Top

BMC Cancer

Published in:

Open Access 01-12-2016 | Research article

Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck

Authors: Yan Sun, Wenbin Yu, Erich M. Sturgis, Wei Peng, Dapeng Lei, Qingyi Wei, Xicheng Song, Guojun Li

Published in: BMC Cancer | Issue 1/2016

Abstract

Background

FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).

Method

In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.

Results

The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95 % CI, 1.1–5.8, P = 0.043 and aHR, 2.7; 95 % CI, 1.2–6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95 % CI, 1.2–5.7 and 1.1–3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95 % CI, 1.1–5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.

Conclusion

These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.

Li G, Sturgis EM. The role of human papillomavirus in squamous carcinoma of the head and neck. Curr Oncol Rep. 2006;8(2):130–9.CrossRefPubMed

Sturgis EM, Miller RH. Second primary malignancies in the head and neck cancer patient. Ann Otol Rhinol Laryngol. 1995;104(12):946–54.CrossRefPubMed

Morris LG, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. Journal of Clin Oncol. 2011;29(6):739–46. doi:10.1200/JCO.2010.31.8311.CrossRef

Bosetti C, Scelo G, Chuang SC, Tonita JM, Tamaro S, Jonasson JG, et al. High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries. Int J Cancer. 2011;129(1):173–9. doi:10.1002/ijc.25652.PubMedCentralCrossRefPubMed

Leon X, Quer M, Diez S, Orus C, Lopez-Pousa A, Burgues J. Second neoplasm in patients with head and neck cancer. Head Neck. 1999;21(3):204–10.CrossRefPubMed

Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993;328(3):184–94. doi:10.1056/NEJM199301213280306.CrossRefPubMed

Ernster JA, Sciotto CG, O’Brien MM, Finch JL, Robinson LJ, Willson T, et al. Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus. Laryngoscope. 2007;117(12):2115–28. doi:10.1097/MLG.0b013e31813e5fbb.CrossRefPubMed

Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009;125(2):362–6. doi:10.1002/ijc.24339.CrossRefPubMed

Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, et al. Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 2010;16(4):1226–35. doi:10.1158/1078-0432.CCR-09-2350.PubMedCentralCrossRefPubMed

10.

Rennemo E, Zatterstrom U, Boysen M. Impact of second primary tumors on survival in head and neck cancer: an analysis of 2,063 cases. Laryngoscope. 2008;118(8):1350–6. doi:10.1097/MLG.0b013e318172ef9a.CrossRefPubMed

11.

Yamamoto E, Shibuya H, Yoshimura R, Miura M. Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma. Cancer. 2002;94(7):2007–14.CrossRefPubMed

12.

Zhang Y, Sturgis EM, Zafereo ME, Wei Q, Li G. p14ARF genetic polymorphisms and susceptibility to second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Cancer. 2011;117(6):1227–35. doi:10.1002/cncr.25605.PubMedCentralCrossRefPubMed

13.

Day GL, Blot WJ, Shore RE, McLaughlin JK, Austin DF, Greenberg RS, et al. Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst. 1994;86(2):131–7.CrossRefPubMed

14.

Do KA, Johnson MM, Lee JJ, Wu XF, Dong Q, Hong WK, et al. Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies. Cancer. 2004;101(12):2837–42. doi:10.1002/cncr.20714.CrossRefPubMed

15.

Wu X, Spitz MR, Lee JJ, Lippman SM, Ye Y, Yang H, et al. Novel susceptibility loci for second primary tumors/recurrence in head and neck cancer patients: large-scale evaluation of genetic variants. Cancer Prevention Res. 2009;2(7):617–24. doi:10.1158/1940-6207.CAPR-09-0025.CrossRef

16.

Gal TJ, Huang WY, Chen C, Hayes RB, Schwartz SM. DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients. Laryngoscope. 2005;115(12):2221–31. doi:10.1097/01.mlg.0000183736.96004.f7.CrossRefPubMed

17.

Minard CG, Spitz MR, Wu X, Hong WK, Etzel CJ. Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer. Cancer. 2006;106(12):2636–44. doi:10.1002/cncr.21928.CrossRefPubMed

18.

Li F, Sturgis EM, Zafereo ME, Liu Z, Wang LE, Wei Q, et al. 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. doi:10.1002/ijc.24570.PubMedCentralCrossRefPubMed

19.

