Cardiac glycosides and breast cancer risk: A systematic review and meta‐analysis of observational studies

Cardiac glycosides are phytoestrogens and have been linked to the risk of estrogen sensitive cancers such as uterus cancer. However, the association between use of cardiac glycosides and risk of breast cancer remains unclear. We investigated the association between cardiac glycosides use and the risk of breast cancer by systematically reviewing the published literature and performing meta‐analyses. A comprehensive literature search was performed using MEDLINE, EMBASE, Web of Science and SCOPUS to identify all relevant articles published up to November 2015. Risk estimates, and accompanying standard errors, for the association between cardiac glycoside use and breast cancer were extracted from identified studies. Meta‐analysis models were used to calculate a combined hazard ratio (HR), and 95% confidence interval (CI), and to investigate heterogeneity between studies. In total, nine studies were identified investigating cardiac glycosides use and risk of developing breast cancer. Overall, there was evidence to suggest an association between cardiac glycosides use and breast cancer risk (HR = 1.34; 95% CI 1.25, 1.44; p < 0.001) with little variation in the association between studies (I² = 16%, p for heterogeneity = 0.30). Results were little altered when analysis was restricted to studies with high quality scores or cohort studies. Overall, there was a 34% increase in breast risk with use of cardiac glycosides but it is unclear whether this association reflects confounding or is causal. Further observational studies are required to examine this association particularly for estrogen receptor positive breast cancer and to explore the role of potential confounding variables.     

Sentinel node biopsy performance after neoadjuvant chemotherapy in locally advanced breast cancer: A systematic review and meta‐analysis

The use of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is debated. Our aim was to quantitatively review the available evidence on the performance of SNB after NAC in patients with locally advanced breast cancer. We performed a systematic review (by searching the PubMed, Cochrane and Scopus databases) and random effects meta‐analysis to investigate on the feasibility and accuracy of SNB in these patients. The two outcomes of interest were the sentinel node identification rate (SIR) and the false negative rate (FNR). Sensitivity analysis and meta‐regression were used to investigate the potential sources of between‐study heterogeneity. We retrieved 72 eligible studies enrolling 7,451 patients. Upon meta‐analysis, summary SIR resulted 89.6% [95% confidence interval (CI): 87.8–91.2; heterogeneity I²: 76.9%], which poorly compares with the 95% SIR observed in some recent series of early breast cancer. The summary FNR resulted 14.2% (CI: 12.5–16.0; heterogeneity I²: 29.1%), which was significantly higher than the 8–10% reference value. Considering an average post‐NAC lymph node positivity rate of 50%, the downstaging due to false negative SNB would occur in 7/100 patients (with an excess error rate of 2–3/100 as compared to the early‐stage setting). No plausible source of between‐study heterogeneity was found. Based on the largest series of studies ever meta‐analyzed, our findings highlight the limits of SNB performance in this population, where the impact of SNB on patient survival is still to be defined.     

Sleep duration and breast cancer risk: A meta‐analysis of observational studies

Studies on the association of short or long sleep duration with breast cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta‐analysis based on the evidence from observational studies. In April 2013, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of sleep duration on breast cancer incidence. The odds ratio (OR) was used to measure any such association in a random‐effects model. The analysis was further stratified by confounding factors that could bias the results. A total of six studies (two case–control and four cohort studies) involving 159,837 individuals were included in our meta‐analysis. Our study did not show an association between either short or long sleep duration and breast cancer risk (short sleep duration data: pooled OR = 1.01, 95% confidence interval (CI) = 0.90–1.14, p = 0.853; long sleep duration data: pooled OR = 0.95, 95% CI = 0.86–1.04, p = 0.251). Moreover, we did not identify any statistically significant association between sleep duration and breast cancer risk in all the subgroup analyses. In conclusion, our findings indicate that sleep duration has no effect on breast cancer risk.     

