Meat subtypes and their association with colorectal cancer: Systematic review and meta‐analysis

Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.     

Obesity and incidence of lung cancer: A meta‐analysis

To date, the relationship between obesity and the incidence of lung cancer remains unclear and inconclusive. Thus, we conducted a meta‐analysis of published studies to provide a quantitative evaluation of this association. Relevant studies were identified through PubMed and EMBASE databases from 1966 to December 2011, as well as through the reference lists of retrieved articles. A total of 31 articles were included in this meta‐analysis. Overall, excess body weight (body mass index, BMI ≥ 25 kg/m²) was inversely associated with lung cancer incidence (relative risk, RR = 0.79; 95% confidence interval, CI: 0.73–0.85) compared with normal weight (BMI = 18.5‐24.9 kg/m²). The association did not change with stratification by sex, study population, study design, and BMI measurement method. However, when stratified by smoking status, the inverse association between excess body weight and lung cancer incidence in current (RR = 0.63, 95% CI: 0.57–0.70) and former (RR = 0.73, 95% CI: 0.58–0.91) smokers was strengthened. In non‐smokers, the association was also statistically significant (RR = 0.83, 95% CI: 0.70–0.98), although the link was weakened to some extent. The stratified analyses also showed that excess body weight was inversely associated with squamous cell carcinoma (RR = 0.68, 95% CI: 0.58–0.80) and adenocarcinoma (RR = 0.79, 95% CI: 0.65–0.96). No statistically significant link was found between excess body weight and small cell carcinoma (RR = 0.99, 95% CI: 0.66–1.48). The results of this meta‐analysis indicate that overweight and obesity are protective factors against lung cancer, especially in current and former smokers.     

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.     

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.     

Gender differences in colorectal cancer survival: A meta‐analysis

A meta‐analysis was conducted to determine the influence of gender on overall survival (OS) and cancer‐specific survival (CSS) in colorectal cancer patients. Major databases were searched for clinical trials, which compare survival differences between male and female for colorectal cancer patients. A list of these studies and references, published in English and Chinese from 1960 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect, the China National Knowledge Infrastructure (CNKI) and Web of Science. Overall survival and cancer‐specific survival were compared using Review Manager 5.3. Females had significantly better OS (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.85–0.89) and CSS (HR = 0.92; 95% CI = 0.89–0.95) than males after meta‐analysis. These results suggest that gender seems to be a significant factor influencing survival results among colorectal cancer patients.     

Association between adult weight gain and colorectal cancer: A dose–response meta‐analysis of observational studies

This study investigated the association between adult weight gain and risk of colorectal cancer (CRC). Using terms related to weight gain and CRC, we searched PubMed, Embase and Web of Science for relevant studies published before June 2014. Two evaluators independently selected studies according to the selection criteria, and eight studies were included (three case–control and five cohort studies). Summary estimates were obtained using fixed‐ or random‐effects models. The relative risk (RR) of the association between adult weight gain and CRC was 1.25 (95% confidence interval [CI], 1.10–1.43); the RR was 1.30 (95% CI, 1.14–1.49) for colon cancer (CC) and 1.27 (95% CI, 1.02–1.58) for rectal cancer (RC) for the highest versus lowest category. For every 5‐kg increase in adult weight, the risk increased by 5% (RR, 1.05; 95% CI, 1.02–1.09) for CRC, 6% (RR, 1.06; 95% CI, 1.02–1.11) for CC and 6% (RR, 1.06; 95% CI, 1.03–1.08) for RC. The subgroup analyses showed a positive association between adult weight gain and risk of CRC only in men, and the RR was 1.65 (95% CI, 1.42–1.92) for the highest versus lowest category of adult weight gain and 1.10 (95% CI, 1.06–1.15) for a 5‐kg increase in adult weight. In conclusion, there is evidence that adult weight gain is associated with an increased risk of CRC. However, the positive association between adult weight gain and risk of CRC is stronger among men than among women.     

