ABSTRACT
Objective@#To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.@*Methods@#Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios (HRs) and 95% CIs by Cox proportional regression model.@*Results@#Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P=0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P=0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer (HR=0.44, 95% CI: 0.20-0.96, P=0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time (HR=1.74, 95% CI: 1.06-2.84, P=0.028; HR=1.64, 95% CI: 1.01-2.66, P=0.046; HR=1.71, 95% CI: 1.01-2.91, P=0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis.@*Conclusions@#Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.
ABSTRACT
Objective Analysing the potential relationship of mismatch repair protein MLH3 gene C2531T mutation with oligospermia and azoospermia cases. Methods Using MLH3 C2531T as an example to establish a method of tetra-primer amplification refractory mutation system-PCR (4P-ARMS-PCR); We chose 81 cases of oligospermia, azoospermia patients and 80 normal controls, detecting MLH3 C2531T both using 4P-ARMS-PCR and PCR-RFLP; randomly to select 20% samples to sequence. Results The results suggested higher prevalence of CT + TT genotypes in patients as compared to the controls and association of T allele with disease (P <0. 01); PCR-RFLP results , 4P-ARMS-PCR results and sequence results are fully consistent. Conclusion 4P-ARMS-PCR can be a fast, easy-operating and accurate technology for detection of gene mutation of single nucleotide polymorphism (SNP) ; MLH3 C2531T polymorphism is related to oligospermia and azoospermia.
ABSTRACT
Objective Analysing the potential relationship of mismatch repair protein MLH3 gene C2531T mutation with oligospermia and azoospermia cases. Methods Using MLH3 C2531T as an example to establish a method of tetra-primer amplification refractory mutation system-PCR (4P-ARMS-PCR);We chose 81 cases of oligospermia,azoospermia patients and 80 normal controls,detecting MLH3 C2531T both using 4P-ARMS-PCR and PCR-RFLP; randomly to select 20% samples to sequence. Results The results suggested higher prevalence of CT+TT genotypes in patients as compared to the controls and association of T allele with disease(P