Neither the putative risk genotypes ADH1B*2/*1 (OR 0.86, 95% confidence interval (CI): 0.41-1.82) or ADH1C*1/*1 (OR 1.06, CI 0.7-1.62) nor GSTM1 null (OR 0.94, CI 0.62-1.42) or GSTT1 null (OR 1.34, CI 0.74-2.42) were associated with an overall increased risk for laryngeal cancer.
TP53 mutations were found in 22 of 58 (37.9%) patients with advanced larynx cancer, including missense mutations in 13 of 58 (22.4%) patients, nonsense mutations in four of 58 (6.9%), and deletions in five of 58 (8.6%).
In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism is an increased risk of laryngeal cancer in Asians and Caucasians.
Subgroup analyses by ethnicity showed that the GSTM1 null genotype was associated with increased laryngeal cancer risk in both Caucasians (fixed-effects OR = 1.17, 95 % CI 1.04-1.33, P = 0.012) and Asians (random-effects OR = 1.89, 95 % CI 1.28-2.77, P = 0.001).
The combined results based on all studies showed that GSTM1 null genotype was associated with increased laryngeal cancer risk (OR = 1.17, 95% CI = 1.04∼1.31).
The results suggest that the GSTM1 deficiency significantly increases susceptibility to laryngeal cancer whereas GSTT1 null genotype might not be a risk factor.
However, we did not find a significant increase in laryngeal cancer risk for the homozygous Pro/Pro TP53 genotype OR=2.093 (95% CI=1.046-4.192, P=0.0530).
Furthermore, the TP53 mutational hot spots for lung and laryngeal cancers from smokers included codons 157, 245 and 273, whereas for oral tumors included codons 280 and 281.
In papillomatosis, pRb and p53 levels were higher than in normal larynxes, whereas laryngeal cancer presented the lowest levels. c-Myc oncogene expression was very low in normal and cancer tissues but highly increased in papillomatosis.
Flow cytometric Annexin V assay demonstrated that HEp-2 cells (human laryngeal cancer) were persistently resistant to CDDP as compared to HeLa cells (human uterine cervical cancer), despite the same histological type and wild-type p53 status.
We screened exons 5-8 of TP53 for mutations in DNA from tumor biopsies (n = 44) and blood samples (n = 42) from the same LC patients, and blood samples from a healthy, matched control group (n = 40), using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing.
Neither the putative risk genotypes ADH1B*2/*1 (OR 0.86, 95% confidence interval (CI): 0.41-1.82) or ADH1C*1/*1 (OR 1.06, CI 0.7-1.62) nor GSTM1 null (OR 0.94, CI 0.62-1.42) or GSTT1 null (OR 1.34, CI 0.74-2.42) were associated with an overall increased risk for laryngeal cancer.
We showed that the risk of developing laryngeal cancer was increased by 2.6-fold [95% CI 1.6--6.1] in patients with the GSTM1 null genotype and by 2.8-fold [95% CI 0.9--8.1] in patients with the homozygous GSTP1 val105 genotype.
The results suggest that the co-transfer of human wild-type p53 and GM-CSF genes into tumor cells via recombinant adenovirus may be further developed into an effective and practical combination gene therapy strategy for laryngeal cancer.