Obstructive sleep apnoea and the incidence and mortality of cancer: a meta‐analysis

As there are conflicting reports regarding the association between obstructive sleep apnoea (OSA) and cancer incidence and mortality, a meta‐analysis was performed to evaluate whether OSA is independently associated with cancer incidence and mortality. Pubmed, EMBASE and Web of Science were searched up until November 2014. Studies that assessed OSA and the future risk of cancer incidence or mortality were included. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated. Subgroup analysis was conducted based on the polysomnographic variable, apnoea–hypopnoea index. Six studies, which involved 114 105 participants, were pooled in this meta‐analysis. Fixed‐effects analysis showed the pooled adjusted HR of cancer incidence as 0.91 (95% CI, 0.74–1.13; P = 0.408) for mild OSA, 1.07 (95% CI, 0.86–1.33; P = 0.552) for moderate OSA and 1.03 (95% CI, 0.85–1.26; P = 0.743) for severe OSA. Random‐effects analysis demonstrated neither mild OSA (adjusted HR, 0.79; 95% CI, 0.46–1.34; P = 0.381), moderate OSA (adjusted HR, 1.92; 95% CI, 0.63–5.88; P = 0.251) nor severe OSA (adjusted HR, 2.09; 95% CI, 0.45–9.81; P = 0.349) correlated with cancer mortality. This meta‐analysis indicates that OSA is not independently associated with cancer incidence and mortality according to currently available data. Additional experimental and human research is required to determine the exact association between OSA and cancer.     

Gamma glutamyltransferase,alanine aminotransferase and risk of cancer: Systematic review and meta‐analysis

The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is uncertain. We conducted a systematic review and meta‐analysis of published prospective observational studies evaluating the associations of baseline levels of GGT and ALT with risk of overall (incidence and/or mortality) and site‐specific cancers. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, reference lists of relevant studies to April 2014 and email contact with investigators. Study specific relative risks (RRs) were meta‐analyzed using random effects models. Fourteen cohort studies with data on 1.79 million participants and 57,534 cancer outcomes were included. Comparing top versus bottom thirds of baseline circulating GGT levels, pooled RRs (95% confidence intervals) were 1.32 (1.15–1.52) for overall cancer, 1.09 (0.95–1.24) for cancers of the breast and female genital organs, 1.09 (1.02–1.16) for cancers of male genital organs, 1.94 (1.35–2.79) for cancers of digestive organs and 1.33 (0.94–1.89) for cancers of respiratory and intrathoracic organs. For ALT, corresponding RRs for overall cancer were 0.96 (0.94–0.99) and 1.65 (1.52–1.79) in European and Asian populations, respectively. There was an increased risk of cancers of the digestive organs 2.44 (1.23–4.84). The pooled RR for overall cancer per 5 U/L increment in GGT levels was 1.04 (1.03–1.05). Available observational data indicate a positive log‐linear association of GGT levels with overall cancer risk. The positive association was generally evident for site‐specific cancers. There are geographical variations in the association of ALT and overall cancer.     

Systematic review and meta‐analysis of acupuncture to reduce cancer‐related pain

We conducted a systematic review and meta‐analysis to evaluate the effects of acupuncture on malignancy‐related, chemotherapy (CT)‐ or radiation therapy (RT)‐induced, surgery‐induced, and hormone therapy (HT)‐induced pain. Randomised controlled trials (RCTs) examining the effects of acupuncture on cancer‐related pain were reached from the EMBASE, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, Airiti library, Taiwan Electrical Periodical Service, Wanfang Data (a Chinese database) and China Knowledge Resource Integrated Database from inception through June 2014. Heterogeneity, moderator analysis, publication bias and risk of bias associated with the included studies were examined. A total of 29 RCTs yielding 36 effect sizes were included. The overall effect of acupuncture on cancer‐related pain was ?0.45 [95% confidence interval (CI) = ?0.63 to ?0.26]. The subanalysis indicated that acupuncture relieved malignancy‐related and surgery‐induced pain [effect size (g) = ?0.71, and ?0.40; 95% CI = ?0.94 to ?0.48, and ?0.69 to ?0.10] but not CT‐ or RT‐induced and HT‐induced pain (g = ?0.05, and ?0.64, 95% CI = ?0.33 to 0.24, and ?1.55 to 0.27). Acupuncture is effective in relieving cancer‐related pain, particularly malignancy‐related and surgery‐induced pain. Our findings suggest that acupuncture can be adopted as part of a multimodal approach for reducing cancer‐related pain.     