Cigarette smoking and colorectal cancer incidence and mortality: Systematic review and meta‐analysis

The association between cigarette smoking and colorectal cancer (CRC) has been controversial. To synthesize the available data, we conducted a comprehensive meta‐analysis of all prospective studies. A total of 36 studies were included in our meta‐analysis. We examined the association between smoking and CRC, colon cancer and rectal cancer in terms of incidence and mortality. Separate analyses were conducted for smoking status, daily cigarette consumption, duration, pack‐years and age of initiation. Relative to nonsmokers, current and former smokers had a significantly increased risk of CRC incidence and mortality, respectively. When CRC data were combined with colon/rectal cancer data, current smokers had a significantly increased risk of CRC incidence. All 4 dose–response variables examined—daily cigarette consumption (RR = 1.38 for an increase of 40 cigarettes/day), duration (RR = 1.20 for an increase of 40 years of duration), pack‐years (RR = 1.51 for an increase of 60 pack‐years) and age of initiation (RR = 0.96 for a delay of 10 years in smoking initiation)—were significantly associated with CRC incidence (all p‐values < 0.0001). The relationship between duration of smoking and rectal cancer incidence was also significant. Among the subset of studies that distinguished cancer by site, a higher risk was seen for rectal cancer than for colon cancer for all analyses. Among prospective studies, a consistent association exists between smoking and CRC. The association is stronger for rectal cancer than for colon cancer in the subset of studies that differentiated cancer by site. © 2008 Wiley‐Liss, Inc.     

Associations between statin use and non‐Hodgkin lymphoma (NHL) risk and survival: a meta‐analysis

Evidence on the effect of statin use on non‐Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta‐analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau‐squared and the I‐squared (I²) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69–0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31–0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99–1.06) or event‐free survival (PHR = 0.99, 95% CI 0.87–1.12) in diffuse large B‐cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Adherence to Mediterranean diet and risk of cancer: A systematic review and meta‐analysis of observational studies

The aim of this research study was to meta‐analyze the effects of adherence to Mediterranean diet (MD) on overall cancer risk, and different cancer types. Literature search was performed using the electronic databases MEDLINE, SCOPUS and EMBASE until January 10, 2014. Inclusion criteria were cohort or case–control studies. Study specific risk ratios (RRs) were pooled using a random effect model by the Cochrane software package Review Manager 5.2. Twenty‐one cohort studies including 1,368,736 subjects and 12 case–control studies with 62,725 subjects met the objectives and were enclosed for meta‐analyses. The highest adherence to MD category resulted in a significantly risk reduction for overall cancer mortality/incidence (cohort; RR: 0.90, 95% CI 0.86–0.95, p < 0.0001; I² = 55%), colorectal (cohort/case–control; RR: 0.86, 95% CI 0.80–0.93, p < 0.0001; I² = 62%], prostate (cohort/case–control; RR: 0.96, 95% CI 0.92–0.99, p = 0.03; I² = 0%) and aerodigestive cancer (cohort/case–control; RR: 0.44, 95% CI 0.26–0.77, p = 0.003; I² = 83%). Nonsignificant changes could be observed for breast cancer, gastric cancer and pancreatic cancer. The Egger regression tests provided limited evidence of substantial publication bias. High adherence to a MD is associated with a significant reduction in the risk of overall cancer mortality (10%), colorectal cancer (14%), prostate cancer (4%) and aerodigestive cancer (56%).     

Effects of statins on cancer mortality and progression: A systematic review and meta‐analysis of 95 cohorts including 1,111,407 individuals

