The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

Age–period–cohort analysis of colorectal cancer in East Anglia, 1971–2005

Background: This study aimed to investigate the incidence trends of colorectal cancer by sex and subsite, in East Anglia from 1971 to 2005. Methods: Using data from the Eastern Cancer Registration and Information Centre, we examined the time trends and the effect of age, period of diagnosis and birth cohort on the incidence of colorectal cancer by sex and subsite. Results: Between 1971 and 2005, 23 875 males and 22 651 females were registered with colorectal cancer in East Anglia. During this period, the increase in the incidence trends was higher among males, more recent periods of diagnosis, and proximal colon. Cohort effects were statistically significant in distal and rectal cancers in males (p < 0.001 and p = 0.05, respectively), and in proximal colon in females (p < 0.001). Period effects were statistically significant across all subsites and both sexes (p < 0.001 for all). Conclusions: Period effects were significant across all subsites for both sexes, whereas cohort effects varied in their significance levels depending on subsite and sex. We suggest that the period effect may be due to an increase in the use of colonoscopy for diagnostic or opportunistic screening, and the cohort effect may be due to aetiological differences in CRC between sexes and subsites.     

Meta-analysis of the clinicopathological characteristics and peri-operative outcomes of colorectal cancer in obese patients

BackgroundThe effect of obesity on the clinicopathological characteristics of colorectal cancer (CRC) has not been clearly characterized. This meta-analysis assesses the pathological and perioperative outcomes of obese patients undergoing surgical resection for CRC.MethodsMeta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies reporting outcomes for obese and non-obese patients undergoing primary CRC resection, based on body-mass index measurement. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI).ResultsA total of 2183 citations were reviewed; 29 studies comprising 56,293 patients were ultimately included in the analysis, with an obesity rate of 19.3%. Obese patients with colorectal cancer were more often female (OR 1.2, 95% CI 1.1–1.2, p < 0.001) but there was no difference in the proportion of rectal cancers, T4 tumours, tumour differentiation or margin positivity. Obese patients were significantly more likely to have lymph node metastases (OR 1.2, 95% CI 1.1–1.2, p < 0.001), have a lower nodal yield, were associated with a longer duration of surgery, more blood loss and conversions to open surgery (OR 2.6, 95% CI 1.6–4.0, p < 0.001) but with no difference in length of stay or post-operative mortality.ConclusionThis meta-analysis demonstrates that obese patients undergoing resection for CRC are more likely to have node positive disease, longer surgery and higher failure rates of minimally invasive approaches. The challenges of colorectal cancer resection in obese patients are emphasized.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

Overexpression of the Interferon regulatory factor 4-binding protein in human colorectal cancer and its clinical significance

Background: IFN regulatory factor 4-binding protein (IBP) is a novel type of activator of Rho GTPases. It has been linked with differentiation and apoptosis of lymphocytes, but its function in oncogenesis remains unclear. Here we studied the expression of endogenous IBP in four human colorectal cancer cell lines, normal, adenoma and tumor colorectal tissues. Methods: Molecular (Western blot and RT-PCR), and confocal analyses were used to investigate IBP expression in human colorectal cancer cell lines. Matched normal and tumor tissue sections of 63 patients and 15 adenoma tissue sections were analyzed for IBP expression by immunohistochemistry (IHC). Results: IBP was ubiquitely expressed in human colorectal cancer cell lines. The expression of IBP can be detected at both the mRNA and protein level in SW480, SW620 and HT29 cells. Clinically, IBP were elevated in human colorectal cancer specimens in comparison to normal colorectal tissues. Substantial high expression of IBP was observed in colorectal cancer tissues (67%), whereas corresponding normal tissues and 15 adenoma tissues showed consistently absent immunoreactivity of IBP. Moreover, IBP expression is correlated with the differentiation level of colorectal cancer cells (p < 0.05) and clinical stage of patients (p < 0.01). Conclusions: Our data show, for the first time, a dysregulated expression of IBP in human colorectal cancer, offering new perspectives for its role in cancer development and progression. IBP may be a novel tumor marker and a therapeutic target for colorectal cancer.     

