Meat consumption and colorectal cancer: a review of epidemiologic evidence

This article reviews the epidemiologic evidence on colorectal cancer risk and meat consumption from 32 case-control and 13 cohort studies published in English from 1970 to 1999 and retrieved from the Medline database. The results support the hypothesis that meat consumption is associated with a modest increase in colorectal cancer risk. This association, however, seems to have been more consistently found for red meat and processed meat. The studies on cooking methods and meat "doneness" are not consistent and the evidence is not conclusive.     

Diet,body weight,and colorectal cancer: a summary of the epidemiologic evidence

Colorectal cancer is the second leading cause of cancer death in the United States, and the number of new cases annually is approximately equal for men and women. Several nutritional factors are likely to have a major influence on risk of this cancer. Physical inactivity and excessive adiposity, especially if centrally distributed, clearly increase the risk of colon cancer. Hyperinsulinemia may be an important underlying risk factor. In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents. Currently, the evidence is strongest for folate and calcium. Folate may be especially important in alcohol drinkers because alcohol appears to increase the risk, particularly when folate intake is low. This interaction may be related to the antifolate properties of alcohol. In contrast to earlier studies, more recent epidemiologic studies have generally not supported a strong influence of dietary fiber or fruits and vegetables, although these have other health benefits, and their consumption should be encouraged. The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.     

Polypropylene production and colorectal cancer: a review of the epidemiological evidence

Polypropylene has been produced for over 35 years and has awide variety of applications including industrial uses, foodpackaging and many domestic uses. As a high-molecular-weightpolymer, polypropylene is considered chemically inert with littleor no physiological or toxicological effects. Nevertheless,early epidemiological studies of polypropylene production workersand carpet manufacturing employees who use polypropylene reporteda significant excess of colorectal cancer. In one study, fiveof the seven cases were diagnosed within a five-month period,and in the other study, five cases were diagnosed within an18-month period. Recent updates of these two study populationshave found no continuation of the excess of colorectal cancer,thereby indicating that the earlier observations on these twogroups reflected the chance nature of a time-space cluster.Moreover, investigations of polypropylene production workersin the United States, Germany, Australia and the United Kingdomfound no association with colorectal cancer. When the resultsof all studies of polypropylene production workers are pooled,the summary risk ratio for colorectal cancer is 1.37 (95% confidenceinterval 0.83–2.11). Taken together, the epidemiologicalevidence and the absence of toxicological data do not supporta causal association between polypropylene and colorectal cancer.     

Trichloroethylene and cancer: systematic and quantitative review of epidemiologic evidence for identifying hazards

We conducted a meta-analysis focusing on studies with high potential for trichloroethylene (TCE) exposure to provide quantitative evaluations of the evidence for associations between TCE exposure and kidney, liver, and non-Hodgkin lymphoma (NHL) cancers. A systematic review documenting essential design features, exposure assessment approaches, statistical analyses, and potential sources of confounding and bias identified twenty-four cohort and case-control studies on TCE and the three cancers of interest with high potential for exposure, including five recently published case-control studies of kidney cancer or NHL. Fixed- and random-effects models were fitted to the data on overall exposure and on the highest exposure group. Sensitivity analyses examined the influence of individual studies and of alternative risk estimate selections. For overall TCE exposure and kidney cancer, the summary relative risk (RRm) estimate from the random effects model was 1.27 (95% CI: 1.13, 1.43), with a higher RRm for the highest exposure groups (1.58, 95% CI: 1.28, 1.96). The RRm estimates were not overly sensitive to alternative risk estimate selections or to removal of an individual study. There was no apparent heterogeneity or publication bias. For NHL, RRm estimates for overall exposure and for the highest exposure group, respectively, were 1.23 (95% CI: 1.07, 1.42) and 1.43 (95% CI: 1.13, 1.82) and, for liver cancer, 1.29 (95% CI: 1.07, 1.56) and 1.28 (95% CI: 0.93, 1.77). Our findings provide strong support for a causal association between TCE exposure and kidney cancer. The support is strong but less robust for NHL, where issues of study heterogeneity, potential publication bias, and weaker exposure-response results contribute uncertainty, and more limited for liver cancer, where only cohort studies with small numbers of cases were available.     

