A genotype-phenotype examination of cyclin D1 on risk and outcome of squamous cell carcinoma of the head and neck

被引:26
作者
Marsit, Carmen J. [1 ]
Black, Candice C. [3 ]
Posner, Marshall R. [4 ]
Kelsey, Karl T. [2 ]
机构
[1] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA
[2] Brown Univ, Ctr Environm Hlth & Technol, Providence, RI 02912 USA
[3] Dartmouth Med Sch, Dept Pathol, Hanover, NH USA
[4] Dana Farber Canc Inst, Dept Med Oncol, Head & Neck Canc Program, Boston, MA 02115 USA
关键词
D O I
10.1158/1078-0432.CCR-07-4368
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: The variant allele of CCND1 G870A encodes a splice variant of the cyclin D1 protein, which possesses an increased half-life. To confirm the phenotypic effect of the variant allele, we examined the immunohistochemical staining pattern of the protein in tumors from a case population of head and neck squamous cell carcinoma (HNSCC) and compared it with the genotype of these individuals. We also examined how this genotype was associated with the risk of HNSCC and if this genotype-phenotype association was related to patient outcome. Experimental Design: In a population-based case-control study of 698 cases and 777 controls, we both genotyped all participants for the CCND1 gene and did immunohistochemical staining of the cyclin D1 protein in the HNSCC tumors. Results: The variant AA genotype was significantly associated with positive immunohistochemical staining (P < 0.02), and this variant genotype was associated with a significantly elevated odds ratio of 1.5 (95% confidence interval, 1.1-2.0) for HNSCC overall, with risk greatest in oral and laryngeal sites. Positive immunohistochemical staining was inversely related to human papillomavirus 16 DNA present in the tumor (P < 0.03). The AA genotype and superpositive immunohistochemical staining for cyclin D1 also had independent and significant effects on patient survival. Conclusions: These results strongly suggest that this splice variant, when present in two copies, is a significant predictor of both the occurrence of HNSCC as well as patient survival after treatment. These data further indicate that this variant protein is an important determinant of individual response to therapy for this disease.
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页码:2371 / 2377
页数:7
相关论文
共 29 条
  • [1] BARTKOVA J, 1995, CANCER RES, V55, P949
  • [2] BETTICHER DC, 1995, ONCOGENE, V11, P1005
  • [3] BLOT WJ, 1988, CANCER RES, V48, P3282
  • [4] Brambilla E, 1999, J PATHOL, V188, P351, DOI 10.1002/(SICI)1096-9896(199908)188:4<351::AID-PATH385>3.0.CO
  • [5] 2-W
  • [6] Clinical implications of human papillomavirus in head and neck cancers
    Fakhry, Carole
    Gillison, Maura L.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (17) : 2606 - 2611
  • [7] Frierson HF, 1996, MODERN PATHOL, V9, P725
  • [8] Human papillomavirus 16 and head and neck squamous cell carcinoma
    Furniss, C. Sloane
    McClean, Michael D.
    Smith, Judith F.
    Bryan, Janine
    Nelson, Heather H.
    Peters, Edwards S.
    Posner, Marshall R.
    Clark, John R.
    Eisen, Ellen A.
    Kelsey, Karl T.
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (11) : 2386 - 2392
  • [9] Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers
    Gillison, ML
    Shah, KV
    [J]. CURRENT OPINION IN ONCOLOGY, 2001, 13 (03) : 183 - 188
  • [10] The hallmarks of cancer
    Hanahan, D
    Weinberg, RA
    [J]. CELL, 2000, 100 (01) : 57 - 70