Genetic variation of PSCA gene is associated with the risk of both diffuse‐ and intestinal‐type gastric cancer in a Chinese population

Prostate stem cell antigen (PSCA), a member of the LY‐6/Thy‐1 family of glycosylphosphatidylinositol‐anchored cell surface proteins, is considered to be involved in the cell‐proliferation inhibition and/or cell‐death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case–control study including 1,053 incident gastric cancer patients and 1,100 cancer‐free controls in a high‐risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR =1.37, 95% CI = 1.15–1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal‐type gastric cancer (p = 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR = 1.14, 95% CI = 0.96–1.36). A small meta‐analysis including 5 case–control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR = 1.83, 95% CI: 1.29–2.60 and OR = 1.84, 95% CI: 1.33–2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.     

XRCC1 gene polymorphisms and esophageal squamous cell carcinoma risk in Chinese population: A meta‐analysis of case–control studies

Two non‐synonymous polymorphisms Arg194Trp and Arg399Gln in the DNA‐base excision repair gene X‐ray repair cross‐complementing group 1 (XRCC1) have been implicated in risk for esophageal cancer. However, the results from different studies remain controversial. The present meta‐analysis of literatures was performed to clarify these associations in Chinese population. A comprehensive literature search was conducted to identify all case–control studies of XRCC1 polymorphisms Arg194Trp and Arg399Gln and risk for esophageal squamous cell carcinoma (ESCC). A total of 9 eligible studies, including 1,538 ESCC cases and 2,472 controls, were identified to the meta‐analysis. The odds ratio (OR) for the variant homozygous genotype Trp/Trp of the Arg194Trp polymorphism, compared with the wild‐type homozygote Arg/Arg, was 1.59 (p = 0.0007), with 95% confidence interval (95% CI) 1.22–2.09, for ESCC risk without between‐study heterogeneity. However, there was no statistically significant associations of ESCC risk in the dominant model Arg/Trp+Trp/Trp (OR 0.97; 95% CI 0.84–1.12; p = 0.69) and heterozygous genotype Arg/Trp (OR 0.90; 95% CI 0.77–1.04; p = 0.16) when comparing with wild‐type genotype Arg/Arg. For Arg399Gln, there was no effect in dominant modeling (Arg/Gln+Gln/Gln vs. Arg/Arg: OR 0.92; 95% CI 0.80–1.06; p = 0.25), and the variant Gln/Gln homozygote was not associated with ESCC risk (OR 1.29; 95% CI 0.79–2.10; p = 0.31), either. In conclusion, Arg194Trp genetic polymorphism may be associated with an increased risk for developing ESCC and a study with the larger sample size is needed to further evaluate gene–environment interaction on XRCC1 polymorphisms and ESCC risk. © 2009 UICC     

XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital‐based case‐control study

In mammalian cells, X‐ray repair cross‐complementing group3 (XRCC3) plays an important role in the DNA double‐strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in the XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to gliomas. In this study, we used a haplotype‐based approach to investigate whether 4 tagging single nucleotide polymorphisms of the XRCC3 gene are associated with risk of gliomas in 771 glioma patients and 752 cancer‐free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, and haplotype associations were estimated using Haplo.Stat. After adjustment for age and sex, the variant G allele of rs861530 and T allele of rs3212092 were significantly associated with an increased risk of gliomas (AG/GG versus AA: adjusted OR = 1.44, 95% CI = 1.15–1.80, p = 0.001 and CT/TT versus CC: adjusted OR = 1.66, 95% CI = 1.12–2.46, p = 0.013, respectively). Consistent with these results, XRCC3 haplotype “GGCC” containing rs861530 G allele and haplotype “AGTC” containing rs3212092 T allele were also significantly associated with an elevated risk of gliomas compared with the common haplotype “AGCC” (adjusted OR = 1.35, 95% CI = 1.14–1.58, p = 0.000 and adjusted OR = 1.67, 95% CI = 1.11–2.52, p = 0.015, respectively). Our results suggest that common genetic variants in the XRCC3 gene may modulate glioma risk. © 2009 UICC     

Prevalence of high‐risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population—A pooled analysis from three studies

Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community‐based studies to report the high‐risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age‐adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age‐adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high‐risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high‐grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening.     

Body mass index and risk of gastric cancer: A 30‐year follow‐up study in the Linxian general population trial cohort

Although a number of previous studies have noted either positive or no association for body mass index (BMI) and gastric cancer risk, little evidence exists in the Chinese population. We prospectively examined the associations of BMI with risk of gastric cancer in the Linxian General Population Trial cohort, with 29 584 healthy adults enrolled in 1985 and followed through to the end of 2014. Body weight and height were measured during physical examination at baseline and BMI was calculated as weight in kilograms divided by height in meters squared. Body mass index from 138 subjects was missing, and a total of 29 446 participants were included in the final analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. During 30 years of follow‐up, we confirmed 1716 newly diagnosed gastric cardia adenocarcinoma (GCA) cases and 626 new gastric non‐cardia adenocarcinoma (GNCA) cases. Overall, compared to the lowest quartile (BMI <20.32 kg/m²), subjects in the fourth quartile (BMI ≥23.31 kg/m²) subjects had lower risk of developing GNCA (hazard ratio, 0.65; 95% confidence interval, 0.51–0.83). Age‐ and sex‐specific analyses showed that this protective effect was only observed in men and older (52 + years) persons. No associations were observed for BMI with GCA incidence. Higher BMI was associated with decreased risk of GNCA in this population, particularly in men and older persons. Future studies are needed to confirm these findings. The trial is registered with ClinicalTrials.gov: NCT00342654.     

