Meta-analyses of colorectal cancer risk factors

Purpose

Demographic, behavioral, and environmental factors have been associated with increased risk of colorectal cancer (CRC). We reviewed the published evidence and explored associations between risk factors and CRC incidence.

Methods

We identified 12 established non-screening CRC risk factors and performed a comprehensive review and meta-analyses to quantify each factor’s impact on CRC risk. We used random-effects models of the logarithms of risks across studies: inverse-variance weighted averages for dichotomous factors and generalized least squares for dose–response for multi-level factors.

Results

Significant risk factors include inflammatory bowel disease (RR = 2.93, 95 % CI 1.79–4.81); CRC history in first-degree relative (RR = 1.80, 95 % CI 1.61–2.02); body mass index (BMI) to overall population (RR = 1.10 per 8 kg/m² increase, 95 % CI 1.08–1.12); physical activity (RR = 0.88, 95 % CI 0.86–0.91 for 2 standard deviations increased physical activity score); cigarette smoking (RR = 1.06, 95 % CI 1.03–1.08 for 5 pack-years); and consumption of red meat (RR = 1.13, 95 % CI 1.09–1.16 for 5 servings/week), fruit (RR = 0.85, 95 % CI 0.75–0.96 for 3 servings/day), and vegetables (RR = 0.86, 95 % CI 0.78–0.94 for 5 servings/day).

Conclusions

We developed a comprehensive risk modeling strategy that incorporates multiple effects to predict an individual’s risk of developing CRC. Inflammatory bowel disease and history of CRC in first-degree relatives are associated with much higher risk of CRC. Increased BMI, red meat intake, cigarette smoking, low physical activity, low vegetable consumption, and low fruit consumption were associated with moderately increased risk of CRC.     

Thyroid cancer risk and smoking status: a meta-analysis

Purpose

Previous researchers have reported an inverse association between cigarette smoking and thyroid cancer risk. To summarize the role of smoking in relation to thyroid cancer occurrence, we conducted a meta-analysis.

Methods

We performed a meta-analysis of 31 eligible studies to summarize the data describing the association between thyroid cancer occurrence and smoking. The case–control studies consisted of 6,260 thyroid cancer cases and 32,935 controls. Cohort studies contained 2,715 thyroid cancer patients that participated from recruitment to follow-up. Q-statistic and I ² statistic were calculated to examine heterogeneity. Summary relative risks (RRs) and 95 % confidence intervals (95 % CIs) were calculated using a random effects model. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, and publication biases were estimated.

Results

Thyroid cancer risk was reduced in persons who had ever-smoked (RR = 0.79; 95 % CI 0.70–0.88) compared with never-smokers. However, strong evidence of heterogeneity was found among the investigated studies; therefore, subgroup analyses were conducted according to study type, smoking status, study location, source of controls, sex, and histological type of thyroid cancer. When the data were stratified by smoking status, an inverse association was observed only among current smokers (RR = 0.74; 95 % CI 0.64–0.86), not former smokers (RR = 1.01; 95 % CI 0.92–1.10). An inverse association was observed only in case–control studies (RR = 0.75; 95 % CI 0.66–0.85).

Conclusions

This meta-analysis of geographically diverse epidemiological data suggests that smoking, particularly current smoking, may influence susceptibility to thyroid cancer. Further well-designed studies with larger sample sizes should be conducted.     

Association of MTHFR C677T polymorphisms and colorectal cancer risk in Asians: evidence of 12,255 subjects

Objectives

To investigate the relationship of the MTHFR polymorphisms (C677T) and the risk of CRC by meta-analysis.

Methods

Relevant literatures concerning the association between the MTHFR C677T polymorphism and the risk of CRC were searched using the electronic database PubMed, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI). Odds ratio (ORs) and 95 % confidence intervals (CIs) were determined to assess the gene–disease association using fixed or random effect models, according to the heterogeneity among included studies.

