p73 G4C14-to-A4T14 polymorphism and risk of second primary malignancy after index squamous cell carcinoma of head and neck.

Full Abstract

P73 plays an important role in modulating cell-cycle control, inducing apoptosis, and inhibiting cell growth. A novel noncoding p73 G4C14-to-A4T14 exon 2 polymorphism was associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that p73 G4C14-to-A4T14 polymorphism modulates risk of second primary malignancies (SPM) in patients after index SCCHN. We followed a cohort of 1,384 patients diagnosed with incident SCCHN between May 1995 and January 2007 for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups. Our results showed that patients carrying the p73 variant AT allele were less likely to develop SPM compared with the patients with p73 GC/GC genotype (Log-rank test, p = 0.013). Compared with the p73 GC/GC genotype, there was a significantly reduced risk of SPM associated with the p73 GC/AT genotype (HR, 0.61, 95% CI, 0.40-0.93) and the combined p73 GC/AT+AT/AT genotypes (HR, 0.59, 95% CI, 0.39-0.89), but a nonsignificantly reduced risk for p73 AT/AT genotype (HR, 0.44, 95% CI, 0.14-1.41). The p73 AT allele was significantly associated with risk of SPM in an allele dose-response manner (p = 0.011 for trend). The risk of SPM associated with p73 variant genotypes (GC/AT+AT/AT) was more pronounced in several subgroups (e.g., older patients, men, minorities, ever smokers, and ever drinkers). Our results support that this p73 polymorphism may be a marker for risk of SPM among patients with an incident SCCHN.

Author information

Author/s: Li, Fanglin (F); Sturgis, Erich M (EM); Zafereo, Mark E (ME); Liu, Zhensheng (Z); Wang, Li-E (LE); Wei, Qingyi (Q); Li, Guojun (G);

Affiliation: Department of Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.

Grants: CA133099 (Agency:NCI NIH HHS) ; CA135679 (Agency:NCI NIH HHS) ; K-12 88084 (Agency:PHS HHS) ; P-30 CA-16672 (Agency:NCI NIH HHS) ; R01 ES-11740 (Agency:NIEHS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Dec; vol 125 (issue 11) : pp 2660-5

Dates: Created 2009/10/05; Completed 2009/11/06;

PMID: 19585505, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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