Cyclin D1 gene G870A polymorphism predicts response to neoadjuvant radiotherapy and prognosis in rectal cancer

Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):1094-101. doi: 10.1016/j.ijrobp.2007.01.022. Epub 2007 Mar 29.

Abstract

Purpose: To investigate whether CCND1 genetic variations associated with a constitutive nuclear protein may influence either the pathologic response to preoperative RT or the prognosis in a series of rectal cancer patients.

Methods and materials: Seventy rectal cancer patients treated by neoadjuvant radiotherapy were included in the study. CCND1 exon 5 mutations were screened, and the G870A polymorphism was assessed for correlation with clinical variables, tumor response, and patient outcome.

Results: No exon 5 mutation was found. Concerning the G870A polymorphism, the A/A variant was significantly associated with radiosensitivity (p = 0.022). Moreover, patients harboring the A allele were correlated with a lower risk of local failure (p = 0.017). Also, combination of the G870A polymorphism with the post-therapeutic lymph node status allowed the elaboration of a prognostic index, which accurately distinguished subgroups of patients with predictable recurrence-free (p = 0.003) and overall (p = 0.044) survival.

Conclusions: Although CCND1 exon 5 mutations are rare in rectal cancer, G870A polymorphism is a frequent variation that may predict radiosensitivity and prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclin D1 / genetics*
  • DNA Mutational Analysis
  • Female
  • Genes, bcl-1 / genetics*
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Recurrence, Local / genetics
  • Polymorphism, Genetic*
  • Prognosis
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery

Substances

  • Genetic Markers
  • Cyclin D1