] Univ Hosp Tor Vergata, Mol Virol Lab, Rome, Italy

[7] Super Religare Labs Ltd, Bombay, Maharashtra, India

[8] IRCCS, Ist Oncol Veneto, Padua, Italy

[9] Med Univ Gdansk, Dept Hematol & Transplantal, Gdansk, Poland

[10] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol & Genet, Tampa, FL 33612 USA

[11] Vilnius State Univ, Inst Oncol, Dept Cancerogenesis & Tumor Pathophysiol, Vilnius, Lithuania

[12] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[13] Baylor Coll Med, Houston, TX 77030 USA

[14] Norwegian Radium Hosp, Dept Genet Oncol, Oslo, Norway

[15] Univ St Andrews, Bute Med Sch, St Andrews, Fife, Scotland

[16] NCI, Div Cancer Epidemiol & Genet, Rockville, MD USA

[17] Univ Franche Comte, IBCT, IFR 133, EA 3181, F-25030 Besancon, France

[18] Yonsei Univ, Inst Hlth Promot, Grad Sch Publ Hlth, Seoul 120749, South Korea

[19] Seoul Natl Univ, Dept Obstet & Gynecol, Canc Res Inst, Seoul, South Korea

[20] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA

[21] Med Ctr, Dept Obstet & Gynecol, Gynecol Oncol Unit, Holon, Israel

[22] Queen Marys Hosp, Dept Obstet & Gynecol, Hong Kong, Hong Kong, Peoples R China

[23] NTT E Sapporo Hosp, Dept Obstet & Gynecol, Sapporo, Hokkaido, Japan

[24] Niwa Clin, Nisshin 4580815, Japan

[25] Univ KwaZulu Natal, Dept Clin Med, Nelson R Mandela Sch Med, Congella, South Africa

[26] Rajiv Gandhi Ctr Biotechnol, Thycaud, Kerala, India

[27] Univ Pavia, Dept Genet & Microbiol, I-27100 Pavia, Italy

[28] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy

[29] UCL, EGA Inst Womens Hlth, London, England

[30] CSIR, Inst Biol Chem, Mol & Human Genet Div, Kolkata, India

[31] Reliance Life Sci, Mol Med, Navi Mumbai, India

[32] Pontificia Univ Catolica Rio Grande do Sul, Fac Pharm, Porto Alegre, RS, Brazil

[33] Indian Stat Inst, Human Genet Unit, Kolkata, India

[34] Khon Kaen Univ, Fac Med, Dept Physiol, Khon Kaen, Thailand

[35] Chiba Univ, Grad Sch Med, Dept Mol Virol E2, Chiba, Japan

[36] Vrije Univ Med Ctr, Dept Pathol, Amsterdam, Netherlands

[37] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA

[38] Inst Mexicano Seguro Social, Dept Med Educ & Res, Hosp Gen Reg 45, Guadalajara, Jalisco, Mexico

[39] Univ Debrecen, Dept Med Microbiol, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary

[40] Inst Hematol & Blood Transfus, Natl Reference Lab Papillomaviruses, Dept Expt Virol, CR-12820 Prague, Czech Republic

[41] Osaka Canc Prevent & Detect Ctr, Osaka, Japan

[42] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, NL-9713 AV Groningen, Netherlands

[43] Univ Hosp, Inst Pathol, Heidelberg, Germany

[44] Kaohsiung Med Univ Hosp, Dept Family Med, Kaohsiung, Taiwan

[45] Kaohsiung Med Univ Hosp, Grad Inst Occupat Safety & Hlth, Kaohsiung, Taiwan

[46] Kaohsiung Med Univ, Kaohsiung, Taiwan

[47] Hakodate Municipal Hosp, Dept Obstet & Gynecol, Hakodate, Hokkaido, Japan

[48] Thunder Bay Reg Res Inst, Thunder Bay, ON, Canada

来源：

LANCET ONCOLOGY | 2009年 / 10卷 / 08期

关键词：

SQUAMOUS INTRAEPITHELIAL LESIONS; HUMAN-PAPILLOMAVIRUS TYPE-16; HARDY-WEINBERG EQUILIBRIUM; P53 ARG72PRO POLYMORPHISM; WILD-TYPE P53; HPV INFECTION; RISK-FACTORS; GENOTYPES; WOMEN; METAANALYSIS;

D O I：

10.1016/S1470-2045(09)70187-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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).

引用

页码：772 / 784

页数：13