Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

Objective

To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG).

Methods

This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively.

Results

Thirteen studies—seven case-control studies and six population-based cohort studies—were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25–1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17–1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06–1.74).

Conclusions

Individuals with DM have an increased risk of developing POAG.     

The Effects of Postmenopausal Hormone Use on Cataract: A Meta-Analysis

Background

Cataract is the leading cause of blindness worldwide. Many observational studies assessed the relationship between postmenopausal hormone replacement therapy (HRT) and risk of cataract development, but the reported results were controversial. The aim of present meta-analysis was to evaluate the association of postmenopausal hormone replacement therapy with risk of cataract development.

Methods

The eligible observational studies, including cross-sectional, case–control and cohort studies, were identified by searching PubMed and Embase during March of 2013. Either a fixed- or a random-effects model was used to calculate the pooled odds ratio (OR) with its 95% confidence interval (95%CI). Subgroup analysis on cataract types was performed.

Results

A total of four cohort and five case-control or cross-sectional studies were finally included into this meta-analysis. Overall, a significant decreased risk of developing any type of cataract was found in ever HRT group as compared with non-HRT group among cohort studies (OR 0.83; 95%CI: 0.71,0.97) and case-control or cross-sectional studies (OR 0.74; 95%CI: 0.59,0.93). Subgroup analysis on cataract types determined that the significantly decreased risk of nuclear cataract in current HRT group (OR 0.72; 95%CI: 0.61,0.85) and also a critically reduced risk of nuclear cataract in ever HRT group (OR 0.80; 95% CI: 0.64,1.01) were found among case-control or cross-sectional studies, as compared with non-HRT group. No association of HRT with risk of cortical and posterior subcapsular cataract was observed.

Conclusions

The results of present meta-analysis indicate that postmenopausal hormone use may play a protective role in cataract development.     

Hypertension and Risk of Cataract: A Meta-Analysis

Background

Cataract is the major cause of blindness across the world. Many epidemiologic studies indicated that hypertension might play an important role in the development of cataract, while others not. We therefore conducted this meta-analysis to determine the relationship between risk of cataract and hypertension.

Methods

Retrieved studies on the association of hypertension with cataract risk were collected from PubMed, Web of Science and the Cochrane Library during June 2014 and were included into the final analysis according to the definite inclusion criteria. Odds ratio (OR) or risk ratio (RR) were pooled with 95% confidence interval (CI) to evaluate the relationship between hypertension and cataract risk. Subgroup analyses were carried out on the basis of cataract type, race and whether studies were adjusted for main components of metabolic syndrome (MS).

Results

The final meta-analysis included 25 studies (9 cohort, 5 case-control and 11 cross-sectional) from 23 articles. The pooled results showed that cataract risk in populations with hypertension significantly increased among cohort studies (RR 1.08; 95% CI: 1.05–1.12) and case-control or cross-sectional studies (OR 1.28; 95% CI: 1.12–1.45). This association was proved to be true among both Mongolians and Caucasians, and the significance was not altered by the adjustment of main components of MS. Subgroup analysis on cataract types indicated that an increased incidence of posterior subcapsular cataract (PSC) resulted among cohort studies (RR 1.22; 95% CI: 1.03–1.46) and cross-sectional/case-control studies (OR 1.23; 95% CI: 1.09–1.39). No association of hypertension with risk of nuclear cataract was found.

Conclusions

The present meta-analysis suggests that hypertension increases the risk of cataract, especially PSC. Further efforts should be made to explore the potential biological mechanisms.     

Diabetes Mellitus and Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.     

