title: Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients' survival.
abstract: Linkage disequilibrium (LD) analysis to refine a region associated with lung cancer progression on chromosome 1p34 identified a 106 kb LD block that includes MYCL1, TRIT1 (tRNA isopentenyltransferase 1) and MFSD2 (major facilitator superfamily domain-containing 2). Case-only association study on SNPs mapping in TRIT1 and MFSD2 indicated that the rare Leu allele (frequency: 0.04) of the TRIT1 Phe202Leu variation predicts short survival as compared to the common Phe/Phe genotype (hazard ratio (HR)=1.7; 95% CI, 1.03-2.86; P=0.039) in 335 Italian lung adenocarcinoma samples. A replication study in an independent population of 246 Norwegian lung cancer patients confirmed the significant association of the Phe202Leu polymorphism with patients' survival, but the rare allele was associated with better survival rate (HR=0.5; 95% CI, 0.26-0.91; P=0.023). The rare allele of TRIT1 Phe202Leu SNP was approximately seven-fold more frequent in Asian than in Caucasian subjects and three additional SNPs in the TRIT1 and MFSD2 genes showed ethnic differences in allelic frequencies. These results suggest that polymorphisms in the MYCL1 LD region affect lung cancer survival but that the functional element(s) may show population-specific patterns.
authors.affiliation: Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Spinola
authors.forename: F Stefania
authors.initials: FS
authors.lastname: Falvella
authors.forename: Antonella
authors.initials: A
authors.lastname: Galvan
authors.forename: Carmen
authors.initials: C
authors.lastname: Pignatiello
authors.forename: Vera P
authors.initials: VP
authors.lastname: Leoni
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Rita
authors.initials: R
authors.lastname: Paroni
authors.forename: Shuqing
authors.initials: S
authors.lastname: Chen
authors.forename: Vidar
authors.initials: V
authors.lastname: Skaug
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
mesh_terms: D000230:Adenocarcinoma / Q000208:ethnology* / Q000235:genetics / Q000401:mortality; D019883:Alkyl and Aryl Transferases / Q000235:genetics; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics / Q000401:mortality; D002681:China; D002878:Chromosomes, Human, Pair 1; D016259:Genes, myc; D005838:Genotype; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000208:ethnology* / Q000235:genetics / Q000401:mortality; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D044465:White People / Q000235:genetics
chemical_list: D019883:Alkyl and Aryl Transferases; C023197:tRNA isopentenyltransferase