Trends and inequities in colorectal cancer screening participation in Ontario,Canada, 2005–2011

Background: Participation in screening tests for colorectal cancer (CRC) is generally low in Ontario, Canada. In addition, inequities in participation exist including lower participation among low-income individuals, males and individuals living in rural areas. In April 2008, Colon Cancer Check (CCC) program, the province-wide CRC screening program, was launched in Ontario. This study describes the trends and inequities in CRC screening participation three years before and three years after the CCC, and assesses the effect of the program on CRC screening participation, overall and among certain population groups. Methods: We used administrative data to identify cohorts of individuals eligible for CRC screening in fiscal years 2005–2011. We calculated the age-standardized percent of Fecal Occult Blood Test (FOBT) participation, large bowel endoscopy participation, and being ‘up-to-date’ with CRC screening tests. Results: From 2005 to 2011, FOBT participation increased from 7.6% to 14.8%, large bowel endoscopy participation from 3.4% to 5.7%, and ‘up-to-date’ with CRC screening from 27.2% to 41.3%. Before the launch of the CCC program, the quarterly increase in FOBT participation was 0.07% (p = 0.19), increased immediately after the launch (1.8%, p < 0.01), followed by a decline (?0.08%, p = 0.08), returning to its pre-program increase rate. We noted a significant decrease in FOBT participation every summer (?0.44%, p < 0.01). The CCC program had minimal effect on large bowel endoscopy participation. Before the launch of the CCC program, the quarterly increase in ‘up-to-date’ with CRC screening was 0.9% (p < 0.01), increased immediately after the launch (2.5%, p = 0.05), followed by a modest decline thereafter (?0.59%, p < 0.02). From 2005 to 2011, recent residents living in low-income neighborhoods were consistently and significantly less likely to have a FOBT and be ‘up-to-date’ with CRC screening than long-term residents living in high-income neighborhoods (2.9–4.5%; 14.7–17.3% respectively). Pre-CCC inequities in CRC participation persisted after the launch of the program. Conclusion: CRC testing was increasing in Ontario from 2005. An immediate increase in CRC testing, FOBT in particular, occurred after the launch of the CCC program, followed by a return to its pre-CCC increase rate thereafter. Future efforts are needed to improve screening participation and address inequities.     

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR = 2.58, 95% CI = 1.77–3.77, p < 0.05) and Pro/Pro mutant homozygosity (adjusted OR = 2.92, 95% CI = 1.78–4.78, p < 0.05) along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR = 2.70, 95% CI = 1.90–3.82, p < 0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p < 0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR = 2.02, 95% CI = 1.42–2.87, p < 0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.     

Polymorphisms in methyl-group metabolism genes and risk of sporadic colorectal cancer with relation to the CpG island methylator phenotype

Background: The CpG island methylator phenotype (CIMP), together with extensive promoter methylation, is regarded as one of the mechanisms involved in colorectal carcinogenesis. The mechanisms underlying CIMP in sporadic colorectal cancer are poorly understood. Genes involved in methyl-group metabolism are likely to affect DNA methylation and thereby influence an individual's risk of CIMP. The aim of the present study was to evaluate whether polymorphisms in the genes encoding methyl-group metabolism pathway predispose to CIMP+ and/or CIMP? CRC. Methods: We examined the potential association between the polymorphisms of MTHFR 677C>T, TS 5′UTR 2R/3R, TS 3′UTR 1494del6, ΔDNMT3B ?149C>T and DNMT3B ?283T>C in a group of 46 CIMP+ CRC cases, 140 CIMP? CRC cases and 140 healthy controls. The CIMP status of the CRC cases was determined by MS-PCR in tumor tissue by a panel of five markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), which was also followed by analyzing hMLH1 methylation and BRAF V600E mutation. Results: The variant allele homozygote genotype for the ΔDNMT3B ?283T>C polymorphism was associated with a decreased risk for CIMP+ CRC (OR: 0.31, 95%CI: 0.09–0.73, p = 0.009). Individuals with TS 3R/3R had an increased risk of CIMP? CRC (OR: 2.21, 95%CI: 1.23–4.91, p = 0.01). Moreover, the carriers of 3R allele had an increased risk of CIMP? CRC (OR: 1.45, 95%CI: 1.10–2.13, p = 0.01). Conclusion: This study provides support to the hypothesis that methyl-group metabolism plays a role in the etiology of both CIMP+ and CIMP? colorectal cancers but has a different impact on a distinct molecular subgroups of colorectal cancer.     