Results

The study shows that the MTHFR 677 TT homozygous genotype significantly decreases the risk of CRC in Asians (TT vs. CC: OR = 0.82, 95 % CI 0.73–0.92; TT vs. CT: OR = 0.84, 95 % CI 0.75–0.94; TT vs. CC+TT: OR = 0.83, 95 % CI 0.75–0.93).

Conclusion

This meta-analysis indicated that the MTHFR 677 TT homozygous genotype decreased the risk of CRC in Asians, while the MTHFR 677 CT heterozygous genotype did not contribute to CRC susceptibility.     

C-reactive protein,interleukin-6 and the risk of colorectal cancer: a meta-analysis

Purpose

Many studies have evaluated the associations between pre-diagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6) and colorectal cancer risk, but their results are inconsistent. We therefore conducted a meta-analysis to investigate these associations.

Methods

A comprehensive literature search up to October 2013 was undertaken in PubMed. Pooled relative risk (RR) estimates and 95 % confidence intervals (CIs) were used to calculate estimated effect.

Results

Eighteen studies on CRP comprising a total of 4,706 colorectal cancer cases were included in this meta-analysis. The summary RR of colorectal cancer for one unit change in natural logarithm (ln) CRP was 1.12 [95 % CI (1.05–1.21)]. There was statistically significant heterogeneity among studies (p = 0.006; I ² = 51.7 %). After excluding the studies contributing most to the heterogeneity, summary estimate was essentially unchanged. In addition, the association was significant for colon cancer [RR = 1.13, 95 % CI (1.05–1.21)], not for rectal cancer [RR = 1.03, 95 % CI (0.90–1.17)]. We also found that CRP was significantly associated with increased risk of colorectal cancer among men, but not among women. There were six studies on IL-6 that involved a total of 1,068 colorectal cancer cases. The pooled RR of colorectal cancer for one unit change in ln IL-6 was 1.10 (95 % CI 0.88–1.36), and no statistically significant heterogeneity was found (p = 0.175; I ² = 34.8 %).

Conclusion

Our results suggest that pre-diagnostic circulating CRP is associated with increased risk of colorectal cancer. However, there is no significant association between IL-6 and colorectal cancer risk.     

Association between non-steroidal anti-inflammatory drug use and melanoma risk: a meta-analysis of 13 studies

Purpose

Results of the association between non-steroidal anti-inflammatory drugs (NSAIDs) and melanoma risk have been inconsistent. We performed a meta-analysis of relevant studies to investigate the hypothesis of an association between NSAID use and melanoma risk.

Methods

Systematic searches of the PubMed and several other databases up to 23 March 2013 were retrieved. All epidemiologic studies regarding NSAIDs and melanoma risk were included. Fixed- or random-effects meta-analytical models were used to calculate relative risk (RR) and corresponding 95 % confidence intervals (CIs). Sensitivity analyses, Galbraith plots, and subgroup analyses were also performed.

Results

Six case–control studies including 93,432 melanoma cases and 401,251 controls, six cohort studies consisting of 563,380 subjects, and one randomized controlled trial encompassing 39,876 participants were included in this analysis. Compared to non-use, ever use of any NSAIDs was not statistically significantly associated with melanoma risk based on the random-effects models (RR = 0.97, 95 % CI = 0.90–10.4, p = 0.401). No differences were found in the effects on melanoma risk of aspirin, non-aspirin NSAIDs, and cyclooxygenase-2 inhibitor use overall and stratified by gender. However, a slight reduction in the risk of melanoma by taking aspirin was observed in case–control studies (RR = 0.88, 95 % CI = 0.80–0.96, p = 0.004).

Conclusions

Findings from this pooled analysis do not support the hypothesis that NSAID use provides potential benefits in preventing melanoma. More and larger randomized trials, including adequate numbers of patients, are required to further evaluate the relationship between NSAID use and melanoma.     

Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer

Objective

Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies.

Methods

Study- and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards models and then pooled using a random-effects model.