Folate and colorectal cancer – a review of the current evidence

Summary  Colorectal cancer is the second most common tumour in the United Kingdom. Migration studies suggest that environmental factors, particularly diet, account for the wide variation in worldwide incidence of the disease. Prospective cohort studies have shown that diets low in meat and high in vegetables decrease risk. Folate is thought to account partly for the protection conferred by high intakes of vegetables, since it plays a crucial role in maintaining genomic stability, being required in two important processes, DNA synthesis and methylation. The public health implications of existing evidence supporting a reduction in neural tube defects, ischaemic heart disease and possibly cancer fuel the nationwide folate fortification debate, while ever progressing nutritional genomic technology promises a greater understanding of the mechanisms underlying the relationship between folate and colorectal cancer risk.     

Maternal caffeine consumption and spontaneous abortion: a review of the epidemiologic evidence

Since the 1980s, numerous studies have investigated whether caffeine intake during pregnancy affects the risk of spontaneous abortion. A clear consensus, however, has not been reached. Because of the public health importance of this question, we reviewed the results of 15 epidemiologic studies on this topic, with particular attention to the specific methodologic problems that would generate biased findings. These include selection and recall bias, confounding, several issues pertaining to exposure measurement, and the failure to account for fetal karyotype, caffeine metabolism, the timing of fetal demise, and the possibility that an effect of caffeine may be gestational age-specific. All of the studies reviewed suffer from important methodologic limitations that hinder both the interpretation of each study individually and the comparison of results across studies. Despite the fact that most epidemiologic studies have observed a positive association between maternal caffeine intake and the risk of spontaneous abortion, we conclude that the evidence must be considered to be equivocal, given the biases likely present and the fact that most of the potential biases would tend to overestimate any association. Until studies can overcome these limitations, evidence for a causal link between caffeine and spontaneous abortion will remain inconclusive.     

Arsenic exposure and cardiovascular disease: a systematic review of the epidemiologic evidence

Arsenic exposure is a likely cause of blackfoot disease and a potential risk factor for atherosclerosis. The authors performed a systematic review of the epidemiologic evidence on the association between arsenic and cardiovascular outcomes. The search period was January 1966 through April 2005. Thirteen studies conducted in general populations (eight in high-arsenic areas in Taiwan, five in other countries) and 16 studies conducted in occupational populations were identified. Exposure was assessed ecologically in most studies. In Taiwan, relative risks comparing the highest arsenic exposure category with the lowest ranged from 1.59 to 4.90 for coronary disease, from 1.19 to 2.69 for stroke, and from 1.66 to 4.28 for peripheral arterial disease. In other general populations, relative risks ranged from 0.84 to 1.54 for coronary disease, from 0.69 to 1.53 for stroke, and from 0.61 to 1.58 for peripheral arterial disease. In occupational populations, relative risks ranged from 0.40 to 2.14 for coronary disease mortality and from 0.30 to 1.33 for stroke mortality. Methodologic limitations, however, limited interpretation of the moderate-to-strong associations between high arsenic exposure and cardiovascular outcomes in Taiwan. In other populations or in occupational settings, the evidence was inconclusive. Because of the high prevalence of arsenic exposure, carefully performed studies of arsenic and cardiovascular outcomes should be a research priority.     

A review of epidemiologic evidence that carotenoids reduce the risk of cancer

The epidemiologic evidence that carotenoids are involved in cancer etiology is evaluated. Low intake of vegetables and fruits and carotenoids is consistently associated with an increased risk of lung cancer in both prospective and retrospective studies. In addition, low levels of serum or plasma beta-carotene are consistently associated with the subsequent development of lung cancer. The simplest explanation is that beta-carotene is indeed protective. Since retinol is not related in a similar manner to lung cancer risk, beta-carotene seems to play a role that does not require its conversion into vitamin A. However, the importance of other carotenoids, other constituents of vegetables and fruits, and other nutrients whose levels in the blood are partially correlated with those of beta-carotene has not been adequately explored. In addition, smoking, a powerful risk factor for lung cancer, is associated with reduced intake of carotenoids and lowered blood levels of beta-carotene and has not always been adequately controlled in these analyses. Prospective and retrospective studies suggest that carotenoids may reduce the risk of certain other cancers; however, too few studies have looked at these sites to examine the consistency of the evidence. Although clinical trials of the efficacy of beta-carotene in cancer prevention are underway, it is still necessary and prudent to continue well-designed prospective and retrospective studies of the carotenoid hypothesis.     