Community-based colorectal cancer intervention in underserved Korean Americans

Background: Despite evidence of a decline in both incidence and prevalence of colorectal cancer nationwide, it remains the second most commonly diagnosed cancer and the third highest cause of mortality among Asian Americans, including Korean Americans. This community-based and theoretically guided study evaluated a culturally appropriate intervention program that included a bilingual cancer educational program among Korean Americans including information on CRC risks, counseling to address psychosocial and access barriers, and patient navigation assistance. Methods: A two-group quasi-experimental design with baseline and post-intervention assessment and a 12-month follow-up on screening was used in the study. Korean Americans (N = 167) were enrolled from six Korean churches. The intervention group received culturally appropriate intervention program addressing accessibility and psychosocial barriers, and navigation assistance for screening. The control group received general health education that included cancer-related health issues and screening. Results: There was a significant difference (p < 0.05) between the post-intervention and control groups in awareness of CRC risk factors. There was also a significant improvement in the pre–post across HBM measures in the intervention group for perceived susceptibility (p < 0.05) and benefits and barriers to screening (p < 0.001). At baseline, 13% of participants in the intervention group and 10% in control group reported having had a CRC cancer screening test in the previous year. At the 12-month post-intervention follow-up, 77.4% of participants in the intervention group had obtained screening compared to 10.8% in the control group. Conclusion: While health disparities result from numerous factors, a culturally appropriate and church-based intervention can be highly effective in increasing knowledge of and access to, and in reducing barriers to CRC screening among underserved Koreans.     

No association between garlic intake and risk of colorectal cancer

BackgroundAlthough experimental studies suggested beneficial role of garlic intake on colorectal carcinogenesis, limited prospective cohort studies have evaluated garlic intake in relation to colorectal cancer (CRC) incidence.MethodsWe followed 76,208 women in the Nurses’ Health Study and 45,592 men in the Health Professionals Follow-up Study for up to 24 years and examined garlic intake and garlic supplement use in relation to CRC risk. Information on garlic intake and supplement use was assessed using a validated food frequency questionnaire and a Cox proportional hazard regression model was used to estimate the multivariable hazard ratio (MV-HR) and 95% confidence intervals (95% CIs).ResultsWe documented 2368 (1339 women and 1029 men) incident CRC cases and found no association between garlic intake and CRC risk; the MV-HRs (95% CIs) associated with garlic (1 clove or 4 shakes per serving) intake ≥1/day compared with <1/month were 1.21 (0.94–1.57; p-trend = 0.14) for women and 1.00 (0.71–1.42; p-trend = 0.89) for men. The MV-HRs (95% CIs) of CRC for garlic supplement use, which was used in 6% of the participants in each study, were 0.72 (0.48–1.07) for women and 1.22 (0.83–1.78) for men.ConclusionOur prospective data do not support an important role of garlic intake or garlic supplement use in colorectal carcinogenesis.     

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer

Aim: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. Methods: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p = 0.006), the grade (p = 0.002), carcinoma in situ (p = 0.01), the recurrence (p = 0.009), the progression (p = 0.009), and the death (p = 0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p = 0.008) and OS (p = 0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p = 0.03) and OS (p = 0.03). Conclusion: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.     

