Meta-Analysis Suggests Association of L- myc Eco RI Polymorphism with Cancer Prognosis

Abstract

In patients with other cancers, the S/S genotype was significantly associated with tumor recurrence (OR, 2.8; 95% CI, 1.4 -6.0), whereas no significant association was seen for the other prognostic parameters. When all types of cancer were examined together, the S/S genotype was associated with lymph node metastasis (OR, 2.3; 95% CI, 1.6 -3.3), distant metastasis (OR, 2.9; 95% CI, 1.8 -4.6), clinical stage (OR, 1.8; 95% CI, 1.2-2.9), and cancer risk (OR, 1.25; 95% CI, 1.07-1.45). The meta-analysis suggests that the L-myc EcoRI polymorphism is a marker of tumor prognosis in lung cancer and possibly in other types of cancer.

Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients’ survival

“…Our recent meta-analysis revealed a significant association between the intronic MYCL1-EcoRI variant and lymph node metastasis, distant metastasis, and clinical stage of lung cancer patients [6], supporting the hypothesis that genetic variation in either MYCL1 or a flanking gene determines lung tumour progression. MYCL1 is frequently amplified and overexpressed in small-cell lung cancer but not in a broad range of lung tumour histotypes [7], and no coding polymorphism in this gene was found to be associated with lung tumour prognosis or prognostic factors [8].…”

“…HPLC and mass spectrometry analysis of tRNAs extracted from control and transformed yeast strains revealed no significant differences between the two alleles. Indeed, both variants were functionally active and produced similar amounts of i 6 A (1.43 ± 0.41 and 1.46 ± 0.36 pmol/g tRNA for the Phe and Leu allele, respectively), which were comparable to i 6 A levels measured in the wild-type H57 yeast strain (1.81 ± 0.40 pmol/g tRNA).…”

“…Although contrasting results have been described on the effects of this SNP, a meta-analysis pointed to its significant role in the modulation of cancer prognostic parameters, in particular lymph node status and clinical stage of lung cancer patients [6]. This finding is most likely explained by LD of this SNP with a nearby functional polymorphism that affects lung cancer progression.…”

“…TRIT1 encodes tRNA isopentenyltransferase, which catalyzes the formation of the modified base N 6 -isopentenyladenosine (i 6 A) in position 37 of tRNA molecules that bind codons starting with uridine [11,12]. TRIT1 alleles were tested for functional activity in the yeast strain MT-8, which has defective tRNA-isopentenyltransferase activity and synthesizes tRNAs lacking the isopentenyl-adenosine (i 6 A) modification, as compared with yeast strain H57, which produces an active tRNA-isopentenyltransferase gene.…”

“…TRIT1 alleles were tested for functional activity in the yeast strain MT-8, which has defective tRNA-isopentenyltransferase activity and synthesizes tRNAs lacking the isopentenyl-adenosine (i 6 A) modification, as compared with yeast strain H57, which produces an active tRNA-isopentenyltransferase gene. Yeast transformation and i 6 A analysis were carried out as described [12]. The TRIT1 Phe202 allele was obtained by amplification of a cDNA pool of normal lung tissue with primers 5 -caacggaccctacctcttgt-3 and 5 -cacctttccaaaggccact-3 and cloned into the yeast expression vector pYES2.1/V5-His-TOPO (Invitrogen).…”