Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis

Background:

Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.

Methods:

We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose–response meta-regression models and investigated potential sources of heterogeneity.

Results:

A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose–risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin''s and Non-Hodgkin''s lymphomas were inversely associated.

Conclusions:

Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.     

Coffee consumption and risk of colorectal cancer: a meta-analysis of case–control studies

A meta-analysis of case–control studies on coffee consumption and colorectal cancer risk was conducted. Twenty-four eligible studies published before May 2010 were identified, including a total of 14,846 cases of colorectal, colon or rectal cancer. Compared to non/occasional drinkers, the odds ratios (OR) for drinkers were 0.83 (95% CI 0.73–0.95) for colorectal, 0.93 (95% CI 0.81–1.07) for colon and 0.98 (95% CI 0.85–1.13) for rectal cancer, with significant heterogeneity among studies; the corresponding ORs for the increment of 1 cup/day were 0.94 (95% CI 0.91–0.98), 0.95 (95% CI 0.92–0.98), and 0.97 (95% CI 0.95–0.99). For the highest coffee drinkers, the ORs were 0.70 (95% CI 0.60–0.81) for colorectal cancer, 0.75 (95% CI 0.64–0.88) for colon cancer and 0.87 (95% CI 0.75–1.00) for rectal cancer, when compared to non/low drinkers. The results of this meta-analysis of case–control studies suggest a moderate favorable effect of coffee consumption on colorectal cancer risk. The reduced risk was consistent across study design (hospital vs. population based), geographic area, and various confounding factors considered. It may reflect a real protection but also partly or largely be due to reverse causation, i.e. decreased coffee consumption among cases following the onset of bowel symptoms.     

Antioxidant vitamins and the risk of endometrial cancer: a dose–response meta-analysis

Antioxidant vitamins may reduce cancer risk by limiting oxidative DNA damage. To summarize and quantify the current epidemiologic evidence of an association between antioxidant vitamin intake and endometrial cancer, we conducted a systematic literature review and meta-analysis. One cohort and 12 case–control studies presenting relevant risk estimates were identified by conducting bibliographical searches through June 2008. Dose–response meta-analyses were conducted for beta-carotene, vitamin C, and vitamin E from food sources. Intake from supplements was not considered in the meta-analyses because of the few studies that reported relevant information. Based on case–control data, the random-effects summary odds ratios (OR) were, for beta-carotene: 0.88 (95% CI: 0.79–0.98) per 1,000 mcg/1,000 kcal (I²: 77.7%; p < 0.01); for vitamin C: 0.85 (95% CI: 0.73–0.98) per 50 mg/1,000 kcal (I²: 66.1%; p < 0.01); and, for vitamin E: 0.91 (95% CI: 0.84–0.99) per 5 mg/1,000 kcal (I²: 0.0%; p: 0.45). In contrast, the only prospective study identified provided little indication of an association. Although the current case–control data suggest an inverse relationship of endometrial cancer risk with dietary intakes of beta-carotene, vitamin C, and vitamin E from food sources, additional studies are needed, particularly cohort studies, to confirm an association.     

Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose–response meta-analysis

Objective  

We systematically reviewed and meta-analyzed literature examining associations of vitamin D (dietary intake, circulating 25-hydroxy-vitamin-D (25(OH)D), and 1,25-dihydroxy-vitamin-D (1,25(OH)₂D) concentrations) with prostate cancer.     

Intake of fruit and vegetables and risk of bladder cancer: a dose–response meta-analysis of observational studies

Background

Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial.

Methods

We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose–response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013.

Results

Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69–0.99) for total fruit and vegetables, 0.81 (0.70–0.93) for total vegetables, 0.77 (0.69–0.87) for total fruit, 0.84 (0.77–0.91) for cruciferous vegetables, 0.79 (0.68–0.91) for citrus fruits, and 0.74 (0.66–0.84) for yellow–orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P _{for nonlinearity} = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78–0.96), 0.80 (0.67–0.94), 0.79 (0.66–0.94), 0.79 (0.65–0.96), and 0.79 (0.64–0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow–orange vegetable intake with risk of bladder cancer risk (P _{for nonlinearity} = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow–orange vegetables.

Conclusion

This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.     

