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BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

Authors: Paola Gallì, Gabriella Cadoni, Mariangela Volante, Emma De Feo, Rosarita Amore, Arianna Giorgio, Dario Arzani, Gaetano Paludetti, Gualtiero Ricciardi, Stefania Boccia

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.

Methods

Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms.

Results

We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the p53 exon 4-p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).

Conclusion

Our study provides for the first time evidence that individuals carrying p53 exon 4 and p53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of p73 exon 2 G4C14-to-A4T14 and p53 intron 3 variant allele. Larger studies are required to confirm these findings.
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Literature
1.
Pisani P, Parkin DM, Bray F, Ferlay J: Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 1999, 83: 18-29. 10.1002/(SICI)1097-0215(19990924)83:1<18::AID-IJC5>3.0.CO;2-M.CrossRefPubMed
2.
Altieri A, Garavello W, Bosetti C, Gallus S, La Vecchia C: Alcohol consumption and risk of laryngeal cancer. Oral Oncol. 2005, 41 (10): 956-65. 10.1016/j.oraloncology.2005.02.004.CrossRefPubMed
3.
Hashibe M, Boffetta P, Zaridze D, Shangina O, Szeszenia-Dabrowska N, Mates D, Fabiánová E, Rudnai P, Brennan P: Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the supraglottis and glottis in Central Europe. Am J Epidemiol. 2007, 165 (7): 814-20. 10.1093/aje/kwk066.CrossRefPubMed
4.
Tran N, Rose BR, O'Brien CJ: Role of human papillomavirus in the etiology of head and neck cancer. Head Neck. 2007, 29 (1): 64-70. 10.1002/hed.20460.CrossRefPubMed
5.
Boccia S, Cadoni G, Sayed-Tabatabaei FA, Volante M, Arzani D, De Lauretis A, Cattel C, Almadori G, van Duijn CM, Paludetti G, Ricciardi G: CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer. J Cancer Res Clin Oncol. 2008, 134 (1): 93-100. 10.1007/s00432-007-0254-5.CrossRefPubMed
6.
Pavia M, Pileggi C, Nobile CG, Angelillo IF: Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr. 2006, 83 (5): 1126-34.PubMed
7.
Jefferies S, Foulkes WD: Genetic mechanisms in squamous cell carcinoma of the head and neck. Oral Oncol. 2001, 37 (2): 115-26. 10.1016/S1368-8375(00)00065-8.CrossRefPubMed
8.
Vogelstein B, Lane D, Levine AJ: Surfing the p53 network. Nature. 2000, 408 (6810): 307-10. 10.1038/35042675.CrossRefPubMed
9.
Matakidou A, Eisen T, Houlston RS: TP53 polymorphisms and lung cancer risk: a systematic review and meta-analysis. Mutagenesis. 2003, 18 (4): 377-85. 10.1093/mutage/geg008.CrossRefPubMed
10.
Li G, Sturgis EM, Wang LE, Chamberlain RM, Amos CI, Spitz MR, El-Naggar AK, Hong WK, Wei Q: Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of squamous cell carcinoma of the head and neck. Carcinogenesis. 2004, 25 (10): 1911-6. 10.1093/carcin/bgh197.CrossRefPubMed
11.
Hsieh LL, Huang TH, Chen IH, Liao CT, Wang HM, Lai CH, Liou SH, Chang JT, Cheng AJ: p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan. Br J Cancer. 2005, 92 (1): 30-5. 10.1038/sj.bjc.6602271.CrossRefPubMed
12.
Wu X, Zhao H, Amos CI, Shete S, Makan N, Hong WK, Kadlubar FF, Spitz MR: p53 Genotypes and Haplotypes Associated With Lung Cancer Susceptibility and Ethnicity. J Natl Cancer Inst. 2002, 94 (9): 681-90.CrossRefPubMed
13.
McWilliams JE, Evans AJ, Beer TM, Andersen PE, Cohen JI, Everts EC, Henner WD: Genetic polymorphisms in head and neck cancer risk. Head Neck. 2000, 22 (6): 609-17. 10.1002/1097-0347(200009)22:6<609::AID-HED10>3.0.CO;2-L.CrossRefPubMed
14.
