|
ObjectiveNasopharyngeal carcinoma(NPC) is one of Head and Neck malignancies and occurs at a higher incidence in Southwest China.NPC has a strong genetic predisposition, racial distribution and familial aggregation.The aim of this study was to investigate the susceptibility and prognostic implications of the CCND1 G870A and MMP-1(-1607)1G/2G polymorphisms to NPC in Han population in Yunnan China.MethodsTwo hundred and forty one cases with NPC and 272 matched cancer-free controls were genotyped for the CCND1 G870A and MMP-1(-1607)1G/2G polymorphisms by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing.The adjusted odds ratios(OR) and 95%confidence intervals(CI) were calculated by using unconditional logistic regression model.Overall survival was assessed using univariate and multivariate analyses.ResultsThe distribution of genotypes of CCND1 G870A and MMP-1(-1607)1G/2G genetic variants in cases and controls were consistent with Hardy-Weinberg equilibrium. For the CCND1 G870A polymorphism,the frequencies of the GG,AG and AA genotypes in the NPC and control group patients were 24.9%,45.6%,29.5%and 42.3%,45.6%,12.1%respectively.The frequency distribution of MMP-1(-1607) 1G1G,1G2G and 2G2G genotypes among NPC patients and controls was 15.8%, 41.5%,42.7%and 36.3%,44.5%,19.1%respectively.Contrast with homozygous CCND1 G870G,A allele significantly increasing risk of NPC was associated with homozygous A870A(OR=4.79,95%C 2.77—8.28, P＜0.001) and heterozygous A870G(OR=1.72,95%CI 1.10—2.68,P=0.017).The subjects at least having one CCND1 870A allele had OR of 2.40(95%CI 1.59—3.63, P＜0.001).We also found that the MMP-1(-1607)2G allele show a significant influence on the susceptibility to NPC(OR=4.35,95%CI 2.66～7.10,P＜0.001).By using the 1G1G genotype as reference,a significantassociation was found between the 2G2G genotype (OR=9.93,95%CI 5.38～18.32,P＜0.001) and in combination with 1G2G(OR =3.10, 95%CI 1.85～5.19,P＜0.001) and the risk of developing NPC.CCND1 870A allele is significantly associated with T3+T4(OR=1.593,P=0.013), Positive lymph nodes metastasis(OR=3.753,P＜0.001) andⅢ+Ⅳstages(OR=2.577, P＜0.001);In addition,An association was ascertained with MMP-1(-1607) 2G allele among T3+T4(OR=1.723,P=0.005),Positive lymph nodes metastasis(OR=2.864,P＜0.001) andⅢ+Ⅳstages(OR=1.529,P=0.042);While,no significant differences in genotype distribution of CCND1 G870A and MMP-1(-1607) 1G/2G polymorphisms were observed for gender and age(P＞0.05).Furthermore,Smoking may increase the risk of developing NPC interacting with CCND1 G870A and MMP-1(-1607) 1G/2G polymorphisms.The subjects with Smoking and at least having one CCND1 870A allele or MMP-1(-1607) 2G allele had an OR of 28.15(P＜0.001) or OR of 9.64(P＜0.001),compared with noncarriers and nosmokings.Our findings show that CCND1 870A allele and MMP-1(-1607) 2G allele were associated wih poor prognostic.Kaplan-Meier analysis and Cox regression analysis demonstrated that the five-year survival rate of subjects with CCND1 870AA,AG and GG genotype was 56.2%,78.5%and 81.4%(AA vs GG,P=0.003;AA vs AG,P=0.012; AG vs GG P=0.132),but not independent prognostic factor in NPC(RR＜1,P=0.501). The five-year survival rate of subjects with MMP-1(-1607)2G2G,1G2G and1G1G genotype was 60.1%,77.2%,82.6%(2G2G vs 1G1G,P=0.032;2G2G vs 1G2G, P=0.012;1G2G vs 1G1G,P=0.440).Especially,MMP-1(-1607) 2G2G genetype is independent prognostic factor in NPC(RR=3.10,P＜0.001).ConclusionsThe CCND1 870A allele and MMP-1(-1607) 2G allele are associated with the NPC in Han population in Yunnan China,meanwhile,showed a significant prognosis for those patients.The genetic variations may represent markers for the increased risk of nasopharyngeal carcinoma.
|