Foodstuffs and colorectal cancer risk: a review

BACKGROUND AND AIMS: To assess the relationships between food intake and colorectal cancer risk. METHODS: Systematic review of available prospective studies on dietary intake and colorectal cancer. RESULTS: Twelve out of 15 studies found no significant relationship between vegetable intake and colorectal cancer risk; also, 11 out of 14 studies found no relationship with fruit consumption. Conversely, the combined consumption of vegetables and fruit reduced colorectal cancer risk in three out of six studies, although the relationship was somewhat inconsistent between genders and anatomical localizations. Most studies found no relationship between cancer risk and red meat (15 in 20) or processed meat (seven out of 11) consumption; still, most of the reported relative risks were above unity, suggesting that high consumption of red or processed meat might increase colorectal cancer risk. The consumption of white meat, fish/seafood, dairy products, coffee or tea was mostly unrelated to colorectal cancer risk, although the consumption of smoked or salted fish actually increased risk. CONCLUSIONS: The relationships between dietary intake and colorectal cancer risk might be less important than previously reported. The combined consumption of vegetables and fruit might be protective, whereas excessive consumption of meat or smoked/salted/processed food appears to be deleterious.     

Dichlorodiphenyldichloroethane burden and breast cancer risk: a meta-analysis of the epidemiologic evidence

The relationship of dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk has received increasing attention since the beginning of the 1990s. Contradicting published results regarding the relationship between body burden levels of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE)--the main DDT metabolite--and breast cancer, we argue that such differences stem from methodologic differences among those studies. We performed a meta-analysis of 22 articles using DerSimonian and Laird's method for random effects models. The Q-statistic was used to identify heterogeneity in the outcome variable across studies. The gradient of p,p'-DDE exposure in epidemiologic studies was homogenized to serum lipid bases (nanograms per gram). The potential for publication bias was examined by means of the Begg's test. We discuss methodologic features of the studies in an attempt to reconcile the findings. The summary odds ratio (OR) for selected studies was 0.97 (95% confidence interval, 0.87-1.09) and the gradient of exposure ranged from 84.37 to 12,948 ng/g. No overall heterogeneity in the OR was observed (chi-squared = 27.93; df = 23; p = 0.218). Neither the study design nor the lack of breast-feeding control or the type of biologic specimen used to measure p,p'-DDE levels were the causes of heterogeneity throughout the studies. Evidence for publication bias was not found (p = 0.253). Overall, these results should be regarded as a strong evidence to discard the putative relationship between p,p'-DDE and breast cancer risk. Nevertheless, the exposure to DDT during critical periods of human development--from conception to adolescence--and individual variations in metabolizing enzymes of DDT or its derivatives are still important areas to be researched in regard to breast cancer development in adulthood.     

Particulate air pollution and fetal health: a systematic review of the epidemiologic evidence

BACKGROUND: Research on the potential impact of air pollution on the health of adults and children has grown rapidly over the last decade. Recent studies have suggested that air pollution could also be associated with adverse effects on the developing fetus. This systematic review evaluates the current level of epidemiologic evidence on the association between ambient particulate air pollution and fetal health outcomes. We also suggest further research questions. METHODS: Using database searches and other approaches, we identified relevant publications published between 1966 and 2001 in English. Articles were included if they reported original data on birthweight, gestational age at delivery, or stillbirth related to directly measured nonaccidental exposure to particulate matter. RESULTS: Twelve studies met the inclusion criteria. There was little consistency in the evidence linking particulate air pollution and fetal outcomes. Many studies had methodologic weaknesses in their design and adjustment for confounding factors. Even in well-designed studies, the reported magnitude of the effects was small and inconsistently associated with exposure at specific stages of pregnancy. CONCLUSIONS: The currently available evidence is compatible with either a small adverse effect of particulate air pollution on fetal growth and duration of pregnancy or with no effect. Further research should be directed toward clarifying and quantifying these possible effects and generating testable hypotheses on plausible biologic mechanisms.     