Anthropometric factors and endometrial cancer risk: a systematic review and dose–response meta-analysis of prospective studies

BackgroundGreater body mass index (BMI) has been convincingly related to increased endometrial cancer risk, however, whether adiposity earlier in life or abdominal fatness is an independent risk factor and whether weight gain or greater height increases the risk is not clear.MethodsAs part of the Continuous Update Project of the World Cancer Research Fund International, we conducted a systematic review and meta-analysis of prospective studies of the association between anthropometric measures and endometrial cancer risk and searched PubMed and several other databases up to February 2015. Summary relative risks (RRs) were calculated using a random-effects model.ResultsThirty prospective studies of BMI and endometrial cancer risk with 22 320 cases among 6 445 402 participants were included. The summary RR for a 5-unit increment was 1.54 [95% confidence interval (CI) 1.47–1.61, I² = 81%]. Although the test for non-linearity was significant, P_{non-linearity} < 0.0001, and the curve was steeper within the overweight and obese BMI ranges, there was evidence of increased risk even within the high normal BMI range. The summary RR was 1.45 (95% CI 1.28–1.64, I² = 76%) per 5 BMI units for BMI in young adulthood, 1.18 (95% CI 1.14–1.23, I² = 67%) per 5 kg increase of weight, and 1.16 (95% CI 1.12–1.20, I² = 51%) per 5 kg of weight gained between young adulthood and study baseline, 1.27 (95% CI 1.17–1.39, I² = 71%) per 10 cm increase in waist circumference, 1.21 (95% CI 1.13–1.29, I² = 0%) per 0.1-unit increment in waist-to-hip ratio and 1.30 (95% CI 1.19–1.41, I² = 0%) per 10-cm increase in hips circumference. The summary RR was 1.15 (95% CI 1.09–1.22, I² = 61%) for a 10-cm increase in height.ConclusionsAll measures of adiposity were associated with increased risk of endometrial cancer, and in addition increasing height was associated with increased risk.     

Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies

BackgroundThe International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2–3 drinks/day) alcohol drinking, investigation of the dose–response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region.MethodsTwenty-seven cohort and 34 case–control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose–risk relation.ResultsThe RRs were 1.21 [95% confidence interval (CI) 1.13–1.28] for moderate and 1.52 (95% CI 1.27–1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13–1.37) than for women (RR = 1.08, 95% CI 1.03–1.13; P_{heterogeneity} = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33–2.46; P_{heterogeneity} = 0.04). The dose–risk analysis estimated RRs of 1.07 (95% CI 1.04–1.10), 1.38 (95% CI 1.28–1.50), and 1.82 (95% CI 1.41–2.35) for 10, 50, and 100 g/day of alcohol, respectively.ConclusionsThis meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.     

Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose–response meta-analysis

Background:

Epidemiological studies evaluating the association of vitamin B₆, vitamin B₁₂ and methionine with breast cancer risk have produced inconsistent results.

Methods:

Pertinent studies were identified by a search in PubMed and Web of Knowledge. Random-effect model was used. Dose–response relationship was assessed by restricted cubic spline.

Results:

The combined relative risk (95% confidence interval) of breast cancer for the highest vs lowest category of serum pyridoxal 5′-phosphate (PLP, active form of vitamin B₆) levels and dietary methionine intake was 0.80 (0.66–0.98, P=0.03) and 0.94 (0.89–0.99, P=0.03), respectively, and the associations of breast cancer with higher serum PLP levels and dietary methionine intake were significant among post-menopausal women, but not among pre-menopausal women. The inverse association between breast cancer risk and dietary vitamin B₆ intake, serum vitamin B₁₂ levels and dietary vitamin B₁₂ intake was not significant overall. Linear dose–response relationship was found, and the risk of breast cancer decreased by 23% (P<0.00) for every 100 pmol ml⁻¹ increment in PLP levels and 4% (P=0.05) for every 1 g per day increment in dietary methionine intake, respectively.

Conclusion:

Serum PLP levels and methionine intake might be inversely associated with breast cancer risk, especially among postmenopausal women, which need to be confirmed.     

A meta-analysis on dose–response relationship between night shift work and the risk of breast cancer

This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose–response meta-analysis approach.We systematicly searched all cohort and case–control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose–response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies.Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between ‘ever exposed to night shift work’ and breast cancer was 1.19 [95% confidence interval (CI) 1.05–1.35]. Further meta-analyses on dose–response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01–1.05; P_{heterogeneity} < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07–1.21; P_{heterogeneity} = 0.06) increase in breast cancer risk.This systematic review updated the evidence that a positive dose–response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.     

Early-onset baldness and the risk of aggressive prostate cancer: findings from a case–control study

Purpose

We aimed to evaluate the associations between androgenetic alopecia at a young age and subsequent development of aggressive prostate cancer (PC).

Methods

Using a case–control design with self-administered questionnaire, we evaluated the association between aggressive PC and very early-onset balding at age 20, and early-onset balding at age 40 years in 1,941 men. Cases were men with high-grade and/or advanced stage cancer and controls were clinic based men who had undergone biopsy and were found to be histologically cancer negative. Additionally, for cases we assessed whether early-onset balding was associated with earlier onset of disease.