Results

Among 725,134 participants, 5,720 incident colon cancers were diagnosed during follow-up. The pooled multivariate RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of intake were 0.92 (95% CI 0.84–1.00, p-value, test for between-studies heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77–0.95, p-value, test for between-studies heterogeneity = 0.42) for total folate. Results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78–0.98, comparing ≥560 mcg/days vs. <240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous variable, a 2% risk reduction (95% CI 0–3%) was estimated for every 100 μg/day increase in total folate intake.

Conclusion

These data support the hypothesis that higher folate intake is modestly associated with reduced risk of colon cancer.     

Eating frequency and risk of colorectal cancer

Purpose

Eating frequency is a modifiable aspect of dietary behavior that may affect risk of colorectal cancer (CRC). Although most previous case–control studies indicate a positive association, two prospective studies suggest an inverse association between eating frequency and CRC risk, with evidence of effect modification by diet composition. We examined the association between eating frequency and CRC in a large, prospective cohort study, and explored whether this relationship was modified by sex, coffee consumption, or dietary glycemic load.

Methods

Between 2000 and 2002, 67,912 western Washington residents aged 50–76 reported average daily meal and snack frequency using a mailed questionnaire as part of the vitamins and lifestyle study. Participants were followed for CRC through linkage with SEER through 2008, over which time 409 CRC cases developed. Hazard Ratios and 95 % Confidence Intervals were obtained using Cox regression.

Results

In age- and sex-adjusted models higher (5+ times/d) vs. lower (1–2 times/d) eating frequency was associated with a HR of 0.62 (95 % CI 0.43?0.88, P_trend = 0.001). However, following further adjustment for BMI, race/ethnicity, alcohol, and other known CRC risk factors, the relationship was no longer statistically significant (HR: 0.76; 95 % CI 0.51, 1.14). No effect modification was observed by sex (P_interaction = 0.45), coffee consumption (P_interaction = 0.44), or dietary glycemic load (P_interaction = 0.90). In subgroup analyses by tumor site, higher vs. lower eating frequency was associated with lower risk for colon (HR 0.65 95 % CI 0.39–1.07, P_trend = 0.04), but not rectal cancers (HR = 1.08 95 % CI 0.54–2.18, P_trend = 0.94).

Conclusion

The weak inverse association observed between eating frequency and CRC is consistent with findings from other prospective studies. Modification of this relationship by diet quality and participant characteristics should be considered in the future studies.     

Total calcium intake and colorectal adenoma in young women

Background

Total calcium intake appears to reduce occurrence of colorectal adenoma; however, the dose necessary for prevention in young women is unclear. We examined fine categories of calcium intake in relation to occurrence of first colorectal adenoma in a cohort of mostly premenopausal (88 %) women aged 26–60 at time of endoscopy.

Design

We conducted an analysis among 41,403 participants in the Nurses’ Health Study II and assessed intakes of calcium prior to endoscopy through participants’ responses to biannual questionnaires.

Results

Between 1991 and 2007, we documented 2,273 colorectal adenoma cases. There was a significant trend across categories of calcium intakes with lowest intakes suggestive of higher occurrence of adenoma (p = 0.03) and those in the distal colon (p = 0.03) and rectum (p = 0.04). Compared with 1,001–1,250 mg/day of calcium intake, ≤500 mg/day was suggestive of a modest increase in occurrence of adenoma (multivariable RR = 1.21, 95 % CI 0.90–1.61); there were also suggestions of an increased risk with >500 to ≤700 mg/day of calcium. The association between ≤500 mg/day of calcium intake and adenoma was stronger for multiple (RR = 2.27, 95 % CI 1.38, 3.72), large (≥1 cm) (RR = 2.01, 95 % CI 1.27, 3.21), and high-risk adenoma (≥1 cm or mention of villous histology/high-grade dysplasia) (RR = 1.76, 95 % CI 1.13, 2.72). No differences in associations were noted between jointly categorized calcium and phosphorus or magnesium intakes.

Conclusions

Our findings suggest that low intakes of calcium, <500 and possibly 500–700 mg/day, in younger women are associated with an increased risk of multiple and advanced colorectal adenoma.     