Zafereo ME, Sturgis EM, Aleem S, Chaung K, Wei Q, Li G. Glutathione S-transferase polymorphisms and risk of second primary malignancy after index squamous cell carcinoma of the head and neck. Cancer Prevention Res. 2009;2(5):432–9. doi:10.1158/1940-6207.CAPR-08-0222.CrossRef

20.

Zafereo ME, Sturgis EM, Liu Z, Wang LE, Wei Q, Li G. Nucleotide excision repair core gene polymorphisms and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Carcinogenesis. 2009;30(6):997–1002. doi:10.1093/carcin/bgp096.PubMedCentralCrossRefPubMed

21.

Lei D, Sturgis EM, Liu Z, Zafereo ME, Wei Q, Li G. Genetic polymorphisms of p21 and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Carcinogenesis. 2010;31(2):222–7. doi:10.1093/carcin/bgp279.PubMedCentralCrossRefPubMed

22.

Zornig M, Hueber A, Baum W, Evan G. Apoptosis regulators and their role in tumorigenesis. Biochim Biophys Acta. 2001;1551(2):F1–37.PubMed

23.

Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267(5203):1456–62.CrossRefPubMed

24.

Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature. 2001;411(6835):342–8. doi:10.1038/35077213.CrossRefPubMed

25.

Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991;66(2):233–43.CrossRefPubMed

26.

Zhang Z, Wang LE, Sturgis EM, El-Naggar AK, Hong WK, Amos CI, et al. Polymorphisms of FAS and FAS ligand genes involved in the death pathway and risk and progression of squamous cell carcinoma of the head and neck. Clin Cancer Res. 2006;12(18):5596–602. doi:10.1158/1078-0432.CCR-05-1739.CrossRefPubMed

27.

Takahashi T, Tanaka M, Inazawa J, Abe T, Suda T, Nagata S. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994;6(10):1567–74.CrossRefPubMed

28.

Lei D, Sturgis EM, Wang LE, Liu Z, Zafereo ME, Wei Q, et al. FAS and FASLG genetic variants and risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prevention. 2010;19(6):1484–91. doi:10.1158/1055-9965.EPI-10-0030.CrossRef

29.

Warren S, Gates O. Multiple primary malignant tumors a survey of the literature and a statistical study. Am J Cancer. 1932;16:1358–414.

30.

Reichmann E. The biological role of the Fas/FasL system during tumor formation and progression. Semin Cancer Biol. 2002;12(4):309–15.CrossRefPubMed

31.

Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270(5239):1189–92.CrossRefPubMed

32.

Strand S, Hofmann WJ, Hug H, Muller M, Otto G, Strand D, et al. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? Nat Med. 1996;2(12):1361–6.CrossRefPubMed

33.

Muschen M, Warskulat U, Beckmann MW. Defining CD95 as a tumor suppressor gene. J Mol Med. 2000;78(6):312–25.CrossRefPubMed

34.

Zhang X, Miao X, Sun T, Tan W, Qu S, Xiong P, et al. Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer. J Med Genet. 2005;42(6):479–84. doi:10.1136/jmg.2004.030106.PubMedCentralCrossRefPubMed

35.

Zhang B, Sun T, Xue L, Han X, Zhang B, Lu N, et al. Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer. Carcinogenesis. 2007;28(5):1067–73. doi:10.1093/carcin/bgl250.CrossRefPubMed

36.

Sun T, Miao X, Zhang X, Tan W, Xiong P, Lin D. Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma. J Natl Cancer Inst. 2004;96(13):1030–6.CrossRefPubMed

37.

Yang S, Miao XP, Zhang XM, Sun T, Qu SN, Xiong P, et al. Genetic polymorphisms of apoptosis-associated genes FAS and FASL and risk of colorectal cancer. Zhonghua yi xue za zhi. 2005;85(30):2132–5.PubMed

38.

Ueda M, Terai Y, Kanda K, Kanemura M, Takehara M, Yamaguchi H, et al. Fas gene promoter −670 polymorphism in gynecological cancer. International J Gynecol Cancer. 2006;16 Suppl 1:179–82. doi:10.1111/j.1525-1438.2006.00505.x.CrossRef

39.

