Nutrition and bladder cancer

Epidemiologic evidence on the relation between nutrition and bladder cancer is reviewed. A role of diet and nutrition in bladder carcinogenisis is plausible since most substances or metabolites, including carcinogens, are excreted through the urinary tract. Ecologic studies on populations have found positive correlations between fats and oils and bladder cancer, but these are reflected only partly in the international differences in bladder cancer rates, which are systematically higher in Europe than in the United States. Ten case-control and three cohort studies of bladder cancer published in English between 1979 and 1994, and including some information on dietary factors, were reviewed. Of seven studies which considered various types and measures of fruit and vegetable consumption, six found a reduced risk with increasing consumption, which was more consistent for vegetables, with relative risk (RR) estimates between 0.5 and 0.7 for the highest cf the lowest consumption level. There is, therefore, suggestive evidence that a diet rich in fresh fruit and vegetables is a correlate-or an indicator-of reduced bladder cancer risk. No clear association emerged for other foods investigated, including meat and milk. With reference to nutrients, total fat intake was related to bladder cancer risk in three case-control studies, with relative risks between 1.4 and 1.7 for the highest cf the lowest consumption level. However, no relationship between fats and bladder cancer emerged in c cohort study on Japneese-Americans in Hawaii. No consistent association emerged between protein or carbohydrate consumption and bladder cancer risk. Among micronutrients, vitamin A, and particularly carotenoids, showed an inverse association with bladder cancer risk in four case-control studies, including one allowing for a measure of total caloric intake, but were not related consistently in two other studies. There oere only scattered and inconclusive data on vitamin C and E. Finally, two studies suggested that calcium and sodium and sodium may be related to bladder cancer risk. Thus, available data on diet and bladder cancer are still inconclusive. This is at least partly attributable to the limited number of cohort studies and the paucity of case-control studies, including satisfactorily detailed and validated dietary questionnaires. Despite these limitations, available data suggest that a diet rich in fresh fruit and vegetables, and, hence, possibly in carotenoids, is a correlate of reduced bladder cancer risk.This work was conducted within the framework of the CNR (Italian National Research Council) Applied Project Clinical Applications of Oncological Research (Contracts No. 94.01321.PF39), and with the contributions of the Italian Association for Cancer Research and the Italian League Against Tumors, Milan.     

Nutrition and oral cancer

Epidemiologic evidence on the relationship between nutrition and oral cancer is reviewed. Ecologic and case-control studies provide most of the evidence regarding the nutritional epidemiology of oral cancer. The ecologic evidence is that the considerable geographic variation in the incidence of oral cancer is consistent with variation in nutrition. Because incipient oral cancer is likely to affect the diets of oral cancer patients, even before diagnosis, case-control studies are limited by their ability to extract comparable information from subjects regarding their pre-illness diets. The case-control evidence is that a diet that emphasizes fruit and vegetable intake may protect against oral cancer. However, this case-control evidence is not highly consistent; individual foods that appear protective in some studies do not in others, and the effects of diet appear to be modest when compared with those of smoking and alcohol consumption. The nutritional epidemiology of oral cancer is marked by two risk factors that appear far more powerful than nutrition: tobacco use and alcohol consumption. As these likely are related to nutrition, they pose as important potential confounders. Oral hygiene also may confound the association of nutrition and oral cancer risk; it is likely to be associated with dietary practice, and it has been shown to be related to oral cancer risk. Thus, studies of nutrition in the epidemiology of oral cancer also must address the effects of tobacco and alcohol consumption and oral hygiene.     

Nutrition and breast cancer

Epidemiologic evidence on the relation between nutrition and breast cancer is reviewed. After several decades of study, many aspects of the role of diet in breast cancer etiology are still unclear. Results from large prospective studies do not support the concept developed from animal and ecologic evidence that dietary fat intake in mid-life is associated with breast cancer risk. Thus, if fat intake is relevant to breast cancer, it is probably only at extremely low fat intakes or during early life. An emerging hypothesis that higher energy intake and growth rate in childhood and adolescence increases risk deserves further study. The possibility that diets rich in olive oil may be protective is also intriguing. Considerable evidence suggests that low intake of vegetables modestly increases the risk of breast cancer; however, the nutrients responsible remain elusive. The positive relation of alcohol intake with breast cancer risk has been seen repeatedly, and recently has been buttressed by studies showing that moderate alcohol intake increases estrogen endogenous levels. Advice to increase vegetable intake and limit alcohol consumption would probably have a modest, at best, effect on breast cancer risk. Future studies of the relation of nutrition during early life to subsequent breast cancer risk are needed.This work was supported, in part, by research grants CA 40456, CA 50598, and CA 55075 from the US National Institutes of Health, and a grant from the American Cancer Society (SIG-18). Dr Hunter is partially supported by a Faculty Research Scholar Award (FRA-455) from the American Cancer Society.     