Aluminum chloride impacts dentate gyrus structure in male adult albino Wistar rats

To get better insights into the aluminum neurotoxicity, rats were treated with AlCl₃ for increasing doses and periods. Body and brain weights, plasma and brain AlCl₃ levels were assayed. Light microscopy observation of brain was performed. AlCl₃ exposure showed a significant decrease (p < 0.05) on body and brain weight with the highest dose at 18 months. Statistical analysis confirms no significant interaction during 6 months (ρ = 0.357; p > 0.05) while, significant correlation was observed during 12 (ρ = 0.836; p < 0.001) and 18 months (ρ = 0.769; p < 0.001) between body and brain weight. Plasma and brain AlCl₃ concentration increased significantly (p < 0.05) with dose and period dependent manner. Statistical analysis confirms significant interaction between brain concentrations of AlCl₃ and administrated doses during 6 (ρ = 0.969; p < 0.001), 12 (ρ = 0.971; p < 0.001) and 18 months (ρ = 0.965; p < 0.001). Similar relation was established between plasma AlCl₃ concentration and administrated doses during 6 (ρ = 0.970; p < 0.001), 12 (ρ = 0.971; p < 0.001) and 18 months (ρ = 0.964; p < 0.001). Significant relation was confirmed between plasma and brain AlCl₃ concentration during 6 (ρ = 0.926; p < 0.001), 12 (ρ = 0.983; p < 0.001) and 18 months (ρ = 0.906; p < 0.001). Morphological alterations mainly targeted the subgranular layer with modulation of the dentate gyrus appearance. This study highlights the toxic effect of AlCl₃ on the brain which may affects learning and memory and seems to be different according to dose and duration of exposure.     

Measurement of DNA damage in peripheral blood by the γ-H2AX assay as predictor of colorectal cancer risk

The detection of γ-H2AX focus is one of the most sensitive ways to monitor DNA double-strand breaks (DSBs). Although changes in γ-H2AX activity have been studied in tumor cells in colorectal cancer (CRC), changes in peripheral blood lymphocytes (PBLs) have not been examined previously. We hypothesize that higher levels of irradiation-induced γ-H2AX in PBLs may be associated with an elevated risk of colorectal cancer (CRC). In a case-control study, the baseline and ionizing radiation (IR)-induced γ-H2AX levels in PBLs from frequency-matched 320 untreated CRC patients and 320 controls were detected by a laser scanning cytometer-based immunocytochemical method. We used unconditional multivariable logistic regression to evaluate CRC risk by using the ratio of IR-induced γ-H2AX to the baseline levels with adjustment of age, sex and smoking status. We found CRC cases had significantly higher γ-H2AX ratio (1.5 vs. 1.41, P < 0.0001) compared with controls. When using the median γ-H2AX ratio of controls as a cutoff point, we found higher γ-H2AX ratio was significantly associated with an increased risk of CRC (OR = 6.72, 95% CI = 4.54–9.94). Quartile analyses also showed significant dose–response relationship between higher γ-H2AX ratio and increased risk of CRC (P for trend < 0.0001). Age, sex, BMI and smoking status also influenced the association of γ-H2AX ratio with CRC risk; however, no interactions with γ-H2AX ratio were observed. These results support the premise that DSBs in peripheral blood as measured by γ-H2AX level might represent an intermediate phenotype to assess the risk of CRC. Future prospective studies are necessary to confirm our findings in independent populations.     

Obesity,physical activity and cancer risks: Results from the Cancer,Lifestyle and Evaluation of Risk Study (CLEAR)

IntroductionPhysical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers.MethodsWe estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression.ResultsFor women, BMI was positively associated with UC risk; specifically, obese women (BMI ≥30 kg/m²) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (<25 kg/m²) (OR = 1.99;CI:1.31–3.03). For men, BMI was also positively associated with the risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR = 1.37;CI:1.11–1.70), 113% (OR = 2.13;CI:1.55–2.91) and 51% (OR = 1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMI<25 kg/m²).Among women, PA was inversely associated with the risks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR = 0.60;CI:0.44–0.84) and UC (OR = 0.47;CI:0.27–0.80). Reduced risks of BC were associated with low (OR = 0.66;CI:0.51–0.86) and moderate (OR = 0.72;CI:0.57–0.91) levels of PA. There was no association between PA levels and cancer risks for men.We found no evidence of an interaction between BMI and PA in the CLEAR study.ConclusionThese findings suggest that PA and obesity are independent cancer risk factors.     