Results

Men with very early-onset balding at age 20 years were at increased risk for subsequent aggressive PC [odds ratio (OR) 1.51, 95% confidence interval (CI) 1.07–2.12] after adjustment for age at baseline, family history of PC, smoking status, alcohol intake, body shape, timing of growth spurt and ejaculatory frequency. Additionally, these men were diagnosed with PC approximately 16 months earlier than cases without the exposure. The effect was present particularly for men with advanced stage pT3+ disease (OR 1.68, 95% CI 1.14–2.47) while men with organ-confined high-grade (8–10) PC did not exhibit the same relationship. No significant associations were observed for men who were balding at age 40 years, given no balding at age 20.

Conclusion

Men with androgenetic alopecia at age 20 years are at increased risk of advanced stage PC. This small subset of men are potentially candidates for earlier screening and urological follow-up.

     

Non-linear dose–response relationship between cigarette smoking and pancreatic cancer risk: Evidence from a meta-analysis of 42 observational studies

BackgroundQuestion remains about the shape of the dose–response relationship between cigarette smoking and pancreatic cancer risk.MethodsRelevant studies were identified by searching PubMed, ISI Web of Science and China National Knowledge Infrastructure (CNKI) databases and by reviewing the reference lists of retrieved articles. Random-effects models were applied to estimate summary relative risks (RRs).ResultsForty-two publications were finally included. The overall meta-analysis showed evidence of non-linear association between smoking intensity and pancreatic cancer risk (P for non-linearity = 0.000). Compared with non-smokers, the summary RRs were 1.5 (95% confidence interval (CI): 1.4, 1.6) for 10 cigarettes/day, 1.9 (95% CI: 1.8, 2.0) for 20 cigarettes/day, 2.0 (95% CI: 1.9, 2.1) for 30 cigarettes/day and 2.1 (95% CI: 1.9, 2.3) for 40 cigarettes/day with marginal between-study heterogeneity (I² = 29%). Similar results were also found for smoking duration and cumulative amount of cigarettes smoked. Besides, the summary RR for former smokers reduced with increasing time since quitting smoking compared with current smokers without heterogeneity (P for non-linearity = 0.008, I² = 0%). The results of stratified analysis by study design were comparable to those of overall meta-analysis. When stratified by sex, non-linear dose–response associations were detected for all metrics of cigarette smoking in women, while linear relationships were observed for smoking duration and cumulative amount of cigarettes smoked in men except for smoking intensity.ConclusionThis meta-analysis reveals a non-linear dose–response association between cigarette smoking and pancreatic cancer risk, but it might differ between sexes.     

Dose–response meta-analysis of silica and lung cancer

Objective  To examine the association between occupational exposure to silica and lung cancer from a systematic review (and meta-analysis) of the epidemiologic literature, with special reference to the methodological quality of observational studies. Methods  We searched Medline, Toxline, BIOSIS, and Embase (1966–December 2007) for original articles published in any language. Observational studies (cohort and case–control studies) were selected if they reported the result of dose–response analyses relating lung cancer to occupational exposure to silica after appropriate adjustment for smoking. Results  Ten studies (4 cohort studies and 6 case–control studies) met the inclusion criteria of the meta-analysis, nine of which contributing to the main analysis (dose–response analysis, no lag time). We found increasing risk of lung cancer with increasing cumulative exposure to silica, with heterogeneity across studies however. Posthoc analyses identified a set of seven more homogeneous studies. Their meta-analysis resulted in a dose–response curve that was not different from that obtained in the main analysis. Conclusion  Silica is a lung carcinogen. This increased risk is particularly apparent when the cumulative exposure to silica is well beyond that resulting from exposure to the recommended limit concentration for a prolonged period of time.     

Dietary calcium intake, vitamin D levels, and breast cancer risk: a dose–response analysis of observational studies

Results from the recent meta-analysis suggested a favorable effect of dietary calcium and vitamin D levels on breast cancer risk. However, the relationship of dietary calcium and vitamin D levels with breast cancer risk is unclear. Thus, the dose–response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that women might suffer from the lowest risk of breast cancer with dietary calcium intake of about 600 mg/day, dietary vitamin D intake of about 400 IU/day, and serum vitamin D levels of about 30 ng/ml.     