Nutrition and esophageal cancer

Epidemiologic evidence on the relation between nutrition and esophageal cancer is reviewed. Results from ecologic, case-control, cohort, and intervention studies are included. Most of the findings pertain more to squamous cell carcinoma than adenocarcinoma of the esophagus. The protective effect of fruit and vegetable consumption is supported by a large body of evidence, especially from case-control studies. The effects of food groups and nutrients other than fruits and vegetables also have been examined, but the overall evidence is less convincing. Recent intervention studies in high incidence areas in China indicate that micronutrient supplements may have a modest effect in reducing risk, but the generalizability of this result is uncertain. Hot drinks are likelyto increase the risk of esophageal cancer. On the other hand, the role of tea drinking, especially the use of green tea, remains to be defined better.     

Nutrition and prostate cancer

Epidemiologic evidence on the relation between nutrition and prostate cancer is reviewed. Little is known about the etiology of prostate cancer, despite its prominence as the leading cancer among men in the United States. Rational mechanisms for dietary influences on prostate carcinogenesis, including effects on production or metabolism of androgenic hormones, have been proposed, but because few suitable animal models have been developed, the laboratory literature on diet and prostate cancer is sparse. Despite strong ecologic data and largely consistent case-control and cohort data on dietary fat and prostate cancer, the role of this nutrient remains unclear. Few studies, to date, have adjusted the results for caloric intake, and no particular fat component has been consistently implicated. A notable finding is a strong positive association with intake of animal products, especially red meats, but this in itself does not specifically implicate fat. Epidemiologic investigations on vitamin A and carotenoids are divided almost equally between studies showing postive and inverse associations. The evidence from these studies for a protective effect of fruits and vegetables on prostate cancer, unlike many other cancer sites, is not convincing. The data on other dietary components that have been examined with regard to prostate cancer etiology (cadmium, zinc, vitamins C and D, beverages, and legumes) are too incomplete at this time to draw any inferences as to their importance. The evidence for anthropometric associations with prostate cancer is weak. Whereas a clear association with obesity has not been shown, a positive relationship to muscle mass, though not yet established conclusively, further suggests the importance of androgens in this cancer.This project is funded partially by the National Cancer Institute grant nos. P01 CA 33619 and R01 CA 54281 from the US National Institutes of Health.     

Nutrition and laryngeal cancer

The main etiologic factors of cancers of the larynx and hypopharynx are alcohol and tobaeco, and their prevalence in different populations explains, to a large extent, the wide variations in incidence observed around the world. Besides these two main risk factors, however, diet also seems to play a role in determining the risk of these cancers. There is consistent evidence that low consumption of fruit and vegetables is associated with higher risk, after statistical adjustment for alcohol and tobacco. Consumption of vegetable oils and fish and a moderately high polyunsaturated/saturated fatty acid ratio (P/S ratio) were reported to be associated with reduced risk. Low intake of vitamin C, -carotene and vitamin E were reported consistently to be associated with higher laryngeal cancer risk, but there was no clear evidence that these micronutrients are better predictors of cancer risk than the principal food groups from which their intake levels were estimated, i.e., fruits, vegetables, vegetable oils, and fish. Given the overwhelming role of tobacco and alcohol in the etiology of these cancers and the extremely low incidence among nonsmokers/nondrinkers, the available studies provide no estimate of the role of diet in subjects not exposed to these factors. The evidence indicates, however, that, in the presence of tobacco and/or alcohol, low intake of fruit and vegetables may account for 25 to 50 percent of the cases among men.     

