The correlation and significance of gene polymorphisms of C1236T, G2677T/A and C3435T with molecular subtypes of breast cancer

LIU Xinlan; ZHANG Haixia; LIU Yaobang; JIANG Min

doi:10.11958/20150238

Abstract：Objective To investigate the distribution of the MDR1 exon12 (C1236T), exon21 (G2677T/A) and exon 26 (C3435T) gene polymorphisms in breast cancer patients, and to analyse their relationship with molecular subtypes of breast cancer. Methods The genotyping of C1236T, G2677T/A and C3435T were detected by polymerase chain reaction (PCR)-high resolution melting (HRM) method in 400 cases of breast cancer. The Hardy-Weinberg equilibrium test was used for ge?netic equilibrium distribution of genotype. The molecular subtypes of breast cancer were classified based on St.Gallen Con?sensus 2013. The genotype distributions of C1236T, G2677T/A and C3435T in breast cancer were analyzed. Their relation?ship with molecular subtypes in breast cancer was analyzed as well. Results ①In 400 cases of breast cancer, there were 2, 3 and 2 specimens did not get genotyping results in C1236T, G2677T/A and C3435T genotype detection. The CC, CT and TT genotypes of C1236T accounted for 16.08% (64/398), 44.22% (176/398) and 39.70% (176/398). GG, GT, GA, TT and AT genotypes of G2677T/A accounted for 16.62%(66/397), 44.33%(176/397), 7.05%(28/397), 27.46%(109/397) and 4.54%(18/397). CC, CT and TT genotypes of C3435T accounted for 21.11%(84/398), 56.03%(223/398) and 22.86%(91/398) re?spectively. Hardy-Weinberg genetic equilibrium testing showed that polymorphisms of C1236T, G2677T/A and C3435T had group representation (P<0.05).②Eleven cases of HER-2 (2+) were excluded because they were not verified by FISH de?tection when performed molecular subtype of breast cancer. Luminal A subtype accounted for 41.90%(163/389), Luminal B subtype accounted for 32.65%(127/389), HER-2 over-expression subtype accounted for 13.62%(53/389) and triple nega?tive subtype accounted for 11.83%(46/389).③CT/TT genotype frequency of C3435T was significantly higher in breast can?cer patients with Luminal A subtype than that in breast cancer patients with HER-2 over-expression subtype and triple neg?ative subtype (χ2=12.011, P=0.001;χ2=13.976, P<0.001), while there was no statistical difference in C1236T and G2677T/A gene polymorphism between different molecular subtypes of breast cancer (P>0.05). Conclusion C3435T gene polymor?phism can explain more accurately heterogeneity of breast cancer. CT/TT genotype in different molecular subtypes of breast cancer may be more sensitive to drug treatment.