BAX UTR G (-248) A Polymorphism Has No Impact on Survival in Patients with Multiple Myeloma.

Multiple myeloma is a malignant tumour of plasma cells that remains incurable for the vast majority of patients with a median survival of 2–3 years. The bax protein is a member of the Bcl-2 family and is an important pro-apoptotic protein. Low BAX expression has been shown to be associated with prolonged survival in patients with myeloma(1). A novel polymorphism, G(-248)A in the BAX promoter in patients with Chronic lymphocytic leukaemia (CLL) has shown to be associated with reduced Bax protein expression, progressive disease and treatment failure(2, 3). We report here the impact of this polymorphism on survival in 304 (M: 168; F: 136) patients with myeloma

Materials and Methods

This study included 158 (M: 89; F: 69) patients from MRC Myeloma VII trial and 146 (M: 79; F: 67) under our care from January 1992 and February 2006. DNA was extracted from myeloma patients and healthy volunteer’s peripheral blood using a standard salting out method. Analysis of the 5-UTR polymorphism was undertaken using method already published by our centre(3). Patients received either intensive or non intensive antimyeloma therapy as per standard practice. Statistical analysis was carried out using SAS software.

Results

The frequency of GG and GA/AA genotypes was 81.6% and 18.4% in myeloma patients as compared to 85.2% and 14.8% in normal controls. Median age at diagnosis was 58 yr (range 34–87 yrs). (GA/AA Group: 58 yrs (42–85); GG Group: 58 yr (34–87)). There were no significant differences in the sex distribution, β2 microglobulin, haemoglobin, bone lesions, calcium and age between the GA/AA & GG groups with p values 0.72, 0.46, 0.95, 0.61, 0.49 and 0.46 respectively. Abnormal creatinine levels were significantly few in GA/AA group (p value: 0.002). Median survival for the AA/GA group was 48 months (95% CI 36 – 61 months) compared with 54 months in the GG group (95% CI 46 – 63 months)[p=0.5 log-rank test] with a median follow up of 62 months (range 1 to 141).

Conclusions

Our results show that the GA/AA polymorphism has no impact on the overall survival in patients with myeloma. Further work is ongoing in order to assess the impact of this polymorphism on response in various treatment groups.