Genetic Variants in P53-related Genes Confer Susceptibility to Second Primary Malignancy in Patients with Index Squamous Cell Carcinoma of Head and Neck

Overview

Journal Carcinogenesis

Specialty Oncology

Date 2013 Mar 20

PMID 23508638

Citations 9

Authors

Lei Jin

Erich M Sturgis

Yang Zhang

Zhigang Huang

Peng Wei

Wei Guo

Zhongqiu Wang

Qingyi Wei

Xicheng Song

Guojun Li

Affiliations

Soon will be listed here.

Abstract

Because of their important roles in mediating the stabilization and expression of p53, we hypothesized that high-risk genotypes of polymorphisms in p53-related genes, including p53, p73, p14(ARF), MDM2 and MDM4, may be associated with an increased risk of second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). We analyzed data from a cohort of 1283 patients with index SCCHN who were recruited between 1995 and 2007 at MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for nine polymorphisms of p53-related genes. A log-rank test and Cox models were used to compare SPM-free survival and risk. Our results demonstrated that each p53-related polymorphism had a moderate effect on increased SPM risk, but when we combined risk genotypes of these nine polymorphisms together, we found that SPM-free survival was significantly shorter among risk groups with a greater number of combined risk genotypes. SPM risk increased with increasing number of risk genotypes (P < 0.0001 for trend). Compared with the low-risk group (0-3 combined risk genotypes), both the medium-risk (4-5 combined risk genotypes) and high-risk (6-9 combined risk genotypes) groups had significantly increased SPM risk [hazard ratio (HR): 1.6; 95% confidence interval (CI): 1.0-2.6 and HR: 3.0; 95% CI: 1.8-5.0, respectively]. Moreover, such significant associations were even higher in several subgroups. Our findings suggest that combined risk genotypes of p53-related genes may jointly modify SPM risk, especially in patients who are smokers and those with index non-oropharyngeal cancers. However, larger studies are needed to validate our findings.

Citing Articles

Genomic alterations in oral multiple primary cancers.

Zhou X, Cai X, Jing F, Li X, Zhang J, Zhang H Int J Oral Sci. 2024; 16(1):13.

PMID: 38368361 PMC: 10874441. DOI: 10.1038/s41368-023-00265-w.

Single nucleotide polymorphisms and the risk of developing a second primary cancer among head and neck cancer patients: a systematic literature review and meta-analysis.

Hoxhaj I, Vukovic V, Boccia S, Pastorino R BMC Cancer. 2021; 21(1):660.

PMID: 34078296 PMC: 8173958. DOI: 10.1186/s12885-021-08335-0.

Susceptibility of Multiple Primary Cancers in Patients With Head and Neck Cancer: Nature or Nurture?.

Zhang W, Zhu Z, Huang M, Tang Y, Tang Y, Liang X Front Oncol. 2019; 9:1275.

PMID: 31824853 PMC: 6882292. DOI: 10.3389/fonc.2019.01275.

A genetic variant within MDM4 3'UTR miRNA binding site is associated with HPV16-positive tumors and survival of oropharyngeal cancer.

Zhang Y, Sturgis E, Wei P, Liu H, Wang Z, Ma Y Mol Carcinog. 2019; 58(12):2276-2285.

PMID: 31513313 PMC: 6874914. DOI: 10.1002/mc.23116.

A Case-Control Study of Risk Factors for Salivary Gland Cancer in Canada.

Pan S, de Groh M, Morrison H J Cancer Epidemiol. 2017; 2017:4909214.

PMID: 28133481 PMC: 5241483. DOI: 10.1155/2017/4909214.

References

Wang L, Gao R, Yu L . Combined analysis of the association between p73 G4C14-to-A4T14 polymorphisms and cancer risk. Mol Biol Rep. 2011; 39(2):1731-8. DOI: 10.1007/s11033-011-0913-0. View

Liu F, Liu L, Li B, Wei Y, Yan L, Wen T . p73 G4C14-A4T14 polymorphism and cancer risk: a meta-analysis based on 27 case-control studies. Mutagenesis. 2011; 26(4):573-81. DOI: 10.1093/mutage/ger018. View

Pfeifer G, Denissenko M, Olivier M, Tretyakova N, Hecht S, Hainaut P . Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene. 2002; 21(48):7435-51. DOI: 10.1038/sj.onc.1205803. View