Case-control study of alcohol consumption and prostate cancer risk in Montréal, Canada

Objectives: to estimate the risk of prostate cancer associated with alcohol consumption. Methods: Between 1979 and 1985 a population-based case–control study was carried out in Montréal, which accrued over 4000 men in total, including cases of prostate cancer, other cancers, and population controls. The present analysis was restricted to the subset, aged 45–70 years, who underwent face-to-face interviews, in which aspects of lifelong alcohol consumption were ascertained. The cancer control series was further restricted to men whose tumor types were considered unrelated to alcohol consumption. There were 399 incident cases of prostate cancer, 476 population controls, and 674 cancer controls. Results: When using the population controls, risk increased with increasing cumulative consumption of alcohol. There was no decrease in risk after quitting. Risk was particularly high among those who reported having started before age 15 years (odds ratio = 3.8; 95% confidence interval: 1.6–9.3). The results obtained using the cancer controls were less pronounced, but still indicated an excess risk associated with alcohol consumption. Beer was the most prevalent type of alcohol consumed in this population and showed the strongest association with prostate cancer. Conclusions: The results are consistent with an increase in the risk of prostate cancer due to alcohol consumption.     

Alcohol and endometrial cancer risk: a case–control study and a meta-analysis

To evaluate the association between alcohol consumption and endometrial cancer risk, we analyzed data from a hospital-based case–control study, conducted in Italy between 1992 and 2006, on 454 endometrial cancer cases and 908 controls, and performed a meta-analysis updated to October 2009. Compared to never alcohol drinkers, the odds ratio was 1.03 (95% confidence interval, CI, 0.76–1.41) for ≤7, 1.27 (95% CI 0.86–1.87) for 8–14, and 1.19 (95% CI 0.80–1.77) for ≥15 drinks/week, with no trend in risk. No association emerged for wine, beer, and spirit consumption analyzed separately. The meta-analysis included 20 case–control and seven cohort studies, for a total of 13,120 cases. Compared to non/low drinkers, the pooled relative risks for drinkers were 0.90 (95% CI 0.80–1.01) for case–control studies, 1.01 (95% CI 0.90–1.14) for cohort studies, and 0.95 (95% CI 0.88–1.03) overall, with no heterogeneity between study design (p = 0.156). The overall estimate for heavy versus non/low drinkers was 1.12 (95% CI 0.87–1.45). The results were consistent according to selected study characteristics, including geographic area, definition of alcohol drinkers, and type of controls in case–control studies. Our findings provide evidence that alcohol drinking is not associated with endometrial cancer risk, although a weak positive association for very high drinkers cannot be excluded.     

Boiled coffee consumption and the risk of prostate cancer: follow-up of 224,234 Norwegian men 20–69 years

Background:

There is insufficient epidemiological evidence on the relationship between type of coffee and the risk of prostate cancer.

Methods:

The risk of prostate cancer by use of boiled vs not boiled coffee were assessed in a prospective study of 224,234 men 20–69 years. 5740 incident prostate cancers were identified.

Results:

With no coffee as reference group the hazard ratios of <1–4, 5–8 and 9+ cups per day of boiled coffee only were 0.84 (0.73–0.96), 0.80 (0.70–0.92) and 0.66 (0.55–0.80), P-trend=0.00. The corresponding figures for not boiled coffee were 0.89 (0.80–0.99), 0.91 (0.81–1.02) and 0.86 (0.74–1.00), P-trend=0.22.

Conclusion:

An inverse relationship between number of cups per day and the risk of prostate cancer was present only for the boiled coffee type.     

Case–control study of lifetime alcohol consumption and endometrial cancer risk

Purpose

Alcohol consumption is hypothesized to increase the risk of endometrial cancer by increasing circulating estrogen levels. This study sought to investigate the association between lifetime alcohol consumption and endometrial cancer risk.

Methods

We recruited 514 incident endometrial cancer cases and 962 frequency age-matched controls in this population-based case–control study in Alberta, Canada, from 2002 to 2006. Participants completed in-person interviews querying lifetime alcohol consumption and other relevant health and lifestyle factors. Participants reported the usual number of drinks of beer, wine, and liquor consumed; this information was compiled for each drinking pattern reported over the lifetime to estimate average lifetime exposure to alcohol.

Results

Lifetime average alcohol consumption was relatively low (median intake: 3.9 g/day for cases, 4.9 g/day for controls). Compared with lifetime abstainers, women consuming >2.68 and ≤8.04 g/day alcohol and >8.04 g/day alcohol on average over the lifetime showed 38 and 35 % lower risks of endometrial cancer, respectively (p trend = 0.023). In addition, average lifetime consumption of all types of alcohol was associated with decreased risks. There was no evidence for effect modification by body mass index, physical activity, menopausal status, and hormone replacement therapy use combined and effects did not differ by type of endometrial cancer (type I or II).

Conclusion

This study provides epidemiologic evidence for an inverse association between relatively modest lifetime average alcohol consumption (approximately 1/4 to 1/2 drink/day) and endometrial cancer risk. The direction of this relation is consistent with previous studies that examined similar levels of alcohol intake.     

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.