Quality of life and colorectal cancer: a review

OBJECTIVES: To describe what is known of quality of life for colorectal cancer patients, to review what has been done in the Australian setting and to identify emerging directions for future research to address current gaps in knowledge. METHOD: A literature search (using Medline, Psychinfo, CINAHL and Sociological Abstracts) was conducted and 41 articles identified for review. RESULTS: Three key areas relating to quality of life in colorectal cancer patients emerged from the literature review: the definition and measurement of quality of life; predictors of quality of life; and the relationship of quality of life to survival. Results of existing studies are inconsistent in relation to quality of life over time and its relationship to survival. Small sample sizes and methodological limitations make interpretation difficult. CONCLUSIONS: There is a need for large-scale, longitudinal, population-based studies describing the quality of life experienced by colorectal cancer patients and its determinants. Measurement and simultaneous adjustment for potential confounding factors would productively advance knowledge in this area, as would an analysis of the economic cost of morbidity to the community and an assessment of the cost effectiveness of proposed interventions. IMPLICATIONS: As the Australian population ages, the prevalence of colorectal cancer within the community will increase. This burden of disease presents as a priority area for public health research. An improved understanding of quality of life and its predictors will inform the development and design of supportive interventions for those affected by the disease.     

Dietary patterns and metabolic syndrome--a review of epidemiologic evidence

Metabolic syndrome is associated with increased risk of coronary heart disease and type 2 diabetes, and appears to be widely prevalent in both developed and developing countries. While lifestyle modification is recommended for management of the syndrome, the dietary pattern most beneficial for patients is yet to be ascertained. Original research papers from the Medline database were examined for dietary patterns that may be associated with the syndrome. Three large-scale epidemiological studies were found fitting our criteria. Dietary patterns high in fruit and vegetable content were generally found to be associated with lower prevalence of metabolic syndrome. Diet patterns with high meat intake were frequently associated with components of metabolic syndrome, particularly impaired glucose tolerance. High dairy intake was generally associated with reduced risk for components of metabolic syndrome with some inconsistency in the literature regarding risk of obesity. Minimally processed cereals appeared to be associated with decreased risk of metabolic syndrome, while highly processed cereals with high glycaemic index are associated with higher risk. Fried foods were noticeably absent from any dietary pattern associated with decreased prevalence of metabolic syndrome. The conclusion of this review is that no individual dietary component could be considered wholly responsible for the association of diet with metabolic syndrome. Rather it is the overall quality of the diet that appears to offer protection against lifestyle disease such as metabolic syndrome. Further research is required into conditions, such as overweight and obesity, which may influence the effect of diet on the development of metabolic syndrome.     

N-acetyltransferase polymorphisms and colorectal cancer: a HuGE review

The two expressed genes coding for N-acetyltransferase (NAT) activity, NAT1 and NAT2, are located on chromosome 8 at 8p21.3-23.1 and are polymorphic. Both enzymes are capable of N-acetylation, O-acetylation, and N,O-acetylation and are implicated in the activation and detoxification of known carcinogens. Single base-pair substitutions in NAT2 tend to occur in combination with other substitutions within the gene. As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the reported polymorphisms exist. It is important to select a method that is appropriate to the population being studied. The functional significance of many NAT allelic variants has not been determined. Geographic and ethnic variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern. No consistent association has been found between acetylator phenotype or genotype and colorectal cancer. The lack of consistency can in part be accounted for by methodological factors, including limited statistical power. Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.     

A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies

Objective

To systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent “weight-of-evidence” (WOE) methodological approach.

