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 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.     

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.     

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 colorectal cancer

Epidemiologic evidence on the relation between nutrition and colorectal cancer is reviewed. Colon cancer varies approximately 20-fold internationally. Although there is clear evidence of genetic predisposition to colon cancer, much of this variation appears to be related to differences in dietary habits. At present, the data suggest that vegetables are associated with lower risk, and that fiber alone does not account for this association. Further, meat consumption is associated with increased risk but this, too, is not explained solely by its fat content. Several microconstituents of the diet may be associated with reduced risk-including folate and calcium-but phytochemicals of other sorts may be relevant. Mutagenic compounds, particularly heterocyclic amines, produced when protein is cooked, plausibly explain the meat association. The most consistent inverse association is with physical activity. Alcohol is associated, though inconsistently, with increased risk. Rectal cancer is less well studied but, at present, there are few data to suggest that the dietary risk factors are markedly different. Physical activity does not appear to be associated with a lower risk. Colorectal adenomatous polyps also appear to share the spectrum of risk factors seen with colon cancer, although, for adenomas, tobacco smoking is also c clear and consistent risk factor. There are a variety of links between the dietary epidemiology and physiology of colorectal neoplasia and the relevant pathogigic and molecular changes. Other causal connections remain to be explicated.Address correspondence to Dr Potter, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104, USA.     

Combined surgery and postoperative radiation therapy for advanced laryngeal and hypopharyngeal carcinomas

The survival, pattern of failure and complications in 47 patients with Stage III and IV cancers of the glottis, supraglottis and hypopharynx treated with surgery and postoperative radiotherapy using a new treatment technique referred to as "mini-mantle" were analyzed. The absolute survival probability of the entire group was 53 and 31% at 3 and 5 years. The local control probability at 3 and 5 years was 63 and 58%, and was higher for the supraglottic/hypopharyngeal than for glottic carcinomas. Advanced lesions, lymph node metastases and positive resection margins were significantly related to a worse local control. Five patients developed complications requiring surgical correction, but none experienced mortality. Moderate complications were treated conservatively without lasting sequelae. This technique is a reasonably safe and efficient procedure and can be effectively employed for the management of advanced laryngeal and hypopharyngeal carcinomas after definitive surgery.     

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.     

Occupation and larynx and hypopharynx cancer: a job-exposure matrix approach in an international case-control study in France,Italy, Spain and Switzerland

Objective: To investigate the effect of exposure to occupational agents on the risk of hypopharyngeal/laryngeal cancer. Methods: Case-control study conducted during 1979–1982 in six centres in South Europe. An occupational history and information on exposure to non-occupational factors were collected for 1010 male cases of hypopharyngeal/laryngeal cancer as well as for 2176 population controls. The exposure to 10 occupational agents was assessed through a job-exposure matrix. As occupational histories had been collected since 1945 major analyses were restricted to subjects aged less than 55 years (315 cases and 819 controls). Results: Significant elevated risks adjusted for non-occupational variables (smoking, alcohol consumption and diet) and other occupational exposures were consistently found for organic solvents (odds ratio (OR) for ever-exposure: 1.7, 95% confidence interval: 1.1–2.5) and asbestos (OR: 1.6, 1.0–2.5). A significant positive trend for both probability of exposure and duration was found for exposure to solvents. A positive association between exposure to formaldehyde and laryngeal cancer was also suggested. No association was found for exposure to arsenic and compounds, chromium and compounds, and polycyclic aromatic hydrocarbons. Analyses restricted to subjects aged 55 or more did not show elevated risks, with the exception of wood dust (OR: 1.8, 1.3-2.7). Conclusions: In our study occupational exposure to solvents was associated with an increased risk of hypopharyngeal/laryngeal cancer. Results also provide additional evidence of an excess of risk for exposure to asbestos.     