Association between Benzodiazepine Use and Dementia: A Meta-Analysis

BackgroundThe association between long-term benzodiazepine use and risk of dementia remains controversial. Therefore, current study aimed to quantify this association, and to explore a potential dose–response pattern.MethodsWe searched PubMed, Embase and the Cochrane Library through August 17, 2014. We included nested case-control or prospective cohort studies that provided risk estimates on the association of benzodiazepine use with risk of dementia, and a clear definition of status of benzodiazepine use. Overall effect size was calculated using a random-effects model.FindingsSix studies were eligible for inclusion, involving 11,891 dementia cases and 45,391 participants. Compared with never users, pooled adjusted risk ratios (RRs) for dementia were 1.49 (95% confidence interval (CI) 1.30–1.72) for ever users, 1.55 (95% CI 1.31–1.83) for recent users, and 1.55 (95% CI 1.17–2.03) for past users. The risk of dementia increased by 22% for every additional 20 defined daily dose per year (RR, 1.22, 95%CI 1.18–1.25). When we restricted our meta-analyses to unadjusted RRs, all initial significant associations persisted.ConclusionsLong-term benzodiazepine users have an increased risk of dementia compared with never users. However, findings from our study should be treated with caution due to limited studies and potential reverse causation. Large prospective cohort studies with long follow-up duration are warranted to confirm these findings.     

Systemic Hypertension as a Risk Factor for Open-Angle Glaucoma: A Meta-Analysis of Population-Based Studies

Background/Aims

Systemic hypertension is thought to increase the risk for developing open-angle glaucoma (OAG) through several mechanisms. However, previous epidemiological studies have shown conflicting results regarding this potential association. We systematically evaluated this issue by conducting a meta-analysis of population-based studies.

Methods

A comprehensive search for articles published before 31 March 2014 was performed using PubMed, Embase, and reference lists. The pooled odds ratio (OR) was calculated using the fixed- and random-effects models, and meta-regression was performed according to age. Subgroup analyses were also conducted, and publication bias was assessed using a funnel plot and Egger’s regression test.

Results

This meta-analysis included 16 studies involving 60,084 individuals, with substantial homogeneity among the studies. The pooled OR for OAG was 1.22 (95% confidence interval, CI: 1.09–1.36) using the fixed-effects model and 1.22 (95% CI: 1.08–1.37) using the random-effects model in all included studies. For subgroup analyses, the pooled OR for high-tension glaucoma (HTG) was higher than that for normal-tension glaucoma (NTG) (OR = 1.92 and 0.94, respectively). No significant difference was detected between Asian and Western populations, and no publication bias was detected in either analysis.

Conclusions

Systemic hypertension increases the risk for developing OAG, especially in those with HTG.     

Aspirin Use and Risk of Age-Related Macular Degeneration: A Meta-Analysis

Background

Age-related macular degeneration (AMD) is the main cause of blindness and the curative options are limited. The objective of this meta-analysis was to determine the association between aspirin use and risk of AMD.

Methods

A comprehensive literature search was performed in PubMed, Embase, Web of Science, and reference lists. A meta-analysis was performed by STATA software.

Results

Ten studies involving 171729 individuals examining the association between aspirin use and risk of AMD were included. Among the included studies, 2 were randomized-controlled trials (RCTs), 4 were case-control studies and 4 were cohort studies. The relative risks (RRs) were pooled using a random-effects model. Relative risks with 95% confidence intervals (CIs) of aspirin use as a risk for AMD. The pooled RR of 10 included studies between the use of aspirin and risk of AMD was 1.09 (95% CI, 0.96–1.24). The same result was detected in early and late stage AMD subgroup analysis. In the subgroup analyses, the pooled RR of RCTs, case-control studies and cohort studies were 0.81 (95% CI, 0.64–1.02), 1.02 (95% CI, 0.92–1.14) and 1.08 (95% CI, 0.91–1.28), respectively.

Conclusions

The use of aspirin was not associated with the risk of AMD.     

Hepatitis C Virus Infection and Risk of Stroke: A Systematic Review and Meta-Analysis

Background/Aims

Several studies analyzed the association between hepatitis C virus (HCV) infection and the risk of stroke or cerebrovascular death, but their findings were inconsistent. Up to date, no systematic review about the association between HCV infection and stroke was performed. We conducted a meta-analysis to examine whether HCV infection dose increase stroke risk in comparison to the population without HCV infection.

Methods

We followed standard guidelines for performance of meta-analysis. Two independent investigators identified eligible studies through structured keyword searches in several databases. Random-effects and fixed-effects models were used to synthesize the data. Heterogeneity between studies and publication bias were also accessed.