Nutrition and cervical neoplasia

Epidemiologic evidence on the relation between nutrition and cervical cancer is reviewed. Cervical cancer is the leading cancer among women in many developing countries, and remains a major public health problem worldwide. This review of nutritional research on cervical neoplasia encompasses the range of epithelial abnormalities from early preneoplastic lesions to invasive cancer. Identified risk factors for cervical neoplasia suggest a multifactorial etiology with several cancer-associated human papillomaviruses (HPV) as the central cause. Studies of nutritional predictors of cervical neoplasia to date, however, have been limited by inadequate HPV measures, which compromise the interpretations of findings. Current research using accurate measures of HPV will be most revealing. Nonetheless, agreement in findings from previous studies suggest a role for nutritional factors in some or all stages of cervical neoplasia. Low vitamin C and carotenoid status are associated fairly consistently with both cervical cancer and precursors, whereas results for vitamin E status are less consistent. The effect of folate status may be restricted to early preneoplastic cervical lesions and not to more advanced disease. Current research is addressing nutritional influences on HPV infection and persistence and on progression of cervical disease. Limitations and recommendations for future research directions are discussed in light of methodologic issues related to nutritional and HPV research.     

Nutrition and lung cancer

Epidemiologic evidence on the relationship between nutrition and lung cancer is reviewed. Observational studies of diet and lung cancer, both prospective and retrospective, continue to suggest strongly that increased vegetable and fruit intake is associated with reduced risk in men and women; in various countries; in smokers, ex-smokers, and never-smokers; and for all histologic types of lung cancer. Prospective studies of blood -carotene levels, arguably the best available biomarker of vegetable and fruit intake, indicate that low levels are predictive of increased lung cancer incidence. However, in a randomized, placebo-controlled clinical trial in male smokers, lung cancer incidence and total mortality were increased significantly among the men receiving -carotene supplements. If -carotene can prevent lung carcinogenesis, which the trial cannot rule out, then the dosage, duration of use, method of administration, and/or subpopulation are critical. Ongoing clinical trials, some of which include women, will provide much-needed information. Other carotenoids, other phytochemicals, and associated dietary patterns may explain the beneficial effects of vegetables and fruits and have not been explored adequately in epidemiologic work. Several observational epidemiologic studies, both prospective and retrospective, have indicated that diets high in fat, saturated fat, and cholesterol may increase the risk of lung cancer and that the effect is not mediated through vegetable and fruit intake. The relationship, although not yet established, merits further investigation. Since -carotene can function as an antioxidant, other micronutrients with this potential, specifically vitamins E and C and selenium, also have been proposed to reduce lung cancer risk. However, the totality of the epidemiologic evidence is not, at present, persuasive for any one of these micronutrients.     

Tumor TP53 expression status, body mass index and prognosis in colorectal cancer

Inactivation of the TP53 (p53) pathway by TP53 mutations is one of key steps in colorectal carcinogenesis. TP53 also plays an important role in cellular energy metabolism. We hypothesized that TP53-altered tumor cells might behave aggressively independent of energy balance, while progression of TP53-intact cells might depend on excess energy balance. Utilizing a database of 1,060 colon and rectal cancer patients in two prospective cohort studies, we evaluated TP53 expression by immunohistochemistry. Among 1,060 colorectal cancers, 457 (43%) tumors were positive for TP53. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, the CpG island methylator phenotype, LINE-1 methylation, KRAS, BRAF and PIK3CA. TP53 positivity was not significantly associated with cancer-specific survival in univariate analysis with HR of 1.16 [95% confidence interval (CI)=0.92-1.45], which became significant after stage adjustment (multivariate HR=1.30; 95% CI=1.02-1.65). Notably, we found a possible modifying effect of patient's body mass index (BMI) on tumor TP53. In non-obese patients (BMI<30 kg/m2), TP53 positivity was associated with shorter cancer-specific survival (multivariate HR=1.53; 95% CI=1.17-2.00), while TP53 positivity was not significantly associated with survival among obese patients (BMI≥30 kg/m2). Effect of TP53 positivity on cancer-specific survival significantly differed by BMI (pinteraction=0.0051). The adverse effect of obesity on patient mortality was limited to TP53-negative patients. These molecular pathological epidemiology data may support a dual role of TP53 alterations in cell-cycle deregulation and cell autonomy with respect to energy balance status.     