Statins have been implicated in the regulation of cell proliferation, apoptosis and tumor progression in cancer patients and statin use at the time of cancer diagnosis has been reported to be associated with reduced cancer risk and improved survival, irrespective of concomitant anti‐cancer therapy. A systematic literature search of relevant databases through May 2015 was conducted to identify studies assessing the prognostic impact of statin use on prognostic outcomes in cancer patients. Literature search identified 95 cohort studies that met the inclusion criteria. A meta‐analysis of 55 articles showed that statin use was significantly associated with decreased risk of all‐cause mortality (HR 0.70, 95% Cl 0.66 to 0.74) compared with nonusers. The observed pooled estimates were retained for cancer‐specific mortality (HR 0.60, 95% Cl 0.47 to 0.77), progression‐free survival (HR 0.67, 95% Cl 0.56 to 0.81), recurrence‐free survial (HR 0.74, 95% Cl 0.65 to 0.83) and disease‐free survival (HR 0.53, 95% Cl 0.40 to 0.72). These associations almost remained consistent across those outcomes when stratified by publication type, tumour location, study design, sample size, initiation of statins, disease stage, research country, follow‐up duration or research hospital involved. Subgroup analyses according to initiation of statins showed postdiagnosis statin users (HR 0.65, 95% Cl 0.54 to 0.79) gained significantly more recurrence‐free survival benefit than prediagnosis statin users (HR 0.86, 95% Cl 0.77 to 0.96) (p for interaction = 0.018). Statin therapy has potential survival benefit for patients with malignancy. Further large‐scale prospective studies emphasising survival outcomes of individual cancer type are strongly encouraged.     

Prognostic role of neutrophil‐to‐lymphocyte ratio in colorectal cancer: A systematic review and meta‐analysis

The prognostic role of inflammation index like neutrophil‐to‐lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta‐analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression‐free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499–2.193) and PFS (HR: 2.102, 95% CI: 1.554–2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226–2.022) and higher carcino‐embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308–1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.     

Association between human papillomavirus infection and prostate cancer: A global systematic review and meta‐analysis

Although an increasing number of studies have been conducted to evaluate the association between human papillomavirus (HPV) infections and distribution of HPV types worldwide with the risk of prostate cancer (PC), the results remain inadequate. Hence, we investigated the association between HPV infection and PC risk using a meta‐analysis. Relevant studies from January 1990 to December 2016 were searched in PubMed, Web of sciences, and Scopus databases. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to find the association between the prevalence of HPV and prostate cancer risk. To do so, data from 24 studies with 5546 prostate cancer cases were pooled in order to evaluate the heterogeneity of chief parameters including study region, specimen type, HPV DNA source, detection technique, publication calendar period, and Gleason score. All statistical analyses were performed using STATA 11 and MedCalc 13. A significant positive association was found between HPV infection and PC risk (OR = 1.281; P = 0.026). The genotype 16 was more frequently found in patients with PC which significantly increased the cancer risk (OR = 1.60; P < 0.001). Age 65 and older could significantly escalate PC risk (OR = 3.564; P < 0.001). Our results clearly favor the potential pathogenetic link between HPV infection and increased risk of PC affirming that HPV infections could play a part in the risk of PC.     

Hysterectomy and kidney cancer risk: A meta‐analysis

Recent cohort findings suggest that women who underwent a hysterectomy have an elevated relative risk of kidney cancer, although evidence from past studies has been inconsistent. We conducted a systematic review and meta‐analysis of published cohort and case–control studies to summarize the epidemiologic evidence investigating hysterectomy and kidney cancer. Studies published from 1950 through 2012 were identified through a search of PubMed and of references from relevant publications. Meta‐analyses were conducted using random‐effects models to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for hysterectomy, age at hysterectomy (<45, 45+ years) and time since hysterectomy (<10, 10+ years). The SRR for hysterectomy and kidney cancer for all published studies (seven cohort, six case–control) was 1.29 (95% CI, 1.16–1.43), with no evidence of between‐study heterogeneity or publication bias. The summary effect was slightly weaker, although still significant, for cohorts (SRR, 1.26; 95% CI, 1.11–1.42) compared with case–control findings (1.37; 95% CI, 1.09–1.73) and was observed irrespective of age at hysterectomy, time since the procedure and model adjustment for body mass index, smoking status and hypertension. Women undergoing a hysterectomy have an approximate 30% increased relative risk of subsequent kidney cancer. Additional research is needed to elucidate the biological mechanisms underlying this association.     