Results

Combining the data from the eligible studies, we calculated the pooled multi-factor adjusted Odds Ratio (OR) with 95% confidence interval (CI). Upon the heterogeneity found between studies, the result was 1.58 (0.86, 2.30) by random-effects model. However, after omitting the study which induced heterogeneity, the pooled OR with 95% CI was 1.97 (1.64, 2.30).

Conclusions

This meta-analysis suggested that HCV infection increased the risk of stroke. More prospective cohort studies will be needed to confirm this association with underlying biological mechanisms in the future.     

The Effect of HIV-Hepatitis C Co-Infection on Bone Mineral Density and Fracture: A Meta-Analysis

Objective

There is a variable body of evidence on adverse bone outcomes in HIV patients co-infected with hepatitis C virus (HCV). We examined the association of HIV/HCV co-infection on osteoporosis or osteopenia (reduced bone mineral density; BMD) and fracture.

Design

Systematic review and random effects meta-analyses.

Methods

A systematic literature search was conducted for articles published in English up to 1 April 2013. All studies reporting either BMD (g/cm², or as a T-score) or incident fractures in HIV/HCV co-infected patients compared to either HIV mono-infected or HIV/HCV uninfected/seronegative controls were included. Random effects meta-analyses estimated the pooled odds ratio (OR) and the relative risk (RR) and associated 95% confidence intervals (CI).

Results

Thirteen eligible publications (BMD N = 6; Fracture = 7) of 2,064 identified were included with a total of 427,352 subjects. No publications reported data on HCV mono-infected controls. Meta-analysis of cross-sectional studies confirmed that low bone mineral density was increasingly prevalent among co-infected patients compared to HIV mono-infected controls (pooled OR 1.98, 95% CI 1.18, 3.31) but not those uninfected (pooled OR 1.47, 95% CI 0.78, 2.78). Significant association between co-infection and fracture was found compared to HIV mono-infected from cohort and case-control studies (pooled RR 1.57, 95% CI 1.33, 1.86) and compared to HIV/HCV uninfected from cohort (pooled RR 2.46, 95% CI 1.03, 3.88) and cross-sectional studies (pooled OR 2.30, 95% CI 2.09, 2.23).

Conclusions

The associations of co-infection with prevalent low BMD and risk of fracture are confirmed in this meta-analysis. Although the mechanisms of HIV/HCV co-infection’s effect on BMD and fracture are not well understood, there is evidence to suggest that adverse outcomes among HIV/HCV co-infected patients are substantial.     

Bisphosphonate Use and Risk of Implant Revision after Total Hip/Knee Arthroplasty: A Meta-Analysis of Observational Studies

ObjectiveSeveral studies investigated the association between bisphosphonate use and the risk of implant revision after total hip or knee arthroplasty (THA or TKA); However, the findings were inconsistent. We performed this meta-analysis to evaluate the overall relative risk of such an event.MethodsWe searched the PubMed, EMBASE and Cochrane library databases to identify relevant publications on April 22, 2015. To calculate the pooled risk ratios (RRs) with 95% confidential intervals (CIs), a fixed- or random-effects model was applied based on the heterogeneity across studies.ResultsThree cohort studies and one case-control study were included in this meta-analysis. Compared with the bisphosphonate nonusers, the patients who used bisphosphonates for a long period of time had a significantly decreased risk of implant revision after THA/TKA (summary adjusted RR = 0.48, 95% CI: 0.38–0.61), and the summary adjusted RRs for the users who underwent THA and those who underwent TKA were 0.47 (95% CI: 0.36–0.61) and 0.45 (95% CI: 0.21–0.95), respectively.ConclusionsLong-term use of bisphosphonates is correlated with a significantly decreased risk of implant revision after THA/TKA. However, due to limited number of the included studies, the findings of the present study should be treated with caution. More well-designed studies are required to further confirm our findings.     

Obesity and Risk of Hip Fracture in Adults: A Meta-Analysis of Prospective Cohort Studies

Background

Many observational studies assessed the association between obesity and risk of hip fracture in adults, but reported controversial results. Our goal was to evaluate the association between obesity and risk of hip fracture in adults by conducting a meta-analysis of prospective cohort studies.

Methods

Three databases, PubMed, Embase and Web of Science, were searched through May 2012 to identify eligible cohort studies. Either a fixed- or a random-effects model was used to calculate the pooled relative risk (RR) with its 95% confidence interval (95%CI).