Methods

Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. The AHS evaluated pesticide applicators as well as dose–response associations for specific pesticide compounds, whereas the large majority of non-AHS evaluated applicators but did not analyze specific compounds or dose–response trends. This WOE assessment of 153 different pesticide–outcome pairs emphasized several key evidentiary features: existence of statistically significant relative risks, magnitude of observed associations, results from the most reliable exposure assessments, and evidence of convincing dose–response relationships (i.e., those monotonically increasing, with statistically significant trend tests).

Results

Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Deficits of colon or rectal cancer were observed across most studies of pesticide applicators. After applying the WOE methodology to the epidemiologic studies of specific pesticide compounds and colon or rectal cancer, a number of pesticide–outcome pairs were identified and evaluated further based on positive statistical associations. Of these, only two—aldicarb and colon cancer and imazethapyr and proximal colon cancer—appears to warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose–response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk.

Conclusion

The available epidemiologic evidence does not support a causal relationship between occupation as a pesticide applicator or specific pesticide exposures and colon or rectal cancer.     

Nightshift work and risk of breast cancer and other cancers--a critical review of the epidemiologic evidence

OBJECTIVES: This systematic review concerns the role of nightshift work in the risk of breast cancer or other cancers. METHODS: Studies that specifically included information on nightshift or shift work and reported cancer occurrence were focused upon. A systematic search of Medline and the Science Citation Index was conducted until May 2007. The quality of each paper was discussed with respect to design, exposure and outcome information, bias, confounding, and exposure-response assessment. RESULTS: Thirteen relevant reports were found, and eight reported the relative risk for breast cancer, three for prostate cancer, three for colon cancer, and four for all cancers. Most of the studies had crude information about nightshift work, four register-linked studies had no individual exposure information but relied on exposure probabilities assessed on a group level, and no studies analyzed cancer risk according to the cumulative number of night shifts (however, most of the studies did so according to the number of years of nightshift work). Confounding did not seem to be of major concern. The presentation of the results was not always complete, and it would have been appreciated if the reasons for leaving some findings out had been reported. There were indications of a long-term effect of nightshift work (more than 20-30 years), but the number of positive studies was small. In addition, they were all conducted among nurses, and the risk estimates were only moderately increased. This situation makes the results sensitive to bias, chance, and confounding. CONCLUSIONS: There is limited evidence for a causal association between nightshift work and breast cancer, while there is insufficient evidence for prostate cancer, colon cancer, and overall cancer.     

Childhood cancer in relation to cured meat intake: review of the epidemiological evidence.

Over the past two decades a series of epidemiological studies have examined the relationship between consumption of cured meats during pregnancy and the subsequent risk of brain tumors, as well as other cancers, in the offspring. The research was prompted in large part by experimental investigations showing that transplacental exposure to certain N-nitroso compounds, i.e., nitrosoureas, could produce brain tumors in laboratory animals. Fourteen such epidemiological studies, 13 of which used the case-control approach, are reviewed here. Most of the studies showed no significant association between total cured meat intake and childhood cancer risk but more found positive than negative relationships. Furthermore, several studies reported significant positive associations for maternal and sometimes childhood or paternal consumption of one or more cured meats, with odds ratios of twofold or greater reported among the highest consumers. On the other hand, a correlation analysis found no positive concordance between temporal trends from the 1970s to 1990s in childhood brain cancer rates and cured meat consumption, inasmuch as cancer rates rose over time while residual nitrite levels in cured meats fell sharply. Because of the potential for bias, especially recall bias, and/or confounding, the relatively weak magnitude of the associations reported, and the inconsistency between study findings, at this time it cannot be concluded that eating cured meat has increased the risk of childhood brain cancer or any other cancers. Moreover, although N-nitroso compounds are sometimes found in cured meats or may be formed endogenously, there is no empirical evidence that eating cured meats results in human neural nitrosourea exposure. Nevertheless, the hypothesis that eating nitrite-cured meats may influence childhood and perhaps adult brain cancer cannot be dismissed. Unbiased evaluation of the hypothesis may derive from the conduct of cohort studies, where the interview-derived information on cured meat intake precedes, or is not otherwise associated with, the diagnosis of cancer.