Comparison of quadrant-specific breast cancer incidence trends in the United States and England between 1975 and 2013

BackgroundUK breast cancer incidence rates suggest that upper outer quadrant (UOQ) cancers have risen disproportionately compared with other areas over time. We aimed to provide a comparison of the trend in quadrant-specific breast cancer incidence between the United States (US) and England, and determine whether a disproportionate UOQ increase is present.MethodsSurveillance Epidemiology and End Results (SEER) cancer registry data were obtained on 630,007 female breast cancers from 1975 to 2013. English cancer registry data were obtained on 1,121,134 female breast cancers from 1979 to 2013. Temporal incidence changes were analysed using negative binomial regression. Interaction terms determined whether incidence changes were similar between sites.ResultsEnglish breast cancer incidence in the UOQ rose significantly from 13% to 28% from 1979 to 2013 whereas no significant increase was observed among SEER data. The significant interaction between quadrant and year of diagnosis (p < 0.001) in both SEER and English data indicates that breast cancer incidence in each quadrant changed at a different rate. Incidence in the UOQ rose disproportionately compared to the nipple (SEER IRR = 0.81, p < 0.001; England IRR = 0.78, p < 0.001) and axillary tail (SEER IRR = 0.87, p = 0.018; England IRR = 0.69, p < 0.001) in both SEER and England. In addition, incidence rose disproportionately in the UOQ compared to non-site-specific tumours in England (Overlapping lesions IRR = 0.81, p = 0.002; NOS IRR = 0.78, p < 0.001). The proportion of non-site-specific tumours was substantially higher in England than SEER throughout the study period (62% in England; 39% in SEER).ConclusionsBreast cancer incidence in the UOQ increased disproportionately compared to non-site-specific tumours in England but not in SEER, likely due to the decrease in non-site-specific tumours observed in England over time. There may be real differences in incidence between the two countries, possibly due to differences in aetiology, but is much more likely to be an artefact of changing data collection methods and improvements in site coding in either country.     

Survivin and its spliced isoform gene expression is associated with proliferation of renal cancer cells and clinical stage of renal cancer

Background: Survivin has been implicated in inhibition of apoptosis. To date, alternatively spliced isoforms, Survivin-2α, -2B, -ΔEx3, -3B, have been described. We assessed the effect of survivin gene expression on the proliferation of renal cancer (RCC) cells, and studied the association of survivin and its spliced isoform gene expression levels with the clinical stage of RCC. Methods: Gene expression of survivin and its spliced isoform in RCC cells, Caki-1, were performed by RT-PCR. We knocked down the gene expression of Survivin using small interfering RNA (siRNA), and assessed the cell proliferation by MTS assay. Next, we quantified the gene expression levels of survivin and its isoform in nephrectomy samples using quantitative real-time PCR. Results: In Caki-1 cells, survivin and survivin-2α, -2B were expressed higher than survivin-ΔEx3. Decrease of Survivin gene expression by transfection of siRNA was accompanied by inhibition of the proliferation of Caki-1 cell with 36% decrease in comparison with negative control transfected cells (p < 0.01). In clinical RCC tissues, survivin expression levels in metastatic stage were significantly higher compared with those in distant metastasis stage (M0:M1 = 1:4.81, p = 0.014); survivin 2B gene expression levels in pT3 tumors were associated significantly higher than those in pT1 (pT1:pT3 = 1:4.50, p = 0.043). No significant differences were found in survivin-2α expression levels and the ratio of survivin-2B/survivin gene expression levels among any clinical stages. Conclusion: We first demonstrated the gene expression of survivin-2α in renal cancer cells, and also showed that survivin and its spliced isoforms had associations with renal cancer cell proliferation and distant metastases.     