Diet, lifestyle and risk of K-ras mutation-positive and -negative colorectal adenomas

K-ras mutation-positive (K-ras+) and -negative (K-ras-) colorectal adenomas may differ clinically and pathologically. As environmental compounds may cause mutations in the growth-related K-ras oncogene or affect clonal selection depending on mutational status, we evaluated whether the aetiology of K-ras+ and K-ras- adenomas differs. K-ras mutations in codons 12 and 13 were assessed in colorectal adenoma tissue (K-ras+: n = 81, K-ras-: n = 453). Dietary and lifestyle data were collected through questionnaires that were also administered to 709 polyp-free controls. Multiple logistic regression analyses showed that intake of vitamin B2 and monounsaturated fat were differently associated with risk of K-ras+ and K-ras- adenomas; vitamin B2 was inversely associated with K-ras- (highest vs. lowest tertile: odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.50-0.97, p trend = 0.020), but not with K-ras+ adenomas, and a positive association with monounsaturated fat was confined to K-ras- adenomas (OR = 1.57, 95% CI = 1.06-2.34, p trend = 0.029). Besides, potential, not statistically significant, differences in risk arose because red meat was distinctly positively associated with K-ras+ adenomas (OR = 1.70, 95% CI = 0.94-3.09, p trend = 0.061); total dietary and polyunsaturated fat tended to be inversely associated with risk of K-ras+ but not of K-ras- adenomas; inverse associations with dairy products, calcium, protein and tea were confined to K-ras- adenomas, and smoking was more markedly positively associated with K-ras- adenomas. No differences in risk of K-ras+ and K-ras- adenomas could be detected for other factors. In conclusion, dietary and lifestyle factors may influence risk of K-ras+ and K-ras- adenomas differently. However, epidemiological literature on diet, lifestyle and colorectal K-ras mutations is inconsistent.     

Nutrition and endometrial cancer

Epidemiologic evidence on the relation between nutrition and endometrial cancer (EC) is reviewed. Obesity is an important determinant of EC, probably because of its effect on the hormonal milieu of both pre-and postmenopausal women. However, epidemiologic studies of body fat distribution and EC are inconsistent, as are the data pertaining to the relation between body fat distribution and sex hormones. Randomized and observational studies of diet and sex hormones indicate that low fat diets may be associated weakly with decreased estrogen levels, and thus a lowering of EC risk. Only ecologic and case-control studies of diet and EC have been reported. These finding as well as the methodologic limitations of these study designs are discussed. Both types of studies implicate fat as a potential risk factor, while the case-control studies suggest that carotene may lower risk of EC. Epidemiologic studies of alcohol and EC also are inconsistent, but generally indicate no association, or a weak protective effect. The role of diet in the etiology of EC is unresolved. The conduct of cohort and intervention studies, which can avoid many of the methodologic shortcomings of ecologic and case-control studies, would improve our understanding of diet and EC.Address correspondence to Dr Hill.     

Nutrition and renal cell cancer

Epidemiologic evidence on the relation between nutrition and renal cell cancer is reviewed. Kidney cancer, comprising 1.7 percent of all malignant diseases diagnosed worldwide, shows about a 20-fold international variation in the incidence in men and 10-fold in women. This substantial variation indicates an important causal role of environmental factors. Renal cell (parenchymal) cancer (RCC) accounts for about 80 percent of all kidney cancers. While the etiology of RCC is incompletely understood, analytic epidemiologic studies provide consistent support for a positive association of obesity with risk of RCC; the dose-response observed supports a causal relationship. Only a few prospective studies, all of them limited in size, have been published, while ecologic and case-control studies suggest that diet may be important in the etiology of RCC. However, contradictory results and methodologic limitations in some casecontrol studies prevent definite conclusions concerning diet and RCC. A positive association of protein and fat intake, as well as their main food sources (meat, milk, fats), with risk of RCC-as suggested by ecologic studies—has no clear support in analytic epidemiologic studies. A protective effect of vegetables and fruits has been observed in most casecontrol studies, while the majority do not show an association between alcohol, coffee, and risk of RCC. Recent reports indicated an increased risk of RCC associated with consumption of fried/sautéed meat and low intakes of magnesium or vitamin E. An apparent positive association with total energy intake, perhaps due to bias, needs further investigation.This project was funded partially by the Swedish Cancer Society.     

Yogurt consumption and risk of colorectal cancer in the Italian European prospective investigation into cancer and nutrition cohort

Fermented dairy products like yogurt have been suggested to protect against colorectal cancer (CRC). We conducted a prospective study on 45,241 (14,178 men; 31,063 women) volunteers of the EPIC-Italy cohort who completed a dietary questionnaire including specific questions on yogurt intake. During 12 years of follow-up, 289 volunteers were diagnosed with CRC. Hazard ratios (HRs) for the disease and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models, stratified by dietary questionnaire and adjusted for energy intake and other potential confounders. Yogurt intake was inversely associated with CRC risk. For the energy-adjusted model, HR for CRC in the highest versus lowest tertile of yogurt intake was 0.62 (95% CI, 0.46-0.83). In the full model adjusted for energy, simple sugar, calcium, fiber, animal fat, alcohol and red meat intake, as well as body mass index, smoking, education and physical activity, HR was 0.65 (95% CI, 0.48-0.89) in the highest versus lowest tertile. The protective effect of yogurt was evident in the entire cohort, but was stronger in men, although there was no interaction of sex with the yogurt-CRC association (p(interaction) 0.20, fully adjusted model). In our prospective study, high yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease. Investigation of larger cohorts is necessary to reveal any residual confounding of the association of yogurt intake with CRC risk.     

