Title: Abstract P3-08-23: T146A/C and C16266T/A/G,D-loop region SNPs in mtDNA, were acted as potential targets for early breast cancer in Chinese women
Abstract: Abstract Purpose: Aimed to detected the association between mtDNA D-loop region nucleotide polymorphisms and prognosis of early-stage breast cancer (EBC) patients in a Chinese Han population. Material and Method: we detected 344 nucleotides in the entire mitochondrial D-loop region of each EBC cases (a total of 714) by Sanger sequencing to evaluate the relationship of mtDNA nucleotide polymorphisms and outcomes of EBC patients with a median time of follow-up was 81 months (see table1). Result: A multivariate survival analysis from the Cox proportional hazards regression models showed that two SNPs, T146A/C and C16266T/A/G, have a statistically significant association with recurrence and death in early breast cancer patients: The adjusted HR for iDFS and BCSS are 1.39 (95% CI 1.05-1.85, p = 0.023) and 1.41 (95% CI 1.04-1.93, p = 0.028) for T146A/C, respectively. The combined action analysis of two SNPs found that iDFS: adHR=1.407 (1.122-1.766), p = 0.0032; DDFS: adHR=1.366 (1.083-1.723), p = 0.0085; BCSS: adHR=1.475 (1.149-1.895), p = 0.0023;OS: adHR=1.380(1.074-1.774), p = 0.0117(see table 2). The ROC curve analysis shows that the prediction of survival when using clinicopathological characteristics and two SNPs are better than using clinicopathological factors alone (for BCSS, AUROC = 0.7407 VS 0.7569, p = 0.0344; for OS AUROC = 0.7359 vs 0.7473, p = 0.0340. see figure 1a. 1b),especially for patients with tumor size >2cm(for BCSS, p = 0.0361. see figure 1c). Conclusion: This present research is the first time to suggest that T146A/C and C16266T/A/G (D-loop region SNPs in mtDNA) may influence the outcomes of EBC patients. Based on these results, we call for further investigations to confirm these findings. Keyword: Breast cancer, D-loop region, Single nucleotide polymorphism, Mutation, Prognosis Table 1. Basic clinicopathological characteristics and four outcomes for EBC cases.VariablesCasesaiDFSDDFSBCSSOSeventsLog-rank peventsLog-rank peventsLog-rank peventsLog-rank pAge at diagnosis0.01550.00210.48440.4870≤ 358647464141> 35628291280236241Tumor size711<0.0001<0.0001<0.0001<0.0001≤ 2cm23367645354>2cm478268259222226Tumor size714<0.0001<0.0001<0.0001<0.0001Negative28088846366Positive434250242214216Stage713<0.0001<0.0001<0.0001<0.0001I14331292525II330139133102106III240167163150151Grade711<0.0001<0.0001<0.0001<0.0001I14741393636II396189184149153III1681051008990ER714<0.0001<0.0001<0.0001<0.0001Negative250148143132133Positive464190183145149PR714<0.0001<0.0001<0.0001<0.0001Negative318185178160161Positive396153148117121HER-2712<0.0001<0.0001<0.0001<0.0001Negative498207201167171Positive215130124109110Subtype710<0.0001<0.0001<0.0001<0.0001Luminal A13627272222Luminal B324161154122126HER-2 Over-expression10974716464Triple negative14173716768 Table 2. Association between the SNPs with EBC survival (multivariate cox proportional hazard model).SNPs(iDFS)(DDFS)(BCSS)(OS)adHR (95% CI) P valueadHR (95% CI) P valueadHR (95% CI) P valueadHR (95% CI) P valueT146C/A1.39 (1.05-1.85)0.0231.33 (1.00-1.78)0.0531.41 (1.04-1.93)0.0281.36 (1.00-1.86)0.049C16266T/G/A0.62 (0.40-0.98)0.0420.64 (0.40-1.01)0.0560.54 (0.31-0.92)0.0240.64 (0.39-1.07)0.09T146C/Aand C16266T/G/A1.407(1.05-1.85)0.0321.366 (1.083-1.723)0.00851.475 (1.149-1.895)0.00231.380 (1.074-1.774)0.0117P-values less than0.05 were considered statistically significant.aAdjusted for age at diagnosis, ER status, PR status, HER-2 status, tumor size, lymph nodes status, grade. Figure1 The ROC curve for clinicopathological factors and two SNPs(T146A/C and C16266T/A/G polymorphisms)in total patients Citation Format: Songping Lin, Fangmeng Fu, Fangmeng Fu, Bangwei Zeng, Lili Chen, Yuxiang Lin, Chuanwang Wang. T146A/C and C16266T/A/G,D-loop region SNPs in mtDNA, were acted as potential targets for early breast cancer in Chinese women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-23.
Publication Year: 2020
Publication Date: 2020-02-15
Language: en
Type: article
Indexed In: ['crossref']
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