Results

Fifteen prospective cohort studies involving a total 3,126,313 participants were finally included into this meta-analysis. Overall, adults with obesity compared with the normal weight group had a significantly decreased risk of hip fracture (RR: 0.66, 95% CI 0.57 to 0.77, P<0.001). Meta-analyses by the adjusted status of RRs also suggested adults with obesity compared with the reference group had a significantly decreased risk of hip fracture (adjusted RR: 0.48, 95% CI 0.39 to 0.58, P<0.001; unadjusted RR: 0.66, 95% CI 0.56 to 0.78, P<0.001). Subgroup analyses by gender suggested individuals with obesity had a significantly decreased risk for developing hip fracture compared with the reference group in both men (RR 0.54, 95% CI 0.48 to 0.60, P<0.001) and women (RR 0.70, 95% CI 0.58 to 0.84, P<0.001). No evidence of publication bias was observed in this meta-analysis.

Conclusions

This meta-analysis of prospective cohort studies suggests that obesity significantly decreases the risk of hip fracture in adults, and obesity is probably a protective factor of hip fracture in adults.     

Alcohol-Related Risk of Suicidal Ideation,Suicide Attempt,and Completed Suicide: A Meta-Analysis

BackgroundSeveral original studies have investigated the effect of alcohol use disorder (AUD) on suicidal thought and behavior, but there are serious discrepancies across the studies. Thus, a systematic assessment of the association between AUD and suicide is required.MethodsWe searched PubMed, Web of Science, and Scopus until February 2015. We also searched the Psycinfo web site and journals and contacted authors. We included observational (cohort, case-control, and cross-sectional) studies addressing the association between AUD and suicide. The exposure of interest was AUD. The primary outcomes were suicidal ideation, suicide attempt, and completed suicide. We assessed heterogeneity using Q-test and I² statistic. We explored publication bias using the Egger''s and Begg''s tests and funnel plot. We meta-analyzed the data with the random-effects models. For each outcome we calculated the overall odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI).ResultsWe included 31 out of 8548 retrieved studies, with 420,732 participants. There was a significant association between AUD and suicidal ideation (OR=1.86; 95% CI: 1.38, 2.35), suicide attempt (OR=3.13; 95% CI: 2.45, 3.81); and completed suicide (OR=2.59; 95% CI: 1.95, 3.23 and RR=1.74; 95% CI: 1.26, 2.21). There was a significant heterogeneity among the studies, but little concern to the presence of publication bias.ConclusionsThere is sufficient evidence that AUD significantly increases the risk of suicidal ideation, suicide attempt, and completed suicide. Therefore, AUD can be considered an important predictor of suicide and a great source of premature death.     

Fish Intake and Risk of Liver Cancer: A Meta-Analysis

Background

Increasing laboratory findings indicate that n-3 fatty acids, mainly derived from fish, inhibit cancer development and progression, but results from epidemiologic studies have been inconsistent and inconclusive.

Objective

To evaluate the association of fish intake with risk of liver cancer by conducting a meta-analysis.

Methods

Published case-control/cohort studies that evaluated the relationship between total fish intake and risk of liver cancer were found on PubMed and EMBASE. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were obtained with the random-effects model.

Results

Five retrospective case-control studies and 5 prospective cohort studies were included in the final analysis, involving a total of 3 624 liver cancer cases. Comparing the highest with the lowest category of total fish intake, the pooled RRs of liver cancer were 0.79 (95% CI, 0.59-1.06) for case-control studies, 0.82 (95% CI, 0.70-0.96) for cohort studies and 0.82 (95% CI, 0.71-0.94) for all studies combined. The protective effects of total fish intake against liver cancer were confirmed by stratified and sensitivity analyses. In addition, an increase in fish intake of 1 serving/week was estimated to be significantly associated with 6% lower risk of liver cancer (RR = 0.94, 95% CI, 0.91-0.98).

Conclusions

Findings from this meta-analysis suggest that a higher fish intake is associated with reduced risk of liver cancer.     

