Polymorphisms in tumour necrosis factor (TNF) are associated with risk of bladder cancer and grade of tumour at presentation

Abstract

The purpose of this study is to assess the role of tumour necrosis factor (TNF) polymorphisms in the risk of developing bladder cancer and effect on tumour stage, grade and progression. In all, seven single-nucleotide polymorphisms in TNF were studied in 196 bladder cancer patients and 208 controls using a PCR-SSP genotyping technique. It was seen that there was a significant association of two polymorphisms in TNF with bladder cancer: the TNF þ 488A allele was found in 28.1% of patients compared with 14.9% of controls (P ¼ 0.0012). In addition, TNFÀ859T was found in 26.0% of patients compared with 14.4% of the controls (P ¼ 0.0036). The two loci were in tight linkage disequilibrium, that is, almost all the individuals having TNF þ 488A also had TNFÀ859T. Patients with the TNF þ 488A or TNFÀ859T were more likely to present with a moderately differentiated tumour than those patients without the uncommon allele. In all, 16.7% of patients with TNF þ 488A and 29.9% of patients without TNF þ 488A presented with a G1 tumour (P ¼ 0.015). A total of 14% of patients with TNFÀ859T and 30.5% of patients without TNFÀ859T presented with a G1 tumour (P ¼ 0.0043). There was no significant effect on time to first recurrence, stage progression or grade progression. In conclusion, a significant association between TNF polymorphisms TNF þ 488A and TNFÀ859T and risk of bladder cancer was detected in this study. Both these polymorphisms were associated with grade of tumour at presentation although there was no significant effect on subsequent tumour behaviour.

Genetic susceptibility to tobacco-related cancer

“…In bladder cancer, Inatomi et al (1999) showed that bladder cancer patients with NAT2 slow genotypes were more likely to have a high-grade tumor (G3) or an advanced stage tumor (pT2-pT4). Also, significant associations between TNF polymorphisms TNF þ 488A and TNFÀ859T and grade of bladder cancer were observed (Marsh et al, 2003).…”

Tumor Necrosis Factor-α Gene Polymorphisms and Risk of Oral Cancer: Evidence from a Meta-analysis

“…Commonly described variants of TNF-α gene polymorphisms consist of G to A transitions in the promoter region at positions _238 and _308 (Kaluza et al, 2000). So far, TNF-α promoter polymorphism has been related to numerous cancers, such as bladder cancer (Marsh et al, 2003), renal cell carcinoma (Nakajima et al, 2001), non-small cell lung carcinoma (Shih et al, 2006) cervical cancer (Govan et al, 2006;Liu et al, 2012b) and breast carcinoma (Mestiri et al, 2001).…”

IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development

“…Bladder cancer patients carrying the A allele seem to have increased TNF-␣ in serum and tumor tissue [43] . Although the TNF-308G/A polymorphism was described as being associated with grade, much debate still exists concerning its association with stage and other clinicopathological characteristics [43,44] .…”