Renal Cell Carcinoma Fuhrman Grade and Histological Subtype Correlate With Complete Polymorphic Deletion of Glutathione S-Transferase M1 Gene

Purpose

We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression.

Materials and Methods

Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival.

Results

Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean ± SD age 58.5 ± 14.2 vs 65.4 ± 12.8 years, p = 0.016).

Conclusions

GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Key Words: kidney, carcinoma, renal cell, glutathione transferase, polymorphism, genetic, gene deletion

Abbreviations and Acronyms: ASK1, apoptosis signal-regulating kinase 1, GST, glutathione S-transferase, PCR, polymerase chain reaction, RCC, renal cell carcinoma