Gabriel A. Kune

Case‐control study of dietary etiological factors: The Melbourne colorectal cancer study

As part of a large-scale investigation of colorectal cancer (CRC) incidence, etiology, and survival, a case-control study was conducted to identify dietary factors associated with the risk of CRC. The study compared 715 cases with 727 age- and sex-matched community controls. A quantitative diet history, assessed to be the most representative of the previous 20 years, was obtained from each subject and analyzed for both food groups and nutrients. The combination of a high-fiber and high-vegetable intake was found to be protective against large bowel cancer. Cruciferous vegetable intake was also found, although with less certainty, to be protective. Dietary vitamin C was protective for estimated intakes greater than 230 mg/day. Dietary Beta-carotene had no separate association with the risk of CRC. Beef intake was a risk factor in males but not in females. Fat intake was a risk factor for both males and females. A low intake of milk drinks was a risk for both males and females. A high intake of pork and fish was protective. The use of vitamin supplements was highly protective. A risk score, which was calculated as the number of risk factors an individual has in his or her diet, showed an increasing monotonic relationship with risk of CRC. The effects of the dietary variables were similar for colon and rectal cancer and, with the exception of beef, were similar for males and females.

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.

Alcohol consumption and the etiology of colorectal cancer: A review of the scientific evidence from 1957 to 1991

The relationship between alcohol consumption and colorectal cancer in humans has been examined in 52 major studies in the past 35 years. An association was found in five of the seven correlational studies. An elevated risk was found in about half of the 31 case-control studies and, of these, in 9 of the 10 studies using community controls but in only 5 of the 17 studies using hospital controls (p = 0.008), suggesting that the absence of association when hospital controls are used is due to a high prevalence of alcohol consumption/alcohol-related illness in the hospital controls. Of the 14 cohort studies, an association with alcohol was found in 10, while in 3 of the 4 cohort studies in which an association was not found the alcohol data obtained were somewhat restricted. A positive dose-response effect was found in two of three cohort studies and in all four case-control studies with community controls in which this effect was examined. In both case-control and cohort studies, the association was found for females and males and for colon and rectal cancer. When the type of alcohol consumed was examined separately, beer was the principal type of at-risk alcoholic beverage, with much less risk for spirits and least risk for wine. Statistically significant elevations of risk were more often found in males than in females and slightly more frequently for rectal than for colon cancer and were related almost entirely to beer, rather than to wine or spirit, consumption. The alcohol risk was independent of the dietary risk in those studies that controlled for this factor. There was some confirmatory evidence for alcohol augmentation in rodent models of chemically induced carcinogenesis in six of nine studies. The hypotheses of alcohol as a direct and specific colorectal carcinogen include increased mucosal cell proliferation, the activation of intestinal procarcinogens, and the role of unabsorbed carcinogens, particularly in beer. Also, five of six other human studies showed an association between alcohol/beer consumption and adenomatous polyps, consistent with the hypothesis that alcohol stimulates the colorectal mucosa. General or indirect carcinogenic effects of alcohol include immunodepression, activation of liver procarcinogens, and changes in bile composition, as well as nitrosamine content of alcoholic beverages and increased tissue nitrosamine levels. With alcohol/beer consumption, the overall conclusion on present evidence is that alcohol, particularly beer consumption, is an etiologic factor for colon and rectal cancer for females and males.(ABSTRACT TRUNCATED AT 400 WORDS)

Body weight and physical activity as predictors of colorectal cancer risk.

The associations between colorectal cancer and body weight (expressed as body mass index) and between colorectal cancer and physical activity were examined in 715 histologically confirmed cases of colorectal adenocarcinoma and 727 age- and sex-matched controls. The data were obtained from a large, population-based study, The Melbourne Colorectal Cancer Study, which was conducted in Melbourne, Australia. There was a statistically significant increase in the risk of rectal cancer but not of colon cancer in overweight and obese males but not in females. This association for males remained statistically significant after adjustment was made for dietary risk factors previously established for this study (Nutr Cancer 9, 21-42, 1987), with the exception of sodium intake, which produced a downward modification of the relative risk close to unity. The increased risk of rectal cancer in overweight and obese males was modified by beer intake, which was previously found to be a risk for rectal cancer in males in this study. Various levels of physical activity were not statistically significantly associated with the risk of colorectal cancer in either males or females. Also, the colorectal cancer risks associated with the body mass index were not significantly altered by adjustment for the physical activity level.

Diet, alcohol, smoking, serum β‐carotene, and vitamin A in male nonmelanocytic skin cancer patients and controls

A case-control study was conducted in Melbourne, Australia of 88 consecutive males admitted for the surgical removal of a nonmelanocytic skin cancer (histologically confirmed basal cell carcinoma and squamous cell carcinoma) and of 88 male control patients admitted for small elective surgical procedures. In both cases and controls, previous diet, alcohol consumption, and smoking habit were investigated and serum beta-carotene and vitamin A levels were measured. A statistically significant inverse relationship was found between the risk of skin cancer and a high intake of fish (p = 0.05); vegetables in general (p < 0.001); beans, lentils, or peas (p < 0.001), carrots, silverbeet (Swiss chard), or pumpkin (p < 0.001); cruciferous vegetables (cabbage, brussel sprouts, or broccoli) (p < 0.001); and beta-carotene- and vitamin C-containing foods (p = 0.004). Cases had a lower mean serum level of beta-carotene (p < 0.001) and vitamin A (p = 0.02) than controls. The incidence of skin cancer in the study was inversely related to the level of serum beta-carotene (p < 0.0001). The correlation coefficient between dietary beta-carotene/vitamin C and serum beta-carotene was 0.22 (p = 0.04). Smoking and alcohol consumption showed no statistically significant association with the risk of nonmelanocytic skin cancer. The results were similar for both cell types. A high intake of vegetables including cruciferous vegetables, beta-carotene- and vitamin C-containing foods, and fish appears to be protective for nonmelanocytic skin cancer, and this deserves further study, as does the possible etiologic relevance of the low serum levels of beta-carotene and vitamin A.

Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene

Abstract: The data reported here were obtained from the case-control arm of a large, comprehensive, population-based investigation of colorectal cancer incidence, etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in Melbourne, Australia. This part of the case-control study was designed to identify dietary factors associated with colorectal cancer risk in 715 incident cases compared with 727 age/sex frequency-matched randomly chosen community controls, in which a quantitative assessment of all foods eaten was made. New data are presented on the potential of two groups of micronutrients as protective agents, namely, those involved in DNA methylation, synthesis, and repair (folate, methionine, and vitamins B6 and B12) and those with antioxidant properties (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that for folate there was significant protection for rectal cancer in second and third quintiles of consumption but not for colon cancer, and this was similar for methionine consumption. Vitamin B6 consumption was significantly protective for both colon and rectal cancer at the higher quintiles, and this was similar for vitamin B12. Dietary selenium was significantly protective at middle quintiles of consumption at both cancer sites. Dietary vitamins E and C were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer. Lycopene was not associated with colorectal cancer risk. A combined model included vitamins E, C, and B12 and selenium as micronutrients protective for colorectal cancer and folate, which, however, showed an increased risk at the highest level of consumption. These data support the proposition that a diet containing the dietary micronutrients involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk and also that such protection can be achieved by dietary means alone.

Case-control study of alcoholic beverages as etiological factors: The Melbourne colorectal cancer study

As part of a large-scale investigation of colorectal cancer incidence, etiology, and survival, a case-control study was conducted to identify whether diet and alcohol, among other variables, were associated with the risk of colorectal cancer. This study compared 715 cases with 727 age- and sex-matched community controls. Findings from the dietary data are presented in the previous paper (Nutr Cancer 9, 21-42, 1987). The total life intake of specific alcoholic beverages was obtained from each subject. Data were classified by consumption of beer, wine, spirits, and alcohol. There was little evidence of an association of any of the alcohol variables with the risk of colon cancer. However, beer was found to be a risk factor for rectal cancer. This effect was more marked in males than in females, but the relative risks for females were consistent with those for males. Relative risk estimates changed only slightly when adjusted for the other alcohol variables and for the variables in the diet model; this suggests that the beer effect is separate from that of other alcohol variables and also from dietary variables. The age differences among beer consumers were found to be associated with cancer risk. Consumption of spirits was associated with a low risk for male rectal cancer. The risk of rectal cancer appeared to depend on beer drinking patterns in the previous 15-20 years.

Colorectal polyps, diet, alcohol, and family history of colorectal cancer: A case‐control study

A case-control study was conducted in Melbourne, Australia. Cases (n = 49) were patients who had one or more histologically confirmed adenomatous polyps larger than 1 cm in diameter previously removed by endoscopy. In both the cases and the community controls (n = 727), previous diet, alcohol consumption, and family history of colorectal cancer in near relatives were investigated. The family history rate of colorectal cancer was similar in the two groups. Those with adenomatous polyps were found to have a low fiber/vegetable intake (p = 0.04); in males, there was a high intake of beef (p = 0.04), milk drinks (p = 0.01), and beer (p = 0.05). This study provides further evidence for the hypothesis that dietary factors and alcohol consumption may play a role in the development of adenomatous colorectal polyps and that these factors are similar to dietary risk factors for colorectal cancer.

The role of chronic constipation, diarrhea, and laxative use in the etiology of large-bowel cancer: Data from the Melbourne Colorectal Cancer Study

Life-long bowel habits of 685 colorectal cancer cases and 723 age/sex frequency matched community controls were investigated as one part of a large, comprehensive, population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Self-reported chronic constipation was statistically significantly more common in cases than in controls (P=.05). Three or more bowel actions per day were reported by more cases than controls but the total number of respondents in this subset consisted of only ten cases and two controls. Otherwise, the frequency and consistency of bowel motions was similarly distributed among cases and controls. Constipation disappeared as a significant risk when simultaneously adjusted for previously determined dietary risk factors, indicating that it is the diet and not the constipation that is associated with the risk of large-bowel cancer. Additionally, a highly statistically significant association (P=.02) was found with the risk of colorectal cancer in those who reported constipation and also had a high fat intake, a finding consistent with current hypotheses of colorectal carcinogenesis. It is concluded that chronic constipation, diarrhea, and the frequency and consistency of bowel motions, as well as laxative use, are unlikely to be etiologic factors in the development of colorectal cancer. Self-reported chronic constipation is a marginally significant indicator of excess risk of large-bowel cancer and may be used as one of the indices in the screening of individuals for this cancer.

Oral and pharyngeal cancer, diet, smoking, alcohol, and serum vitamin A and β-carotene levels: A case-control study in men

A case-control study was conducted in Melbourne, Australia. Forty-one men with histologically confirmed squamous cell oral or pharyngeal cancer were compared with 398 male community controls. A statistically significant increase in risk was found for alcohol (ethanol) consumption and for smoking, and there was a synergistic effect for these two exposures. Statistically significant protection was noted with increasing intake of dietary vitamin C, dietary beta-carotene, fruit, vegetables, and dietary fiber. The mean serum levels of beta-carotene and vitamin A were statistically significantly lower when the cases were compared with another set of 88 male controls of a similar age who were hospitalized for minor surgical operations. This study confirms a causal effect of smoking and alcohol and a protective role for a high dietary intake of fruit, vegetables, cereals, and, particularly, beta-carotene- and vitamin C-containing foods.