Hereditary colorectal cancer syndromes

The purpose of this article is to review the genetic colorectal cancer syndromes including Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Family Polyposis (FAP) and the hamartomatous polyposis syndromes. HNPCC is the most common of the hereditary colorectal cancer syndromes, and is the result of defects in the mismatch repair genes. Individuals with HNPCC have an 80 lifetime risk of colorectal cancer, and in females a 30–50% risk of endometrial cancer, as well as predisposition for a number of other malignancies. Early screening and interval surveillance for colorectal and endometrial cancer are recommended. In FAP, mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene give rise to hundreds to thousands of colorectal polyps, some of which will inevitably progress to cancer. Early diagnosis and timely prophylactic colectomy prevent this outcome. Chemoprevention with nonsteroidal anti-inflammatory drugs can reduce adenoma number and size in FAP, but the effect is incomplete. In addtion, surveillance for upper gastrointestinal tract malignancies is necessary. Attenuated forms of FAP may be the result of mutations in the APC gene, or in the recently described MYH gene. Mutations in the MYH gene should be considered in individuals with multiple adenomas whose family history does not reflect an autosomal dominant pattern of inheritance. The hamartomatous polyposis syndromes are uncommon but distinctive disorders in which multiple hamartomatous polyps develop at a young age. Our understanding of the genetic basis of these disorders is improving, and a predisposition for gastrointestinal and other malignancies has recently been recognized. This article summarizes the genetics, clinical manifestations and clinical management of each of these syndromes with an emphasis on genetic testing and prevention.     

Epidemiology and risk factors of colorectal cancer in China

In China, colorectal cancer(CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first worldwide in the number of new CRC cases and CRC-related deaths because of its comparatively large population. This disease represents a threat to the health of population and incurs a heavy economic burden on the society and individuals. CRC has various risk factors, including age, se...     

The role of the barium enema in the diagnosis of colorectal neoplasia

The recent interest in guidelines for colorectal cancer diagnosis, management and in screening has important implications for radiologists. The present article reviews the role of the barium enema in colorectal neoplasia diagnosis in symptomatic patients, and in the context of screening programmes.     

Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study

Background:

Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS).

Methods:

We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up.

Results:

Among 57 851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506 930 years (SIR, 1.14 (95% confidence interval (CI): 1.03–1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52–0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48–10.75) for colon cancer and 4.81 (95% CI: 2.85–7.60) for rectal cancer. Thereafter, the SIRs declined and 4–10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95.

Conclusion:

We found a decreased risk of colorectal cancer in the period 1–10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.     

Social disparities across the continuum of colorectal cancer: a systematic review

Objective:The purpose of this review is to evaluate the published literature to assess social inequalities in colorectal cancer using the cancer disparities grid. Methods: Three computerized databases were searched from January 1990 to January 2004 to identify published English language articles that collected data from study participants living in the United States. Abstracts were reviewed and articles that dealt with social inequality and colorectal cancer were selected. A total of 46 articles were identified and classified into the appropriate cell of the cancer disparities grid. Results: The majority of research identified for the grid has focused primarily in one domain of inequality, race/ethnicity and racism, and within one column of the cancer continuum, cancer screening. About one-third of the articles focused on multiple aspects of social inequalities. There were few or no published research articles within many of the domains of social inequality along the continuum of colorectal cancer prevention, treatment, and outcomes. Conclusions: This review found only a modest amount of research has been conducted that has examined the influence of social inequalities on colorectal cancer. Findings suggest that a multidisciplinary approach is needed to measure and remedy these social inequalities.Address correspondence to: Richard C. Palmer, DFCI-CCBR, 44 Binney Street, Smith 272, Boston, MA 02115, USA; Ph.: 617-632-4223; Fax: 617-632-3161; e-mail: richard_palmer@dfci.harvard.edu