Relationship Between DBC2 Gene Polymorphism And Clinical/Biological Behavior Of The Breast Cancer

Objective:DBC2, the main candidate tumor suppressor gene of breast cancer, was named in 2002. It is presumed expression absence or inactivity in most breast cancers. Recently, DBC2 was found to participate in diverse cellular functions such as protein transport, cytoskeleton regulation, apoptosis, and cell cycle control. Further research demonstrated that gene mutation, DNA promoter hypermethylation, ubiquitin proteasome degradation pathway may lead to the tumorigenesis. However, there was no report about the relationship of DBC2 polymorphism and breast cancer. There was no report about the relationship between DBC2 gene polymorphism and clinical /biological behavior of the breast cancer. In the present study, we examined the polymorphism of DBC2 gene in the peripheral blood of 104 breast cancer patients and 113 health control persons and analyzed the relationship between DBC2 gene polymorphism and clinical/biological behavior of the breast cancer.Methods:104 breast cancer patients and 113 health control persons were enrolled in our study. Polymerase Chain Reaction (PCR) and DNA sequencing were adopted to study the genetic polymorphism of DBC2 gene. The relationship between DBC2 gene polymorphism and the age, menstrual status, clinical stages, histological grades, the metastatic state of the axillary lymph nodes, estrogen receptor and progestogen receptor of all the breast cancer patients were analyzed.χ2 and Fisher of SPSS 12.0 statistical package was used to do the statistics analysis, p<0.05 was considerd significantly difference.Results:1. The age distribution of the 104 patients was 20～84, in which the median age was 52, The age distribution of the control group was 33-72,in which the median age was 47. There was no obvious difference in the distribution of the two groups(t=1.559;p=0.121).2. In the case group, there were 56 post-menopause people and 48 pre-menopause people, while in the control group, the number were 45and 68. There was no obvious difference in the distribution of menstruation condition(χ2=0.183;p=0.669).3. A novel missense mutation DBC2.864C>T (P,Leu288Phe) in the 5th exon was found in 13 of 104 breast cancer patients and 5 of 113 healthy control patients, and the mutation rate was 12.5% and 4.4%, respectively. The mutation rate of breast cancer patients was significantly higher than the healthy control group (χ2=4.643;p=0.031) (OR=3.086,95%CI=1.060-8.982), indicating that DBC2.864C>T was positively correlated with the risk of breast cancer.4. The clinical stage was analyzed. The number and percentage of Mutation group in stage I was 6(13.6%),stage II was 6(16.7%),and stage III was 1(4.2%), while the No mutation group was 38(86.4%),30(83.3%)and 23(95.8%). There was no obvious difference in the distribution of clinical stage(x2=2.147;p=0.342). DBC2.864C>T Polymorphism had no relationship with clinical stage.Compared with stage III, the OR of stage I and II was 3.624(95%CI=0.411～32.107)and 4.600(95%CI=0.517～40.921).5. The pathological type was analysed. In invasive ductal carcinoma, the number and percentage of Mutation group was 10(13.2%); In invasive lobular carcinoma, it was 2(16.7%); In other types, it was 1(6.3%). When it came to the No mutation group, the percentage was 66(86.8%),10(83.3%)and 15(93.7%). There was no statistical difference in genotypes distribution(χ2=0.792;p=0.673).DBC2.864C>T Polymorphism had no relationship with pathological type. Compared with invasive lobular carcinoma, the OR of invasive lobular carcinoma and other cancer was 1.320(95%CI=0.252-6,925)and 0.440(95%CI=0.052-3.705).6. The tumor size was analyzed in the 104 pantients. The number and percentage of Mutation group in T≤2cm group was 8(13.1%)in T>2cm group was 5(11,6%)and, while No mutation group was 53(86.9%) and 38(88.4%). There was no obvious difference in the distribution of gentpyes(x2=0.051;p=0.821). DBC2.864C>T Polymorphism had no relationship with the size of tumor and the OR was 0.872(95%CI=0.265～2.873).7. The number of axillary lymphnode metastases was analyzed. The number and percentage of Mutation group in negative group was 7(11.3%), in positive group was 6(14.3%),while the No mutation group was 55(88.7%) and 36(85.7%). there was no statistical difference in genotypes distribution(x2=0.205;p=0.650).DBC2.864C>T Polymorphism had no relationship with lymphnode metastases. Compared with negative group, the OR of positive group was 0.764(95%CI=0.237-2.457).8. The histological grade was analyzed. The number and percentage of Mutation group in gradeⅠ～Ⅱgroup was 12(13.8%), and in gradeⅢgroup was 1(5.9%), while the No mutation group was 75(86.2%)and 16(94.1%). there was no statistical difference in histological grade (Fisher=0.689;p=0.330). Compared with the no mutation group, the OR of positive group was 0.391(95%CI=0.047-3.223).9. The expression of ER protein was analysed. The number and percentage of Mutation group in ER (-) group was 2(24.0%), in ER (+)～(++) group was 4(11.4%), in ER (+++) group was 5(10.5%) ER unknown was 2(13.3%); while the No mutation group was 17(89.2%), 31(88.6%),30(85.7%) andl3(86.2%). There was no obvious difference between the 2 groups.(x2=0.216;p=0.915). DBC2.864C>T Polymorphism had no relationship with ER expression. Compared with ER (-)group, the OR of ER (+)～(++) group,ER (+++) group was 1.097 (95% CI=0.182～6.618) and 1.417 (95%CI=0.248-8.107)10. The expression of ER protein was analysed. The number and percentage of Mutation group in PR (-) group was 2(10.0%), in PR (+)～(++) group was 4(9.1%), in PR (+++) group was 5(20.0%) PR unknown was 2(13.3%); while the No mutation group was 18(90.0%), 40(90.9%),20(80.0%)and 13(86.7%).There was no obvious difierence between the 2 groups.(χ2=0.1.877；p=0.598).DBC2.864C>T Polymorphism had no relationship with PR expression.Compared with PR(一)group,the OR of PR (+)～(++) group, ER (+++) group was 0.900 (95%CI=0.151～5.370)and2.250(95%CI=0.387～13.067)11.The expression of C-erb-B2 protein was analysed.The number and percentage of Mutation group in C-erb-B2(一)group was 1(5.0%),in C-erb-B2(+)-(++)group was 3(6.1%),in C-erb-B2(+++)group was 7(38.1％)C-erb-B2 unknown was 2(13.3%)；while the No mutation group was 13(86.7%),46(93.9%),15(68.2%)and 13(86.7%).The difference between the two groups was notable(χ2=10.5322；p=0.015)..Compared with the C-erb-B2(+++)group,the OR of C-erb-B2(+)～(++)group,C-erb-B2 (+++) group was 7.15 (95%CI=1.641-31.206 and9.500 (95%CI=1.046～86.261).Conclusion:1.DBC2.864C>T Gene Polymorphism in northern China may be related to the occurrence of breast cancer in women,DBC2.864C>T was positively correlated with the risk of breast cancer.2.DBC2.864C>T Gene Polymorphism was positively correlated with C-erb-B2 expression.3.There was no relationship between the DBC2.864C>T polymorphism of and clinical stae,pathology type,tumor size,the expression of ER,PR of breast cancer.