Hamel N, Black MJ, Ghadirian P, Foulkes WD: No association between p53 codon 72 polymorphism and risk of squamous cell carcinoma of the head and neck. Br J Cancer. 2000, 82 (4): 757-9. 10.1054/bjoc.1999.0993.CrossRefPubMedPubMedCentral
15.
Shen H, Zheng Y, Sturgis EM, Spitz MR, Wei Q: p53 codon 72 polymorphism and risk of squamous cell carcinoma of the head and neck: a case-control study. Cancer Lett. 2002, 183 (2): 123-30. 10.1016/S0304-3835(02)00117-9.CrossRefPubMed
16.
Tsai MH, Lin CD, Hsieh YY, Chang FC, Tsai FJ, Chen WC, Tsai CH: Prognostic significance of the proline form of p53 codon 72 polymorphism in nasopharyngeal carcinoma. Laryngoscope. 2002, 112 (1): 116-9. 10.1097/00005537-200201000-00020.CrossRefPubMed
17.
Wang-Gohrke S, Weikel W, Risch H, Vesprini D, Abrahamson J, Lerman C, Godwin A, Moslehi R, Olipade O, Brunet JS, Stickeler E, Kieback DG, Kreienberg R, Weber B, Narod SA, Runnebaum IB: Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations. Br J Cancer. 1999, 81 (1): 179-83. 10.1038/sj.bjc.6690669.CrossRefPubMedPubMedCentral
18.
Sprague BL, Trentham-Dietz A, Garcia-Closas M, Newcomb PA, Titus-Ernstoff L, Hampton JM, Chanock SJ, Haines JL, Egan KM: Genetic variation in TP53 and risk of breast cancer in a population-based case control study. Carcinogenesis. 2007, 28 (8): 1680-6. 10.1093/carcin/bgm097.CrossRefPubMed
19.
Peller S, Halevy A, Slutzki S, Kopilova Y, Rotter V: p53 mutations in matched primary and metastatic human tumors. Mol Carcinog. 1995, 13 (3): 166-72. 10.1002/mc.2940130306.CrossRefPubMed
20.
Takahashi H, Ichimiya S, Nimura Y, Watanabe M, Furusato M, Wakui S, Yatani R, Aizawa S, Nakagawara A: Mutation, allelotyping, and transcription analyses of the p73 gene in prostatic carcinoma. Cancer Res. 1998, 58 (10): 2076-7.PubMed
21.
Nomoto S, Haruki N, Kondo M, Konishi H, Takahashi T, Takahashi T, Takahashi T: Search for mutations and examination of allelic expression imbalance of the p73 gene at 1p36.33 in human lung cancers. Cancer Res. 1998, 58 (7): 1380-3.PubMed
22.
Schabath MB, Wu X, Wei Q, Li G, Gu J, Spitz MR: Combined effects of the p53 and 73 polymorphisms on lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2006, 15 (1): 158-61. 10.1158/1055-9965.EPI-05-0622.CrossRefPubMed
23.
Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D: Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997, 90 (4): 809-19. 10.1016/S0092-8674(00)80540-1.CrossRefPubMed
24.
Li G, Wang LE, Chamberlain RM, Amos CI, Spitz MR, Wei Q: p73 G4C14-to-A4T14 polymorphism and risk of lung cancer. Cancer Res. 2004, 64 (19): 6863-6. 10.1158/0008-5472.CAN-04-1804.CrossRefPubMed
25.
Niwa Y, Hirose K, Matsuo K, Tajima K, Ikoma Y, Nakanishi T, Nawa A, Kuzuya K, Tamakoshi A, Hamajima N: Association of p73 G4C14-to-A4T14 polymorphism at exon 2 and p53 Arg72Pro polymorphism with the risk of endometrial cancer in Japanese subjects. Cancer Lett. 2005, 219 (2): 183-90. 10.1016/j.canlet.2004.10.018.CrossRefPubMed
26.
Ryan BM, McManus R, Daly JS, Carton E, Keeling PW, Reynolds JV, Kelleher D: A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma. Br J Cancer. 2001, 85 (10): 1499-503. 10.1054/bjoc.2001.2066.CrossRefPubMedPubMedCentral
27.
Hu Z, Miao X, Ma H, Tan W, Wang X, Lu D, Wei Q, Lin D, Shen H: Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population. Int J Cancer. 2005, 114 (3): 455-60. 10.1002/ijc.20746.CrossRefPubMed
28.
Sullivan A, Syed N, Gasco M, Bergamaschi D, Trigiante G, Attard M, Hiller L, Farrell PJ, Smith P, Lu X, Crook T: Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo. Oncogene. 2004, 23 (19): 3328-37. 10.1038/sj.onc.1207428.CrossRefPubMed
29.