Circulating insulin‐like growth factor peptides and prostate cancer risk: A systematic review and meta‐analysis

Insulin‐like growth factors (IGF‐I, IGF‐II) and their binding proteins (IGFBP‐1–6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta‐analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta‐analysis were 42 (7,481) IGF‐I; 10 (923) IGF‐II; 3 (485) IGFBP‐1; 5 (577) IGFBP‐2; 29 (6,541) IGFBP‐3 and 11 (3,545) IGF‐1:IGFBP‐3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide were: IGF‐I, OR = 1.21 (1.07, 1.36); IGF‐II, OR = 1.17 (0.93, 1.47); IGFBP‐1, OR = 1.21 (0.62, 2.33); IGFBP‐2, OR = 1.18 (0.90, 1.54); IGFBP‐3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP‐3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I² > 75%), partly explained by study design: the magnitude of associations was smaller in prospective vs. retrospective studies, and for IGFBP‐3, the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF‐I and IGFBP‐3 with prostate cancer were stronger for advanced disease. Our meta‐analysis confirms that raised circulating lGF‐I is positively associated with prostate cancer risk. Associations between IGFBP‐3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF‐II, IGFBP‐1 or IGFBP‐2 in prostate cancer risk. © 2008 Wiley‐Liss, Inc.     

A systematic review and meta‐analysis of exercise interventions for colorectal cancer patients

The aim of this systematic review and meta‐analysis was to investigate the effectiveness of exercise for colorectal cancer patients. Pubmed/Medline, Scopus and the Cochrane Library were searched through December 2012 without language restrictions. Randomised controlled trials (RCTs) comparing exercise interventions to control conditions were analysed when they assessed health‐related quality of life, fatigue, physical fitness, survival and/or tumour‐associated biomarkers in colorectal cancer patients. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Literature search identified 342 non‐duplicate records of which five RCTs with a total of 238 patients were included; three RCTs had low risk of bias. No evidence was found for short‐term effects on quality of life [standardised mean difference (SMD) = 0.18; 95% confidence interval (CI) ?0.39, 0.76; P = 0.53] or fatigue (SMD = 0.18; 95% CI ?0.22, 0.59; P = 0.38). There was strong evidence for short‐term improvements of physical fitness after aerobic exercise compared with controls (SMD = 0.59; 95% CI 0.25, 0.93; P < 0.01). One RCT each assessed immune parameters and oxidative DNA damage. No study reported survival rates or safety data. Given this insufficient evidence and the lack of safety data, no recommendation can be made regarding exercise interventions as a routine intervention for colorectal cancer patients.     

Dietary supplement use and colorectal cancer risk: A systematic review and meta‐analyses of prospective cohort studies

Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta‐analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up to January 2013. Original and peer‐reviewed papers on dietary supplement use and colorectal cancer, colon cancer, or rectal cancer incidence were included. “Use‐no use”(U‐NU), “highest‐lowest”(H‐L) and “dose‐response”(DR) meta‐analyses were performed. Random‐effects models were used to estimate summary estimates. In total, 24 papers were included in the meta‐analyses. We observed inverse associations for colorectal cancer risk and multivitamin (U‐NU: RR = 0.92; 95% CI: 0.87,0.97) and calcium supplements (U‐NU: RR = 0.86; 95% CI: 0.79,0.95; H‐L: RR = 0.80; 95% CI: 0.70,0.92; DR: for an increase of 100 mg/day, RR = 0.96; 95% CI: 0.94,0.99). Inconsistent associations were found for colon cancer risk and supplemental vitamin A and vitamin C, and for colorectal cancer risk and supplemental vitamin D, vitamin E, garlic and folic acid. Meta‐analyses of observational studies suggest a beneficial role for multivitamins and calcium supplements on colorectal cancer risk, while the association with other supplements and colorectal cancer risk is inconsistent. Residual confounding of lifestyle factors might be present. Before recommendations can be made, an extensive assessment of dietary supplement use and a better understanding of underlying mechanisms is needed.