Parity and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis

BackgroundClinical breast cancer subtypes are categorized basing on the expression of hormone receptors and overexpression of the human epidermal growth factor receptor 2 (HER2). It is still unclear whether parity impact the risk of different breast cancer subtypes.MethodsWe searched eight mainstream databases for published epidemiologic studies that assessed the relationship between parity and risk of breast cancer subtypes up to January 12, 2021. Parity number were unified into nulliparity and ever parity. The random-effects or fixed-effect models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) among different subtypes. Restricted cubic spline analysis with four knots was applied to determine the relationship of parity number and risk of breast cancer subtypes.ResultsWe pooled sixteen case-control and four cohort studies, and performed an analysis including 7795 luminal A, 3576 luminal B, 1794 HER2-overexpressing, and 5192 triple-negative breast cancer cases among 1135131 participants. The combined ORs for ever parity versus nulliparity indicated a 34% reduction in luminal A risk (OR=0.66, 95% CI: 0.56–0.78), and a 29% reduction in luminal B risk (OR=0.71, 95% CI: 0.63–0.81), there was no significant association in HER2-overexpressing or TNBC risk. In the dose-response analysis, we observed a potentially non-linear and gradually increasing protective relationship between the number of parity and luminal breast cancer risk.ConclusionsThe effect of parity on breast cancer seems to vary among breast tumor subtypes, and it plays a protective role in luminal breast cancer.     

Statins and the Risk of Lung Cancer: A Meta-Analysis

Purpose

Several epidemiologic studies have evaluated the association between statins and lung cancer risk, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. We conducted a meta-analysis of all relevant studies to examine this association.

Methods

A systematic literature search up to March 2012 was performed in PubMed database. Study-specific risk estimates were pooled using a random-effects model.

Results

Nineteen studies (5 RCTs and 14 observational studies) involving 38,013 lung cancer cases contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of lung cancer either among RCTs (relative risk [RR] 0.91, 95% confidence interval [CI] 0.76–1.09), among cohort studies (RR 0.94, 95% CI 0.82–1.07), or among case-control studies (RR 0.82, 95% CI 0.57–1.16). Low evidence of publication bias was found. However, statistically significant heterogeneity was found among cohort studies and among case-control studies. After excluding the studies contributing most to the heterogeneity, summary estimates were essentially unchanged.

Conclusion

The results of our meta-analysis suggest that there is no association between statin use and the risk of lung cancer.     

Vitamin C Intake and Pancreatic Cancer Risk: A Meta-Analysis of Published Case-Control and Cohort Studies

Background

Observational studies inconsistently reported the relationship between vitamin C intake and risk of pancreatic cancer. We conducted a meta-analysis of published case-control and cohort studies to quantify the association.

Methods

Potentially eligible studies were found on PubMed and EMBASE databases through May 31, 2015. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity.

Results

Our final analyses included 20 observational studies comprising nearly 5 thousand cases of pancreatic cancer. When comparing the highest with the lowest categories of vitamin C intake, the summary odds ratio/relative risk for case-control studies (14 studies), cohort studies (6 studies) and all studies combined was 0.58 (95% CI: 0.52–0.66), 0.93 (95% CI: 0.78–1.11) and 0.66 (95% CI: 0.58–0.75), respectively. The difference in the findings between case-control and cohort studies was statistically significant (P < .001). Possible publication bias was shown in the meta-analysis of case-control studies.

Conclusion

There is insufficient evidence to conclude any relationship between vitamin C intake and risk of pancreatic cancer. The strong inverse association observed in case-control studies may be affected by biases (eg, recall and selection biases) that particularly affect case-control studies and/or potential publication bias. Future prospective studies of vitamin C intake and pancreatic cancer are needed.     

Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

Background

Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk.

Methods

Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model.

Results

Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I² = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I² = 0%; highest versus lowest quantity of intake).

Conclusions

This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.     

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study

BackgroundThere is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders.MethodsTwenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type.ResultsWe observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10–19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12–15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90).ConclusionsWhether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.     

The Aetiological Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma: A Meta-Analysis

Background

The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC.

Methods

Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR).

Results

From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91).

Conclusions

Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.     

A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer

BackgroundSingle nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results.MethodsWe pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified.ResultsThree SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555–0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730–0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037–2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations.ConclusionRs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.