Cyclin D1 (CCND1) genotype is associated with tumour grade in sporadic pituitary adenomas

Abstract

The cyclin D1 (CCND1) gene contains a frequent A/G polymorphism within the splice donor region of exon 4/intron 4. CCND1 genotype is associated with clinical outcome in a number of malignancies although prognostic significance varies with tumour type. We examined CCND1 allele frequencies and genotype distribution in 294 patients with sporadic pituitary adenomas of various histologies. CCND1 allele frequencies and distribution of genotypes were similar in the 294 cases compared with previously reported control populations. Analysis according to tumour subtype showed no statistical difference in allele frequencies compared with controls. However, CCND1 genotype distribution in the somatotrophinomas showed a significant difference compared with normal controls (P = 0.008). We next examined CCND1 allele frequencies and genotype distribution across the tumour grades. Within the total tumour cohort the CCND1 allele frequencies showed a significant inverse relationship across the tumour grades (P = 0.005). The CCND1 A allele progressively increased from grade 1 (0.37) through to grade 4 (0.62) tumours, whilst the CCND1 G allele frequency progressively decreased from grade 1 (0.63) through to grade 4 (0.38) tumours. Trend analysis of CCND1 genotypes showed a significant progressive increase in AA frequency from grade 1 (15%) through to grade 4 (46%) tumours (P = 0.005). The CCND1 GG genotype progressively decreased from grade 1 (41%) through to grade 4 (23%) tumours (P = 0.204). No statistical significance was observed between CCND1 AG genotype and tumour grades. While the functional significance of the observed segregation of the CCND1 A/G polymorphism and tumour grade is unclear, our data suggest that CCND1 allele frequencies and genotype distributions show significant differences between tumour grades in sporadic pituitary adenomas. Since CCND1 genotype may be determined by analysis of peripheral blood samples it may provide a useful predictive marker for those tumours likely to show invasive behaviour. This may be clinically useful in indicating which tumours should receive adjunctive treatment (e.g. radiotherapy) immediately after surgical resection.

Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism

“…31 In sporadic pituitary adenoma, the AA genotype was associated with high-grade tumors. 17 Our previous study also suggested that the AA genotype was associated with an increased risk of urinary bladder cancer and its progression. 14 The present findings on PCa were consistent with those of previous studies, in which the A allele was implicated in the susceptibility for cancer.…”

Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: A single-center study

“…In addition, the patients were assigned into groups according to invasive or non-invasive tumor behavior. Extrasellar diffusion of adenomas was assessed using the Hardy classification in conjunction with the cavernous sinus invasion (21), and the presence of the latter was ascertained by detailed coronal sellar MRI. Involvement of ≥2/3 (67%) of the internal carotid artery at the cavernous sinus segment was defined as cavernous sinus invasion (22).…”

Cyclin D1: polymorphism, aberrant splicing and cancer risk

“…Of the polymorphisms identified, the cyclin D1 G/A870 polymorphism has received the most investigation. The polymorphism frequency in the Caucasion population is approximately 44% A and 56% G, depending on the study (Simpson et al, 2001;Sanyal et al, 2004), but large variances between racial and ethnic groups have been reported. Owing to the significance of cyclin D1 in human cancer, a large number of epidemiological studies have challenged the influence of this particular polymorphism in cancer susceptibility and disease outcome.…”