Circulating leptin levels and risk of colorectal cancer and adenoma: a case–control study and meta-analysis

Purpose

Equivocal results regarding the role of leptin in colorectal cancer (CRC) and adenoma (CRA) have been reported. A case–control study investigating the association of leptin with CRC risk and clinicopathological characteristics along with meta-analysis of published data on both CRC and CRA were conducted.

Methods

Pubmed and Embase were searched for the meta-analysis, comprising 28 case–control studies amounting 3,614 CRC and 1,215 CRA cases, along with 5,220 controls. Meticulous contact with the authors of individual studies was undertaken for the provision of additional data. Pooling of standardized mean differences (SMD), relative risks (RR) and 95 % CI (random effects models), subgroup, sensitivity, and meta-regression analyses were conducted.

Results

The meta-analysis suggested positive association of serum leptin with CRA (RR, 95 % CI 1.35, 1.03 to +1.76), but not CRC either at the pooled analysis on SMDs or RRs (SMD, 95 % CI 0.18, ?0.04 to +0.40; RR, 95 % CI 1.04, 0.65 to +1.65). Significant heterogeneity between studies on CRC as well as between studies on CRA providing SMD was noted. Subgroup, meta-regression and sensitivity analyses highlighted potential methodology-, design-, size- and quality-related effect modifiers.

Conclusions

Meta-analysis of current evidence suggests positive association of serum leptin with CRA but not with CRC risk. Given the case–control nature of available studies, the limited number of studies on serum leptin and CRA, and the heterogeneity of CRC studies, carefully designed, prospective studies preferably reporting RRs adjusted for a variety of confounders may be warranted.     

Postdiagnosis body mass index and risk of mortality in colorectal cancer survivors: a prospective study and meta-analysis

Purpose

Aim of this study was to investigate the association between postdiagnosis body mass index (BMI) and all-cause mortality in colorectal cancer (CRC) survivors in a prospective study and meta-analysis.

Methods

We conducted a prospective cohort study on 2,143 CRC survivors in Germany. Participants were recruited to the study on average 4 years after diagnosis, and postdiagnosis BMI was assessed at recruitment using a self-administered questionnaire. CRC survivors were followed up for a mean time of 3.5 years. The association between BMI and all-cause mortality was investigated using multivariable Cox proportional hazards models. Additionally, we performed a meta-analysis of studies on postdiagnosis BMI and all-cause mortality (n = 5, including this study) by applying random-effects models.

Results

In the prospective analysis, 349 participants died. BMI was not statistically significantly associated with all-cause mortality. Compared to normal weight survivors, the hazard ratios (HRs) [95 % confidence interval (CI)] for all-cause mortality in underweight, overweight and obese survivors were 1.65 (0.79–3.45), 0.80 (0.62–1.03) and 0.84 (0.62–1.14), respectively. In the meta-analysis, individuals with underweight were at increased risk for all-cause mortality [HR (95 % CI) 1.72 (1.18–2.49)], whereas individuals with overweight had a lower risk [HR (95 % CI) 0.79 (0.71–0.88)], compared to normal weight subjects. For obesity, the risk of mortality was also reduced with only borderline significance [HR (95 % CI) 0.88 (0.77–1.00)].

Conclusions

While the present study as well as single previously published studies showed that overweight was associated with a non-significant reduced risk for all-cause mortality, our meta-analysis indicated a decreased mortality risk among overweight CRC survivors.     

Trastuzumab combined with doublet or single-agent chemotherapy as first-line therapy for HER2-positive metastatic breast cancer

Purpose

To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC).

Methods

We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766.

Results

The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63–0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88–0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98–1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H.

Conclusions

Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

     

Colonoscopy reduced distal colorectal cancer risk and excess cancer risk associated with family history

Purpose

Colonoscopy efficacy at preventing proximal colorectal cancer (CRC) is questioned, and little is known about efficacy in high-risk versus medium-risk populations. We investigated the relationship between colonoscopy screening, family history of colorectal cancer (FHCC), and CRC risk by site.