Calcium intake and colorectal cancer risk: Dose–response meta‐analysis of prospective observational studies

Mechanistic and epidemiologic studies provide considerable evidence for a protective association between calcium intake and incident colorectal cancer (CRC). While the relationship has not been substantiated by short‐duration randomized controlled trials (RCTs) of CRC, trials do show a benefit on adenomas, a precursor to CRC. To address some of this inconsistency, we conducted dose–response meta‐analyses by sources of calcium intake, based on prospective observational studies published up to December 2013 identified from PubMed, Embase, and BIOSIS. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random‐effects model. For total calcium intake, each 300 mg/day increase was associated with an approximately 8% reduced risk of CRC (summary RR = 0.92, 95% CI = 0.89–0.95, I² = 47%, 15 studies with 12,305 cases, intake = 250–1,900 mg/day, follow‐up = 3.3–16 years). While the risk decreased less steeply in higher range of total calcium intake (P_{non‐linearity} = 0.04), the degree of curvature was mild and statistical significance of non‐linearity was sensitive to one study. For supplementary calcium, each 300 mg/day increase was associated with an approximately 9% reduced risk of CRC (summary RR = 0.91, 95% CI = 0.86–0.98, I² = 67%, six studies with 8,839 cases, intake = 0–1,150 mg/day, follow‐up = 5–10 years). The test for non‐linearity was not statistically significant (P_{non‐linearity} = 0.11). In conclusion, both dietary and supplementary calcium intake may continue to decrease CRC risk beyond 1,000 mg/day. Calcium supplements and non‐dairy products fortified with calcium may serve as additional targets in the prevention of CRC. RCTs of calcium supplements with at least 10 years of follow‐up are warranted to confirm a benefit of calcium supplements on CRC risk.     

Tobacco smoking and risk of multiple myeloma: A meta‐analysis of 40 observational studies

This meta‐analysis aims to quantitatively synthesize all available data on the association between tobacco smoking and multiple myeloma (MM) risk. Eligible studies were identified and pooled effect estimates (odds ratios and relative risks) were calculated regarding ever, current and former smoking. Separate analyses were performed on case–control and cohort studies, as well as on males and females. Meta‐regression analysis with percentage of males, mean age, years of smoking, pack‐years, cigarettes per day, years since quit and age at onset was performed. Forty articles were deemed eligible; of them 27 used a case–control design (4,625 cases and 21,591 controls) and 13 used a cohort design (2,228 incident cases among a total cohort size equal to 1,852,763 subjects). Ever smoking was not associated with MM risk (pooled effect estimate = 0.92, 95% confidence interval (CI): 0.85–1.00); similar results were obtained for current (pooled effect estimate = 0.87, 95% CI: 0.74–1.03) and former smoking (pooled effect estimate = 1.04, 95% CI: 0.96–1.13). Regarding ever smoking, the null association was reproducible upon cohort studies (pooled effect estimate = 1.01, 95%CI: 0.89–1.15), whereas the inverse association in case–control studies (pooled effect estimate = 0.87, 95% CI: 0.78–0.96) was particularly due to the bias‐prone hospital‐based ones. Meta‐regression analysis did not yield statistically significant results. In conclusion, MM does not seem to be associated with tobacco smoking. There is a need to further explore how molecular mechanisms are involved in the resistance of MM progenitor cells toward smoking.     