TRIM28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer

TRIM28 is a universal corepressor for Kruppel-associated box zinc finger proteins. In this study, we demonstrated the expression of TRIM28 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < 0.001). TRIM28 knockdown resulted in a decrease in cell proliferation in liquid media as well as in soft agar. The proliferation rate was impaired and the cell cycle progression was inhibited after knockdown of TRIM28 in non-small cell lung cancer cell lines PAa and SK-MES-1. We used real-time polymerase chain reaction to detect circulating cancer cells in 138 non-small cell lung cancer patients. The overall positive detection rate was 30.4% (42 of 138) in peripheral blood of NSCLC patients and was 29.9% (29 of 97) in early-stage patients. In a 70-month follow-up study, 20 of 29 patients (69.0%) in TRIM28 positive group had recurrence and/or metastasis, significantly higher (P = 0.004) than in the TRIM28 negative group (25 of 68, 36.8%). In addition, non-small cell lung cancer patients whose circulating cancer cells expressed TRIM28 suffered shorter tumor-specific survival compared with those with absent TRIM28 expression (P < 0.001). Results of our study showed that TRIM28 provides a survival advantage to lung cancer cells and may be a new marker to predict metastasis and prognosis in early-stage non-small cell lung cancer patients.     

Associations of body mass index with cancer incidence among populations,genders, and menopausal status: A systematic review and meta-analysis

In order to further reveal the differences of association between body mass index (BMI) and cancer incidence across populations, genders, and menopausal status, we performed comprehensive meta-analysis with eligible citations. The risk ratio (RR) of incidence at 10 different cancer sites (per 5 kg/m² increase in BMI) were quantified separately by employing generalized least-squares to estimate trends, and combined by meta-analyses. We observed significantly stronger association between increased BMI and breast cancer incidence in the Asia⿿Pacific group (RR 1.18:1.11⿿1.26) than in European⿿Australian (1.05:1.00⿿1.09) and North-American group (1.06:1.03⿿1.08) (meta-regression p < 0.05). No association between increased BMI and pancreatic cancer incidence (0.94:0.71⿿1.24) was shown in the Asia⿿Pacific group (meta-regression p < 0.05), whereas positive associations were found in other two groups. A significantly higher RR in men was found for colorectal cancer in comparison with women (meta-regression p < 0.05). Compared with postmenopausal women, premenopausal women displayed significantly higher RR for ovarian cancer (pre- vs. post- = 1.10 vs. 1.01, meta-regression p < 0.05), but lower RR for breast cancer (pre- vs. post- = 0.99 vs. 1.11, meta-regression p < 0.0001). Our results indicate that overweight or obesity is a strong risk factor of cancer incidence at several cancer sites. Genders, populations, and menopausal status are important factors effecting the association between obesity and cancer incidence for certain cancer types.     

Luminal (Her2 negative) prognostic index and survival of breast cancer patients

PurposeThe group of luminal (Her2 negative) is distinguished from other subtypes of breast cancer. We aimed to produce a prognostic index specific for luminal (Her2 negative) subtype breast cancer that could assist clinical treatment.MethodsThe test set comprised 406 consecutive luminal (Her2 negative) breast cancer patients. The relationship of 11 clinicopathologic factors including survivin with the 5-year disease-free survival was analyzed.ResultsIn univariate analysis, TNM stage, surgery, tumor size, lymph node involvement, and survivin expression were prognostic factors. In multivariate analysis, tumor size [HR (95% CI): 1.98 (1.12–3.49), p = 0.019], the number of lymph node metastasis [HR (95% CI): 1.75 (1.33–2.29), p < 0.0001] and the expression of progesterone receptor [HR (95% CI): 0.58 (0.36–0.95), p = 0.029] can independently predict prognosis. Prognostic index (PI) was calculated as 0.68 × tumor size + 0.56 × the number of lymph node metastasis − 0.54 × PR. According to the PI, patients were categorized into three groups: low, middle, and high risk group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%, respectively (P < 0.001). In the validation set, the luminal prognostic index (LPI) remained significant.ConclusionThe LPI may be a useful tool for evaluating the outcome of patients with luminal (Her-2 negative) breast cancer.