Occupation and larynx and hypopharynx cancer: an international case-control study in France,Italy, Spain,and Switzerland

Objective: To estimate risks for laryngeal/hypopharyngeal cancer associated with occupational titles and industrial activities. Methods: A multicentre population-based case-control study was conducted in the early 1980s in six southern European areas. Analyses included 1010 male cases and 2176 controls. Odds ratios (ORs) (adjusted for age, study area, tobacco consumption, and alcohol consumption) were estimated for 156 occupations and 70 industrial activities. Results: An excess risk has been confirmed for categories of construction workers, potters (OR: 5.91, 95% confidence intervals 1.46-24.0), butchers (2.53, 1.22–5.22), barbers (2.33, 1.00–5.40), laborers not otherwise specified (1.52, 1.12–2.06), as well as for men who had been employed in railway transport (1.52, 0.97–2.39), shipbuilding (2.05, 0.89–4.94), and hotels (2.06, 0.89–4.75). An association was also found for shoe finishers (3.23, 0.75–13.9), loggers (2.07, 0.87–4.90), and some groups of metal workers. ORs for loggers, butchers, railway transport workers, laborers, and reinforced concreters increased with duration of employment. The suggestion of a risk for machine operators among woodworkers (3.10, 0.92–10.5) conflicts with previous findings. No significant excess of risk was found for categories previously reported to be associated with laryngeal and hypopharyngeal cancer, such as drivers, mechanics, welders, machinists, and painters. Conclusions: The present study provides additional evidence to the hypothesis of a risk of cancer of the larynx/hypopharynx for workers engaged in jobs in the construction, metal, textile, ceramic, and food industries and in railway transport. Loggers were also found at risk; a previously unreported finding.     

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.     

Treatment of laryngeal cancer: the permanent challenge

There are many options to treat larynx cancers. Throughout the 20th century, surgical research has provided many partial surgery techniques (either open surgery or endoscopic CO₂ surgery). In parallel, the modification of radiotherapy schedules has notably improved the local control with definitive irradiation. The appearance of active chemotherapy regimens has also modified the concept of treatment for advanced disease, allowing a decrease in the total indications of laryngectomy, although this remains the treatment of choice in some cases. The selection of the most appropriate treatment is based on a multidisciplinary approach. Early diseases may be treated by open surgery, endoscopic laser CO₂ surgery or irradiation. Some advanced diseases may be treated by partial surgery, but the majority are theoretically candidates for radical surgery when resectable. In many instances, but not in all, chemotherapy-based larynx-preserving protocols may avoid performing such mutilating surgery. When inoperable, larynx cancers are better treated by combined chemotherapy and irradiation when the performance status of the patient is compatible with such an intensive regimen.     

Trends in the epidemiology of larynx and lung cancer in south-east England, 1985�C2004

We analysed data on 8987 larynx and 174060 lung cancer patients diagnosed between 1985 and 2004, of which 17.3% of larynx and 35.5% of lung cancers were in females. The age-standardised rates for each cancer declined in both sexes, but since the 1990s, the rates in females over 70 years of age have been diverging.     

Progress against laryngeal cancer in The Netherlands between 1989 and 2010

Cancer of the larynx is a frequently occurring head and neck cancer in The Netherlands. The main risk factors are smoking and excessive alcohol consumption. The aim of our study was to evaluate the progress against laryngeal cancer by studying trends in incidence, mortality and survival in The Netherlands. All patients in The Netherlands Cancer Registry diagnosed with invasive primary squamous cell carcinoma of the larynx during the period 1989–2010 were included for analysis. Time trends in incidence, mortality, treatment and survival were described for the total group and stratified by sex and subsite: glottis, supraglottis and subglottis. The most frequently affected subsite for men was the glottis (69%) and for women the supraglottis (55%). Glottic cancer was diagnosed at lower stages than supraglottic cancer. Incidence and mortality rates decreased for males with ?2.5 and ?2.8% per year, respectively, but remained stable for women, except for an increasing mortality rate in older women (EAPC: +2.5%). Five‐year relative survival rates were stable for glottic (85%) and supraglottic (50%) cancer, whereas patients with high‐staged cancers more often received radiotherapy. Multivariable analysis showed lower relative excess risks of dying for women, younger patients (<75 years), glottic cancer, lower stage cancer and those undergoing surgery. Changes in incidence and mortality rates are in line with changing smoking habits in The Netherlands. Declining incidence with stable survival rates gives rise to hope and worry at the same time.