Wu X, Spitz M, Lee J, Lippman S, Ye Y, Yang H . Novel susceptibility loci for second primary tumors/recurrence in head and neck cancer patients: large-scale evaluation of genetic variants. Cancer Prev Res (Phila). 2009; 2(7):617-24. PMC: 2964280. DOI: 10.1158/1940-6207.CAPR-09-0025. View

Leemans C, Braakhuis B, Brakenhoff R . The molecular biology of head and neck cancer. Nat Rev Cancer. 2010; 11(1):9-22. DOI: 10.1038/nrc2982. View

Sturgis E, Miller R . Second primary malignancies in the head and neck cancer patient. Ann Otol Rhinol Laryngol. 1995; 104(12):946-54. DOI: 10.1177/000348949510401206. View

Harris S, Levine A . The p53 pathway: positive and negative feedback loops. Oncogene. 2005; 24(17):2899-908. DOI: 10.1038/sj.onc.1208615. View

Xia L, Paik A, Li J . p53 activation in chronic radiation-treated breast cancer cells: regulation of MDM2/p14ARF. Cancer Res. 2004; 64(1):221-8. DOI: 10.1158/0008-5472.can-03-0969. View

Zhang Y, Sturgis E, Huang Z, Zafereo M, Wei Q, Li G . Genetic variants of the p53 and p73 genes jointly increase risk of second primary malignancies in patients after index squamous cell carcinoma of the head and neck. Cancer. 2011; 118(2):485-92. PMC: 3184342. DOI: 10.1002/cncr.26222. View

10.

SLAUGHTER D, SOUTHWICK H, SMEJKAL W . Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953; 6(5):963-8. DOI: 10.1002/1097-0142(195309)6:5<963::aid-cncr2820060515>3.0.co;2-q. View

11.

Almadori G, Bussu F, Cadoni G, Galli J, Rigante M, Artuso A . Multistep laryngeal carcinogenesis helps our understanding of the field cancerisation phenomenon: a review. Eur J Cancer. 2004; 40(16):2383-8. DOI: 10.1016/j.ejca.2004.04.023. View

12.

Muto M, Nakane M, Hitomi Y, Yoshida S, Sasaki S, Ohtsu A . Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer. Carcinogenesis. 2002; 23(10):1759-65. DOI: 10.1093/carcin/23.10.1759. View

13.

Morris L, Sikora A, Hayes R, Patel S, Ganly I . Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. Cancer Causes Control. 2011; 22(5):671-9. PMC: 3085084. DOI: 10.1007/s10552-011-9739-2. View

14.

Yu H, Huang Y, Liu Z, Wang L, Li G, Sturgis E . Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog. 2011; 50(9):697-706. PMC: 3142329. DOI: 10.1002/mc.20806. View

15.

Li F, Sturgis E, Zafereo M, Liu Z, Wang L, Wei Q . p73 G4C14-to-A4T14 polymorphism and risk of second primary malignancy after index squamous cell carcinoma of head and neck. Int J Cancer. 2009; 125(11):2660-5. PMC: 2757513. DOI: 10.1002/ijc.24570. View

16.

Manikantan K, Dwivedi R, Sayed S, Pathak K, Kazi R . Current concepts of surveillance and its significance in head and neck cancer. Ann R Coll Surg Engl. 2011; 93(8):576-82. PMC: 3566680. DOI: 10.1308/003588411X604794. View

17.

Leon X, Venegas M, Orus C, Lopez M, Garcia J, Quer M . Influence of the persistence of tobacco and alcohol use in the appearance of second neoplasm in patients with a head and neck cancer. A case-control study. Cancer Causes Control. 2008; 20(5):645-52. DOI: 10.1007/s10552-008-9277-8. View

18.

Weber A, Bellmann U, Bootz F, Wittekind C, Tannapfel A . INK4a-ARF alterations and p53 mutations in primary and consecutive squamous cell carcinoma of the head and neck. Virchows Arch. 2002; 441(2):133-42. DOI: 10.1007/s00428-002-0637-6. View

19.

Sun T, Lee G, Oh W, Pomerantz M, Yang M, Xie W . Single-nucleotide polymorphisms in p53 pathway and aggressiveness of prostate cancer in a Caucasian population. Clin Cancer Res. 2010; 16(21):5244-51. PMC: 2970725. DOI: 10.1158/1078-0432.CCR-10-1261. View

20.

Dahlstrom K, Little J, Zafereo M, Lung M, Wei Q, Sturgis E . Squamous cell carcinoma of the head and neck in never smoker-never drinkers: a descriptive epidemiologic study. Head Neck. 2007; 30(1):75-84. DOI: 10.1002/hed.20664. View