Methods

Among 92,078 women of the E3N prospective cohort, 692 CRCs have been diagnosed after a median follow-up of 15.4 years. Cox proportional hazard models estimated adjusted hazards ratios according to subsites of cancer and FHCC.

Results

A personal history of colonoscopy (PHC; n = 37,470) was associated with decreased rectal and distal colon cancer risks (hazard ratio (HR) = 0.57; 95 % Confidence Interval (CI) = 0.42–0.78 and HR = 0.37; 95 % CI = 0.26–0.52, respectively), but not proximal colon cancer risk (HR = 0.87; 95 % CI = 0.64–1.18). In women with no prior colonoscopy, those with FHCC had a 80 % higher CRC risk than those without FHCC. In women with previous colonoscopy, CRC risk was similar in women with and without FHCC (p for interaction = 0.04).

Conclusions

Results showed colonoscopy ability to prevent distal cancers, but not proximal cancers in women. Colonoscopy screening also reduced the excess risk of women with FHCC to that of women with no FHCC.     

Racial disparities in advanced-stage colorectal cancer survival

Purpose

African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival.

Methods

The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan–Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI.

Results

We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06–1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01–1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82–1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years.

Conclusions

Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.     

Legume intake and the risk of cancer: a multisite case–control study in Uruguay

Background

Previous studies have suggested that a high intake of legumes may decrease the risk of stomach and prostate cancer and some other cancers. However, the evidence is still limited. To further explore the association between legume intake and cancer risk we conducted a case–control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls.

Results

The highest versus the lowest tertile of legume intake was associated with a significant decrease in the risk of cancers of the oral cavity and pharynx (OR = 0.48, 95% CI: 0.34–0.68), esophagus (OR = 0.54, 95% CI: 0.38–0.77), larynx (OR = 0.55, 95% CI: 0.40–0.77), upper aerodigestive tract (OR = 0.50, 95% CI: 0.40–0.63), stomach (OR = 0.69, 95% CI: 0.49–0.97), colorectum (OR = 0.43, 95% CI: 0.32–0.59), kidney (OR = 0.41, 95% CI: 0.24–0.71), and all sites combined (OR = 0.68, 95% CI: 0.59–0.78). No significant association was observed between legume intake and cancers of the lung (OR = 1.03, 95% CI: 0.83–1.27), breast (OR = 0.89, 95% CI: 0.65–1.20), prostate (OR = 0.87, 95% CI: 0.64–1.18) or bladder (OR = 0.82, 95% CI: 0.57–1.17). Similar results were found for both beans and lentils.

Conclusion

Higher intake of legumes was associated with a decreased risk of several cancers including those of the upper aerodigestive tract, stomach, colorectum, and kidney, but not lung, breast, prostate or bladder. Further investigations of these associations in prospective cohort studies are warranted.     

Territorial inequalities in management and conformity to clinical guidelines for sarcoma patients: an exhaustive population-based cohort analysis in the Rhône-Alpes region

Background

Sarcomas are rare cancers with great variability in clinical and histopathological presentation. The main objective of clinical practice guidelines (CPGs) is to standardize diagnosis and treatment.

Methods

From March 2005 to February 2007, all patients diagnosed with localized sarcoma in the Rhône-Alpes region were included in a cohort-based study, to evaluate the compliance of sarcoma management with French guidelines in routine practice and to identify predictive factors for compliance with CGPs.

Results

634 (71 %) patients with localized sarcoma satisfying the inclusion criteria were included out of 891 newly diagnosed sarcomas. Taking into account initial diagnosis until follow-up, overall conformity to CPGs was only 40 % [95 % confidence interval (CI) = 36–44], ranging from 54 % for gastrointestinal stromal tumor to 36 % for soft tissue sarcoma and 42 % for bone sarcoma. In multivariate analysis, primary tumor type [relative risk (RR) = 4.42, 95 % CI = 2.79–6.99, p < 0.001], dedicated multidisciplinary staff before surgery (RR = 4.19, 95 % CI = 2.39–7.35, p < 0.001) and management in specialized hospitals (RR = 3.71, 95 % CI = 2.43–5.66, p < 0.001) were identified as unique independent risk factors for conformity to CPGs for overall treatment sequence.

