Lymphotoxin Alpha (<i>LTA</i>) Polymorphism Is Associated with Prognosis of Non-Hodgkin’s Lymphoma in a Chinese Population

<div><p>Background</p><p>Non-Hodgkin’s lymphoma (NHL) has been widely reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the survival and prognosis of NHL patients. To evaluate the role of such genetic variations in prognosis of NHL, we conducted this study in a Chinese population.</p><p>Methods</p><p>We used the TaqMan assay to genotype six single nucleotide polymorphisms (SNPs) (<i>TNF</i> rs1799964T>C, <i>LTA</i> rs1800683G>A, <i>IL-10</i> rs1800872T>G, <i>LEP</i> rs2167270G>A, <i>LEPR</i> rs1327118C>G, <i>TNFAIP8</i> rs1045241C>T) for 215 NHL cases. Kaplan-Meier analysis was performed to compare progression free survival among two common genotypes. Cox proportional hazard models were used to identify independent risk factors.</p><p>Results</p><p>We observed that <i>LTA</i> rs1800683G>A was significantly associated with risk of progression or relapse in NHL patients (HR = 1.63, 95%CI = 1.06–2.51; <i>P</i> = 0.028), particularly in Diffuse large B cell lymphoma (DLBCL) cases (HR = 1.50, 95%CI = 1.10–2.04, <i>P</i> = 0.01). Both univariate and multivariate Cox regression analysis showed that in DLBCL patients, Ann Arbor stage III/IV, elevated LDH level before treatment and <i>LTA</i> rs1800683 AA genotype carrier were independent risk factors for progression or relapse. While in NK/T cell lymphoma, Ann Arbor stage III/IV and elevated β₂-MG level before treatment indicated poorer prognosis.</p><p>Conclusions</p><p>The polymorphism of <i>LTA</i> rs1800683G>A contributes to NHL prognosis in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.</p></div

Clinical characteristics of 215 NHL cases.

<p>Clinical characteristics of 215 NHL cases.</p

Univariate and multivariate analysis for PFS in DLBCL cases.

<p>Univariate and multivariate analysis for PFS in DLBCL cases.</p

Univariate and multivariate analysis for PFS in NK/T-cell lymphoma cases.

<p>Univariate and multivariate analysis for PFS in NK/T-cell lymphoma cases.</p

Relationship between P53 Status and Response to Chemotherapy in Patients with Gastric Cancer: A Meta-Analysis

<div><p>Background</p><p>Previous studies have yielded conflicting results regarding the relationship between p53 status and response to chemotherapy in patients with gastric cancer. We therefore performed a meta-analysis to expound the relationship between p53 status and response to chemotherapy.</p><p>Methods/Findings</p><p>Thirteen previously published eligible studies, including 564 cases, were identified and included in this meta-analysis. p53 positive status (high expression of p53 protein and/or a mutant p53 gene) was associated with improved response in gastric cancer patients who received chemotherapy (good response: risk ratio [RR]  = 0.704; 95% confidence intervals [CI]  = 0.550–0.903; P = 0.006). In further stratified analyses, association with a good response remained in the East Asian population (RR = 0.657; 95% CI = 0.488–0.884; P = 0.005), while in the European subgroup, patients with p53 positive status tended to have a good response to chemotherapy, although this did not reach statistical significance (RR = 0.828, 95% CI = 0.525–1.305; P = 0.417). As five studies used neoadjuvant chemotherapy (NCT) and one used neoadjuvant chemoradiotherapy (NCRT), we also analyzed these data, and found that p53 positive status was associated with a good response in gastric cancer patients who received chemotherapy-based neoadjuvant treatment (RR = 0.675, 95% CI = 0.463–0.985; P = 0.042).</p><p>Conclusion</p><p>This meta-analysis indicated that p53 status may be a useful predictive biomarker for response to chemotherapy in gastric cancer. Further prospective studies with larger sample sizes and better study designs are required to confirm our findings.</p></div

Forest plots of RR estimated for the relationship between p53 status and good response among gastric cancer patients treated with chemotherapy.

<p>Forest plots of RR estimated for the relationship between p53 status and good response among gastric cancer patients treated with chemotherapy.</p

Forest plots of RR estimated for the relationship between p53 status and good response to chemotherapy in East Asian population with gastric cancer.

<p>Forest plots of RR estimated for the relationship between p53 status and good response to chemotherapy in East Asian population with gastric cancer.</p

Criteria for response evaluation and standard definitions.

<p>WHO, World Health Organization; RECIST, Response Evaluation Criteria in Solid Tumors; JRSGC, Japanese Research Society for Gastric Carcinoma; CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease; NR, no record; NC, no change.</p

Risk ratio for the association between p53 positive status and good response to chemotherapy.

<p>Subgroup analysis was performed when at least five studies were in a subgroup.</p><p>N, number of studies; z, the test statistics of z test; P, p value of the z test; χ², the test statistics of I² statistic for heterogeneity; Ph, p value of the I² statistic.</p

Flow diagram illustrating the screening and selection process.

<p>Flow diagram illustrating the screening and selection process.</p