Analysis of Bcr‐Abl kinase domain mutations in Korean chronic myeloid leukaemia patients: poor clinical outcome of P‐loop and T315I mutation is disease phase dependent

Despite durable responses to imatinib in chronic myeloid leukaemia (CML), mutations in Bcr‐Abl kinase domain (KD) are known to induce imatinib resistance and cause poor clinical outcome. We characterized Bcr‐Abl KD mutations in 137 Korean CML patients with imatinib resistance (n = 111) or intolerance (n = 26) using allele specific oligonucleotide polymerase chain reaction (PCR) and direct sequencing. Seventy (51%) patients harboured 81 mutations of 20 different types with increasing prevalence in advanced phase. Nine (13%) patients had multiple mutations. No mutation was found in intolerant patients. T315I was the most common mutation and P‐loop was the hottest spot in Bcr‐Abl KD. Patients harbouring P‐loop mutation, T315I, or multiple mutations showed poor overall survival and progression free survival compared with patients harbouring other mutations. Survival analysis according to disease phase of mutation being detected and type of mutations provided correlation between P‐loop or T315I mutation and poor overall survival in blast crisis, but not in accelerated phase (AP) or chronic phase (CP), indicating poor clinical outcome of particular mutations depends on disease phase. CML patients with imatinib resistance showed high rate (63%) of mutations in Bcr‐Abl KD and therefore CML patients who do not respond to imatinib should be the candidates for mutation screening as molecular monitoring. Copyright © 2009 John Wiley & Sons, Ltd.     

Relationship between response rates and median progression‐free survival in non‐Hodgkin's lymphoma: A meta‐analysis of published clinical trials

Demonstration of clinical effectiveness of a non‐Hodgkin's lymphoma (NHL) treatment generally involves determination of progression‐free survival (PFS). However, the long evaluation time of PFS limits its utility to make timely decisions in drug development. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in NHL. A database was systematically developed from 513 identified NHL trials reported from 1996 to 2015. Potential predictors of the relationship between response rates and PFS were evaluated, including age, sex, treatment, percentage of treatment‐naïve patients, and subtype of NHL. Seventy‐three trials involving 86 cohorts were included in the meta‐analysis. Linear regression analysis using logit of response rates and logarithm of median PFS indicated that the correlation between overall response rate (ORR) and median PFS was higher (R² = 0.70) when compared to that of complete response (CR) rate and median PFS (R² = 0.57). Furthermore, the correlation was improved with the addition of percentage of treatment‐naïve patients and percentage of patients with follicular lymphoma (FL) (P < .005) between ORR and median PFS (R² = 0.78), and between CR rate and median PFS relationship (R² = 0.74). Treatment was not found to alter this relationship. In summary, ORR is as good as CR rate in predicting median PFS. Moreover, longer median PFS is expected in the trials including treatment‐naïve and/or FL patients at a given ORR/CR rate. The determined relationship can be used to project the median PFS based on ORR or CR rate.     

Incidence of lymphoplasmacytic lymphoma/Waldenström's macroglobulinaemia in Japan and Taiwan population‐based cancer registries, 1996–2003

Few studies have investigated the incidence rate of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) in Asian populations. We assessed the incidence of LPL/WM using data from 13 population‐based cancer registries in Japan and data from the Taiwan National Cancer registry. During 1996–2003, a total of 280 new cases of LPL/WM were recorded in Japan and 56 were recorded in Taiwan, with the median age at diagnosis being 73 and 67 years, respectively. The incidence of LPL/WM showed male predominance in both countries. Crude age‐specific incidence rates increased sharply with age in both countries, especially in people >65 years. Age‐standardized (to the World standard population) incidence rates per 100,000 person‐years were 0.043 (0.071 for men and 0.023 for women) and 0.031 (0.041 for men and 0.020 for women) in Japan and Taiwan, respectively. Age‐standardized (to the 2,000 US standard population) incidence rates in Japan and Taiwan were lower than rates reported in the literature for Asians living in the United State. A significant increasing trend was observed in the incidence over the period from 1996 to 2003 in Japan alone. This report suggests that both environmental and/or genetic factors may be involved in LPL/WM development.     

Effectiveness of telephone‐based interventions on health‐related quality of life and prognostic outcomes in breast cancer patients and survivors—A meta‐analysis

The aim of this meta‐analysis was to evaluate the effect of telephone‐based interventions on prognostic outcomes and health‐related quality of life (HRQoL) in breast cancer patients and survivors. A systematic search of the Cochrane Library, Web of science, Medline, EMBASE, CNKI and CBM database was carried out. Randomised, controlled trials (RCTs) examining the effects of telephone‐based intervention versus a control group receiving no telephone intervention, on prognostic outcomes and HRQoL with breast cancer were included. A meta‐analysis was conducted to quantify the effects of telephone‐based interventions on anxiety, depression, fatigue, self‐efficiency, physiological function, social‐domestic function and quality of life. In total, 14 studies involving 2002 participants were included. Due to the effect of telephone‐based interventions, statistically significant results were found on anxiety (standard mean difference [SMD] = ?0.16, 95% confidence intervals [CI] [0.01, 0.30], p = .04), self‐efficiency (SMD = 0.22, 95% CI [?0.34, ?0.10], p = .0004), social‐domestic function (SMD = 0.19, 95% CI [?0.35, ?0.03], p = .02) and quality of life (SMD = 0.54, 95% CI [?1.00, ?0.08], p = .02). Although the effects on depression, fatigue and physiological function were in the expected direction, these effects were not statistically significant (p > .05) based on the insufficient evidence.