Conclusions

With only 40 % of total conformity to CPGs, the conclusions support the improvement of initial sarcoma management and its performance in specialized centres or within specialized dedicated networks.     

Consumption of dairy and meat in relation to breast cancer risk in the Black Women’s Health Study

Purpose

Dairy and meat consumption may impact breast cancer risk through modification of hormones (e.g., estrogen), through specific nutrients (e.g., vitamin D), or through products formed in processing/cooking (e.g., heterocyclic amines). Results relating meat and dairy intake to breast cancer risk have been conflicting. Thus, we examined the risk of breast cancer in relation to intake of dairy and meat in a large prospective cohort study.

Methods

In the Black Women’s Health Study, 1,268 incident breast cancer cases were identified among 52,062 women during 12 years of follow-up. Multivariable (MV) relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models.

Results

Null associations were observed for total milk (MV RR = 1.05, 95 % CI 0.74–1.46 comparing ≥1,000–0 g/week) and total meat (MV RR = 1.04, 95 % CI 0.85–1.28 comparing ≥1,000 < 400 g/week) intake and risk of breast cancer. Associations with intakes of specific types of dairy, specific types of meat, and dietary calcium and vitamin D were also null. The associations were not modified by reproductive (e.g., parity) or lifestyle factors (e.g., smoking). Associations with estrogen receptor (ER) positive (+), ER negative (?), progesterone receptor (PR) +, PR?, ER+/PR+, and ER?/PR? breast cancer were generally null.

Conclusions

This analysis of African-American women provides little support for associations of dairy and meat intake with breast cancer risk.     

Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies

Background

Epidemiologic findings concerning the associations between intakes of heme iron and zinc and colorectal cancer (CRC) incidence yielded conflicting results. We aimed to investigate the associations by performing a meta-analysis of prospective studies.

Methods

We conducted a literature search on PubMed and EMBASE databases up to December 2012 to identify the prospective studies that investigated the relationships between heme iron or zinc intake and risk of CRC. We also reviewed the bibliographies of the retrieved articles to identify additional studies. We used a random-effects model to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs).

Results

Eight studies on heme iron intake and six studies on zinc intake met the inclusion criteria. The summary RR of CRC for the highest versus the lowest intake was 1.14 (95 % CI = 1.04–1.24) for heme iron and 0.83 (95 % CI = 0.72–0.94) for zinc, respectively. The observed associations were not significantly modified by subsites within the colorectum, sex, geographic area, study duration, the number of cases, or the range of intakes. In the dose–response analyses, the summary RR of CRC was 1.11 (95 % CI = 1.03–1.18) for heme iron intake of 1 mg/day, and 0.86 (95 % CI = 0.78–0.96) for zinc intake of 5 mg/day, respectively. There was little evidence of publication bias.

Conclusion

This meta-analysis suggests a significant positive dose–response association of heme iron intake and a significant inverse dose–response association of zinc intake with risk of CRC.     

Statins and colorectal cancer risk: a longitudinal study

Purpose

Studies evaluating the association between statins and colorectal cancer (CRC) have used various methods to address bias and have reported mixed findings. We sought to assess the association in a large cohort of residents in Emilia-Romagna, Italy, using multiple methods to address different sources of confounding. We also sought to explore potential effect measure modification by sex.

Methods

We conducted a retrospective cohort study using the 2003–2010 healthcare database of Emilia-Romagna, Italy. We identified all initiators of statins; initiators of glaucoma medications served as the comparison group to account for confounding by healthy user bias. We followed patients longitudinally to identify CRC cases in hospital discharge data. We used multivariable Cox regression analyses to adjust for confounding by CRC risk factors and we conducted a sensitivity analysis using propensity score matching.

