Cyclin D1 gene G870A polymorphism predicts response to neoadjuvant radiotherapy and prognosis in rectal cancer.
OBJECTIVE
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
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.
Ho-Pun-Cheung
Alexandre
A
INSERM U860, and Department of Oncobiology, Val d'Aurelle Cancer Institute, 208 rue des Apothicaires, 34298 Montpellier, France.
Assenat
Eric
E
Thezenas
Simon
S
Bibeau
Frédéric
F
Rouanet
Philippe
P
Azria
David
D
Cellier
Dominic
D
Grenier
Jean
J
Ychou
Marc
M
Senesse
Pierre
P
Lopez-Crapez
Evelyne
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019940:Genes, bcl-1 / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011110:Polymorphism, Genetic; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery
D005819:Genetic Markers; D019938:Cyclin D1