Li Y, Hao YL, Kang S, Zhou RM, Wang N, Qi BL. Genetic polymorphisms in the Fas and FasL genes are associated with epithelial ovarian cancer risk and clinical outcomes. Gynecol Oncol. 2013;128(3):584–9. doi:10.1016/j.ygyno.2012.12.002.CrossRefPubMed

40.

Lai HC, Lin WY, Lin YW, Chang CC, Yu MH, Chen CC, et al. Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis: An analysis of haplotype and gene-gene interaction. Gynecol Oncol. 2005;99(1):113–8. doi:10.1016/j.ygyno.2005.05.010.CrossRefPubMed

41.

Krippl P, Langsenlehner U, Renner W, Koppel H, Samonigg H. Re: Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma. J Natl Cancer Inst. 2004;96(19):1478–9. doi:10.1093/jnci/djh289. author reply 9.CrossRefPubMed

42.

Sun T, Zhou Y, Li H, Han X, Shi Y, Wang L, et al. FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer. J Exp Med. 2005;202(7):967–74. doi:10.1084/jem.20050707.PubMedCentralCrossRefPubMed

43.

Park JY, Lee WK, Jung DK, Choi JE, Park TI, Lee EB, et al. Polymorphisms in the FAS and FASL genes and survival of early stage non-small cell lung cancer. Clin Cancer Res. 2009;15(5):1794–800. doi:10.1158/1078-0432.CCR-08-1770.CrossRefPubMed

44.

Wang LH, Ting SC, Chen CH, Tsai CC, Lung O, Liu TC, et al. Polymorphisms in the apoptosis-associated genes FAS and FASL and risk of oral cancer and malignant potential of oral premalignant lesions in a Taiwanese population. J Oral Pathology Med. 2010;39(2):155–61. doi:10.1111/j.1600-0714.2009.00873.x.CrossRef

45.

Cao Y, Miao XP, Huang MY, Deng L, Lin DX, Zeng YX, et al. Polymorphisms of death pathway genes FAS and FASL and risk of nasopharyngeal carcinoma. Mol Carcinog. 2010;49(11):944–50. doi:10.1002/mc.20676.CrossRefPubMed

46.

Karimi MY, Kapoor V, Sharma SC, Das SN. Genetic polymorphisms in FAS (CD95) and FAS ligand (CD178) promoters and risk of tobacco-related oral carcinoma: gene-gene interactions in high-risk Indians. Cancer Invest. 2013;31(1):1–6. doi:10.3109/07357907.2012.743555.CrossRefPubMed

47.

Wang J, Gao J, Li Y, Zhao X, Gao W, Peng L, et al. Functional polymorphisms in FAS and FASL contribute to risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population. Gene. 2013;524(2):193–6. doi:10.1016/j.gene.2013.04.034.CrossRefPubMed

48.

Souza RF, Shewmake K, Pearson S, Sarosi Jr GA, Feagins LA, Ramirez RD, et al. Acid increases proliferation via ERK and p38 MAPK-mediated increases in cyclooxygenase-2 in Barrett’s adenocarcinoma cells. Am J Physiol Gastrointest Liver Physiol. 2004;287(4):G743–8. doi:10.1152/ajpgi.00144.2004.CrossRefPubMed

49.

Yang M, Sun T, Wang L, Yu D, Zhang X, Miao X, et al. Functional variants in cell death pathway genes and risk of pancreatic cancer. Clin Cancer Res. 2008;14(10):3230–6. doi:10.1158/1078-0432.CCR-08-0177.CrossRefPubMed

Title: Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck
Authors: Yan Sun
Wenbin Yu
Erich M. Sturgis
Wei Peng
Dapeng Lei
Qingyi Wei
Xicheng Song
Guojun Li
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2110-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2016

Poor survival in stage IIB/C (T4N0) compared to stage IIIA (T1-2 N1, T1N2a) colon cancer persists even after adjusting for adequate lymph nodes retrieved and receipt of adjuvant chemotherapy

Tissue metabolic profiling of human gastric cancer assessed by 1H NMR

A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer

Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2

High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes

A case of lymphangioleiomyomatosis associated with endometrial cancer and severe systemic lupus erythematosus

Keynote webinar | Spotlight on antibody–drug conjugates in cancer