Results

After multivariable adjustment, initiators of statins had a lower incidence rate of CRC as compared to initiators of glaucoma drugs [hazard ratio (HR) 0.79; 95 % CI 0.69–0.90]. In sex-stratified analyses we observed a protective effect in men (HR 0.77; 95 % CI 0.67–0.88) but not in women (HR 0.96; 95 % CI 0.82–1.1). Results were similar in propensity score analyses.

Conclusions

After adjusting for observed risk factors, statin initiation versus glaucoma drug initiation was associated with a reduced risk of CRC in men but not in women. While this study is subject to many limitations, it corroborates a previous study that found sex differences in the association between statins and CRC.     

Paclitaxel plus platinum or gemcitabine plus platinum in first-line treatment of advanced non-small-cell lung cancer: results from 6 randomized controlled trials

Aim

The aim was to compare the efficacy and toxicity of paclitaxel plus platinum (TP) with gemcitabine plus platinum (GP) in untreated advanced non-small-cell lung cancer by a meta-analysis.

Methods

An extensive literature search was performed for relevant randomized controlled trials. Studies were evaluated for eligibility and quality, and then the data were extracted and analyzed using Review Manager 5.1 software. Publication bias was evaluated according to Begg’s funnel plot and Egger’s test using Stata/SE version 10.1 software.

Results

Six randomized controlled trials including 2,793 patients were ultimately identified. The meta-analysis demonstrated that the efficacy was comparable between TP and GP regimens according to the pooled relative risks (RRs) for overall response rate [0.99, 95 % confidence interval (CI) = 0.88–1.13, p = 0.92], disease control rate (0.96, 95 % CI = 0.90–1.03, p = 0.24) and 1-year survival (0.99, 95 % CI = 0.90–1.09, p = 0.87), and the hazard ratios for overall survival (1.06; 95 % CI = 1.00–1.13, p = 0.07) and time-to-progression of disease (1.05, 95 % CI = 0.97–1.14, p = 0.20). Grade 3–4 nausea or vomiting, anemia and thrombocytopenia were less frequent in the TP group (RR = 0.53, 95 % CI = 0.35–0.78, p = 0.002; RR = 0.37, 95 % CI = 0.30–0.45, p < 0.00001; RR = 0.20, 95 % CI = 0.14–0.27, p < 0.00001; respectively). Grade 3–4 sensory neuropathy, fatigue and neutropenia were comparable between the two groups. Sensitivity analyses in studies of paclitaxel compared with gemcitabine combined with the same platinum strengthened the above conclusion.

Conclusions

Our meta-analysis showed that paclitaxel plus platinum had similar efficacy and less toxicity compared with gemcitabine plus platinum in first-line treatment of advanced non-small-cell lung cancer.     

Meta-analysis for psychological impact of breast reconstruction in patients with breast cancer

Aims

This meta-analysis aimed to evaluate the impact of breast reconstruction on the psychological aspects in patients with breast cancer.

Methods

A literature search on PubMed, Embase, ScienceDirect and Google scholar databases was conducted up to September 2017. The pooled risk radio (RR) or standard mean difference (SMD) and the corresponding 95% confidence intervals (CIs) were calculated using the RevMan 5.3 software.

Results

A total of 5 studies were included in this meta-analysis. There were 551 breast cancer patients receiving mastectomy plus breast reconstruction and 574 breast cancer patients receiving mastectomy alone. The results showed that breast reconstruction can significantly decrease the incidence of anxiety (RR = 0.62, 95% CI 0.47–0.82, P = 0.0006)/depression (RR = 0.54, 95% CI 0.32–0.93, P = 0.02) and scale score for evaluating anxiety (SMD = ? 0.20, 95% CI ? 0.37 to ? 0.03, P = 0.02)/depression (SMD = ? 0.22, 95% CI ? 0.39 to ? 0.66, P = 0.007) compared with mastectomy alone.

Conclusions

Breast reconstruction after mastectomy was benefit for improving the psychological damages in patients with breast cancer.