| Objectives The aim of this study was to investigate the association between rs1864182 polymorphism of ATG10 gene and the susceptibility,clinicopathological characteristics,and circulating tumor cells of breast cancer in Guangxi.Methods In the first part,women from Guangxi was taken as the research object.Based on the case-control study,195 female patients with breast cancer and 219 healthy controls were included.General data and clinicopathological characteritics were collected.About 5ml peripheral venous blood was collected and the whole blood DNA was extracted.After the whole blood DNA was subjected to polymerase chain reaction(PCR),the genotyping of rs1864182 was subsequently detected by direct sequencing.The differences in the general clinical data between the cases and controls were compared by t test or c2test.Odds ratios(OR)and 95% confidence intervals (CIs) was calculated.Univariate analysis and binary unconditioned logistic regression model was performed to analyze the association between rs1864182 polymorphism and the risk of breast cancer,as well as to evaluate stratification analysis and gene-environmental interaction.In the second part,patients with breast cancer in Guangxi province were selected as the subjects.Adjusted for confounding factors,the binary unconditioned logistic regression model was adopted to analyze the associations between rs1864182 polymorphism and the tumor sizes,TNM staging,axillary lymph node metastasis,ER,PR,HER-2,Ki-67,P53,P16 and circulating tumor cells(CTCs)of breast cancer.Results 1.Comparison of general clinical data: There were statistically significant differences in menarche age,body mass index(BMI),menopausal status and family history of breast cancer between cases and controls(P <0.05).No significant associations were observed in age,ethnicity or primiparous age(P>0.05).2.In the control group,the distribution of genotypes of ATG10 gene rs1864182 polymorphism was in the Hardy-Weinberg equilibrium(P> 0.05).3.The genotype frequencies of TT,GT and GG in rs1864182 locus of ATG10 gene were 79.5%(155/195),19.5%(38/195),1.0%(2/195)in the case group,respectively.The genotype frequencies in the control group were 76.3%(167/219),21.5%(47/219)and 2.3%(5/219),respectively.The gene frequencies of the allele T and G in rs1864182 were 89.2%(348/390)and 10.8%(42/390)in the case group,and 87.0%(381/438),13.0%(57/438)in the control group,respectively.Adjusted for some confounding factors,there was no statistically significant association between rs1864182 polymorphism and breast cancer susceptibility in the total population using unconditional logistic regression model(P> 0.05).4.Stratified analysis showed that carrying the variant allele(GT + GG)of rs1864182 might reduce the risk of breast cancer among women under 49 years old and in premenopausal status,compared with the TT genotype(among women under 49 years old: P = 0.038,adjusted OR=0.497,95%CI=0.256-0.963,and among premenopausal women: P = 0.048,adjusted OR=0.537,95%CI=0.290-0.993).5.Gene-environmental interaction : Interaction between gene and environmental factors was found between rs1864182 polymorphism and menopausal status(P = 0.039).6.There was no correlation between the rs1864182 polymorphism of ATG10 gene and the tumor sizes,TNM stage,histological grade,axillary lymph node metastasis status,ER,PR,HER-2,P53 and Ki-67 of breast cancer(P>0.05).Breast cancer patients with GT genotype and the variant allele of rs1864182(GT + GG)might associated with P16 expression by unconventional logistic regression analysis,adjusted for age,menopausal status,pathologic type,histological grade and axillary lymph node metastasis status and other confounding factors.(for TT vs GT: P = 0.026,adjusted OR = 2.497,95% CI =1.118-5.579,for TT vs GT + GG: P = 0.041,adjusted OR = 2.219,95% CI =1.032-4.771).7.There were 72 patients with breast cancer conducted genotyping and CTCs detection.Among them,there were 54 cases with TT genotype,and 18 cases with GT genotype.CTCs were found in 60 patients(83.3%),and 12 patients were CTC-negative(16.7%).There were 47 patients(65.3%)with epithelial CTC,23 patients(31.9%)with mesenchymal CTC,and 45 patients(62.5%)with hybrid CTC.With respect to rs1864182 polymorphism,no significant association with the detection and number of CTCs and its subtypes was demonstrated(P> 0.05).Conclusions ATG10 gene rs1864182 polymorphism might reduce risk of breast cancer among women under 49 years old and premenopausal women in Guangxi province.Interaction between rs1864182 and environmental factors might associated with the risk of breast cancer.rs1864182 polymorphism might correlate to the P16 expression of breast cancer. |
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