ABSTRACT
Genetic variants in glioma tumor suppressor candidate region gene 1 (GLTSCR1)and ATM serine/threonine kinase (ATM) have been associated with various cancer risks.Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors.However,little is known about the relationship between both gene polymorphisms and lung cancer risk.We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls.No significant differences in the single polymorphism (GLTSCR1 rs1035938 and ATM rs11212592)association were found in five genetic models (co-dominant,dominant,recessive,overdominant and log-additive models) (adjusted by smoking duration).Join effect of three SNPs (PPP1R13L rs1970764,CD3EAP rs967591,GLTSCR1 rs1035938) on chromosome 19q 13.3 showed that the designated haplotype2 (rs 1970764<rs967591A-rs 1035938c) [OR (95％ CI)=1.60 (1.11-2.32),P=0.012] and haplotype8 (rs 1970764G-rs967591G-rs 1035938T)[OR (95％ CI)=2.45 (1.17-5.12),P=0.018] were associated with increased risk of lung cancer (adjusted by smoking duration).The analysis ofmultifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci (P＜0.001)or 4 loci (P=0.015-0.016).The entropy-based analysis indicated the strongest synergistic effect between PPP1R13L rs1970764 and ATM rs11212592 in analysis of four genes.In conclusion,our study suggests that haplotypes consisting of PPP1R13L rs1970764-CD3EAP rs967591-GLTSCR1 rs1035938 on Chr19q13.3,interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592,and synergistic action of PPP1R13L rs1970764 and ATMrs11212592 may associate with lung cancer risk in the Chinese population.
ABSTRACT
Genetic variants in glioma tumor suppressor candidate region gene 1 (GLTSCR1)and ATM serine/threonine kinase (ATM) have been associated with various cancer risks.Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors.However,little is known about the relationship between both gene polymorphisms and lung cancer risk.We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls.No significant differences in the single polymorphism (GLTSCR1 rs1035938 and ATM rs11212592)association were found in five genetic models (co-dominant,dominant,recessive,overdominant and log-additive models) (adjusted by smoking duration).Join effect of three SNPs (PPP1R13L rs1970764,CD3EAP rs967591,GLTSCR1 rs1035938) on chromosome 19q 13.3 showed that the designated haplotype2 (rs 1970764<rs967591A-rs 1035938c) [OR (95％ CI)=1.60 (1.11-2.32),P=0.012] and haplotype8 (rs 1970764G-rs967591G-rs 1035938T)[OR (95％ CI)=2.45 (1.17-5.12),P=0.018] were associated with increased risk of lung cancer (adjusted by smoking duration).The analysis ofmultifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci (P＜0.001)or 4 loci (P=0.015-0.016).The entropy-based analysis indicated the strongest synergistic effect between PPP1R13L rs1970764 and ATM rs11212592 in analysis of four genes.In conclusion,our study suggests that haplotypes consisting of PPP1R13L rs1970764-CD3EAP rs967591-GLTSCR1 rs1035938 on Chr19q13.3,interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592,and synergistic action of PPP1R13L rs1970764 and ATMrs11212592 may associate with lung cancer risk in the Chinese population.