Coffee consumption and risk of colorectal cancer: A systematic review and meta‐analysis of prospective cohort studies

An inverse association between coffee consumption and the risk of colorectal cancer has been found in several case‐control studies, but such an association was not consistent in prospective cohort studies. We conducted a systematic meta‐analysis of prospective cohort studies on coffee consumption and colorectal cancer published up to June 2008. We combined relative risks (RR) for colorectal cancer comparing high vs. low categories of coffee consumption using random‐effects models. We identified 12 eligible cohort studies, which included 646,848 participants and 5,403 cases for colorectal cancer. The summarized result of the meta‐analysis comparing high‐ vs. low‐consumption categories showed no significant effect of coffee consumption on colorectal cancer risk (RR = 0.91; 95% confidence intervals [CI]: 0.81–1.02). The RR was 0.93 (95% CI: 0.71–1.22) when considering 4 studies conducted in the United States of America, 0.91 (95% CI: 0.76–1.10) for 5 studies from Europe, and 0.83 (95% CI: 0.62–1.10) for 3 Japanese studies. No significant differences by sex and cancer‐site were found, but there was a slight suggestion of an inverse association between coffee consumption and colon cancer in women (RR = 0.79; 95% CI: 0.60–1.04), especially Japanese women (RR = 0.62; 95% CI: 0.37–1.05). The suggestive inverse associations were slightly stronger in studies that controlled for smoking and alcohol, and in studies with shorter follow‐up times. Information on coffee type, its serving size, or brewing method may provide a better understanding of this reassuring result and the real role of coffee on colorectal cancer risk. © 2008 Wiley‐Liss, Inc.     

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.     

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.     

Promising biomarkers for predicting the outcomes of patients with KRAS wild‐type metastatic colorectal cancer treated with anti‐epidermal growth factor receptor monoclonal antibodies: A systematic review with meta‐analysis

KRAS mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti‐epidermal growth factor receptor monoclonal antibodies (anti‐EGFR MoAbs). However, many patients with KRAS wild‐type tumors still do not respond to the treatment. We conducted a systematic review with meta‐analysis to assess whether BRAF mutations, PIK3CA mutations and PTEN loss can predict the outcomes of patients with KRAS wild‐type mCRC treated with anti‐EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression‐free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random‐effects model. BRAF mutations, PIK3CA exon 20 mutations and PTEN loss were all associated with shorter PFS (HR = 2.59, 95% CI 1.67–4.03; HR = 2.52, 95% CI 1.33–4.78 and HR = 1.75, 95% CI 1.19–2.56, respectively), shorter OS (HR = 2.74, 95% CI 1.79–4.19; HR = 3.29, 95% CI 1.60–6.75 and HR = 1.85, 95% CI 1.30–2.64, respectively) and lower ORR (RD = ?36%, 95% CI ?44 to ?28%; RD = ?38%, 95% CI ?51 to ?24% and RD = ?41%, 95% CI ?68 to ?14%, respectively). PIK3CA exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of better outcomes in KRAS wild‐type mCRC treated with anti‐EGFR MoAbs. However, the quality of included studies varied, and some of the meta‐analyses were limited by significant between‐study heterogeneity. In the future, well‐designed large randomized controlled trials conducted in KRAS wild‐type mCRC patients with subgroup analysis according to BRAF, PIK3CA exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.     

Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta‐analysis

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme “HMG CoA reductase” and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta‐analysis of 10 studies, statin use was associated with improved recurrence‐free survival (RFS; HR 0.64; 95% CI 0.53–0.79, I² = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59–0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44–1.46). Statin users similarly showed improved overall survival in a meta‐analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44–0.99, I² = 89%). Statin users also had improved cancer‐specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46–1.06, I² = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence‐free survival. Statin users also had improved overall survival and cancer‐specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.