Cyclin D1 Gene G870A Polymorphism Predicts Response to Neoadjuvant Radiotherapy and Prognosis in Rectal Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 68; no. 4; pp. 1094 - 1101
• Main Authors: Ho-Pun-Cheung, Alexandre, M.S, Assenat, Eric, M.D, Thezenas, Simon, M.S, Bibeau, Frédéric, M.D, Rouanet, Philippe, M.D., Ph.D, Azria, David, M.D., Ph.D, Cellier, Dominic, M.D, Grenier, Jean, Ph.D, Ychou, Marc, M.D., Ph.D, Senesse, Pierre, M.D., Ph.D, Lopez-Crapez, Evelyne, Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2007; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Biochemistry, Molecular Biology; Cancer; CARCINOMAS; Cyclin D1; Cyclin D1 - genetics; DNA Mutational Analysis; Female; GENES; Genes, bcl-1 - genetics; Genetic Markers; Genomics; Genotype; Hematology, Oncology and Palliative Medicine; Humans; Life Sciences; LYMPH NODES; Male; Middle Aged; MUTATIONS; Neoadjuvant Therapy - methods; Neoplasm Recurrence, Local - genetics; NUCLEOTIDES; PATIENTS; Polymorphism, Genetic; Predictive marker; Prognosis; PROTEINS; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOSENSITIVITY; RADIOTHERAPY; Rectal cancer; Rectal Neoplasms - genetics; Rectal Neoplasms - radiotherapy; Rectal Neoplasms - surgery; RECTUM; Single nucleotide polymorphism; Single nucleotide polymorphism; Rectal cancer; Cyclin D1; Radiotherapy; Predictive marker
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2007.01.022

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.