Wang YC, Chen CY, Chen SK, Chang YY, Lin P: p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis. Clin Cancer Res. 1999, 5 (1): 129-34.PubMed
30.
Starinsky S, Figer A, Ben-Asher E, Geva R, Flex D, Fidder HH, Zidan J, Lancet D, Friedman E: Genotype phenotype correlations in Israeli colorectal cancer patients. Int J Cancer. 2005, 114 (1): 58-73. 10.1002/ijc.20645.CrossRefPubMed
31.
Toyama T, Zhang Z, Nishio M, Hamaguchi M, Kondo N, Iwase H, Iwata H, Takahashi S, Yamashita H, Fujii Y: Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients. Breast Cancer Res. 2007, 9 (3):
32.
Pfeifer D, Arbman G, Sun XF: Polymorphism of the p73 gene in relation to colorectal cancer risk and survival. Carcinogenesis. 2005, 26 (1): 103-7. 10.1093/carcin/bgh305.CrossRefPubMed
33.
Sobin LH, Wittekind C: TNM Classification of malignant tumors. 1997, New York: John Wiley & Sons, 5
34.
Terwilliger J, Ott J: Handbook of Human Genetic Linkage. 1994, John Hopkins University Press, Baltimore
35.
Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001, 68 (4): 978-89. 10.1086/319501.CrossRefPubMedPubMedCentral
36.
Ashfield-Watt PA, Welch AA, Day NE, Bingham SA: Is 'five-a-day' an effective way of increasing fruit and vegetable intakes?. Public Health Nutr. 2004, 7: 257-61. 10.1079/PHN2003524.CrossRefPubMed
37.
Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc. 2005, 57: 289-300.
38.
Lewellyn CD, Johnson NW, Warnakulasuriya S: Risk factors for squamous cell carcinoma of the oral cavity in young people: a comprehensive literature review. Oral Oncol. 2001, 37: 401-418. 10.1016/S1368-8375(00)00135-4.CrossRef
39.
Hung RJ, Hel van der O, Tavtigian SV, Brennan P, Boffetta P, Hashibe M: Perspectives on the molecular epidemiology of aerodigestive tract cancers. Mutat Res. 2005, 592 (1–2): 102-18.CrossRefPubMed
40.
Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, Autrup JL, Baranova H, Bathum L, Benhamou S, Boffetta P, et al: Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev. 2001, 10: 1239-1248.PubMed
41.
Rothman KJ, et al: Modern epidemiology. 2008, Lippincott Williams & Wilkins
42.
Mitra S, Sikdar N, Misra C, Gupta S, Paul RR, Roy B, Panda CK, Roychoudhury S: Risk assessment of p53 genotypes and haplotypes in tobacco-associated leukoplakia and oral cancer patients from eastern India. Int J Cancer. 2005, 117 (5): 786-93. 10.1002/ijc.21263.CrossRefPubMed
43.
Buyru N, Altinisik J, Demokan S, Dalay N: p53 genotypes and haplotypes associated with risk of breast cancer. Cancer Detect Prev. 2007, 31 (3): 207-13. 10.1016/j.cdp.2007.04.004.CrossRefPubMed
44.
Ioannidis JPA: Meta-analysis in public health: potential and problems. Ital J Public Health. 2006, 3: 9-14.
45.
Kochethu G, Delgado J, Pepper C, Starczynski J, Hooper L, Krishnan S, Fegan C, Pratt G: Two germ line polymorphisms of the tumour suppressor gene p53 may influence the biology of chronic lymphocytic leukaemia. Leuk Res. 2006, 30 (9): 1113-8. 10.1016/j.leukres.2005.12.014.CrossRefPubMed
46.
De Feo E, Persiani R, LA Greca A, Amore R, Arzani D, Rausei S, D'Ugo D, Magistrelli P, van Duijn CM, Ricciardi G, Boccia S: A case-control study on the effect of p53 and p73 polymorphisms on gastric cancer risk and progression. 2009, Mutat Res: Genet Toxicol Environ Mutagen, 675 (1–2): 60-5. Epub 2009 Mar 3CrossRef
Metadata
Title
A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population
Authors
Paola Gallì
Gabriella Cadoni
Mariangela Volante
Emma De Feo
Rosarita Amore
Arianna Giorgio
Dario Arzani
Gaetano Paludetti
Gualtiero Ricciardi
Stefania Boccia
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-137

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