No excess risk of colorectal cancer among alcoholics followed for up to 25 years.

We conducted a population-based retrospective cohort study among 179,398 Swedish patients hospitalised for alcoholism from 1970 to 1994, and found no excess risk for colorectal cancers, overall or at any anatomical subsite. Our findings challenge the hypothesis that alcohol intake is a risk factor for cancer of the large bowel.

Investigation of interaction between N-acetyltransferase 2 and heterocyclic amines as potential risk factors for colorectal cancer.

Fast N-acetyltransferase 2 (NAT2) acetylators may be at increased risk of colorectal cancer through the activation of carcinogenic heterocyclic amines (HA), which are produced by meat cooked at high temperatures and are found in cigarette smoke. A study of 500 incident colorectal cancer cases and population controls, matched for age, sex and general practitioner, was conducted in the UK to investigate this hypothesis. Usual meat intake and lifetime smoking habits were estimated using a detailed questionnaire administered by interview. Subjects also indicated how well cooked they ate their meat. Subjects were classified as fast or slow NAT2 acetylators on the basis of NAT2 genotype. Complete genotype data were available on 433 matched pairs. The risk of colorectal cancer showed a steady increase with meat intake, rising to an odds ratio of 1.51 [95% confidence interval (1.03, 2.23)] for the highest versus the lowest quartile, after adjustment for total energy intake, and this was even more pronounced for red meat [odds ratio 1.97 (1.30, 2.98)]. However, this effect was not influenced by the preference for well-done meat. Smoking was also associated with an increased risk [odds ratio 1.47 (1.10, 1.98) for ever- versus never-smokers]. In both cases and controls approximately 40% of subjects were classified as fast acetylators, and the risks associated with (red) meat intake and smoking did not vary with NAT2 status. This study provides no support for the hypothesis that fast NAT2 acetylators are at increased risk of colorectal cancer, even if exposed to high levels of HA from well-cooked meat or smoking.

Dietary acrylamide and cancer of the large bowel, kidney, and bladder: absence of an association in a population-based study in Sweden.

Recently, disturbingly high levels of acrylamide were unexpectedly detected in widely consumed food items, notably French fries, potato crisps, and bread. Much international public concern arose since acrylamide has been classified as a probable carcinogen, although based chiefly on laboratory evidence; informative human data are largely lacking. We reanalysed a population-based Swedish case-control study encompassing cases with cancer of the large bowel (N=591), bladder (N=263) and kidney (N=133), and 538 healthy controls, assessing dietary acrylamide by linking extensive food frequency data with acrylamide levels in certain food items recorded by the Swedish National Food Administration. Unconditional logistic regression was used to estimate odds ratios, adjusting for potential confounders. We found consistently a lack of an excess risk, or any convincing trend, of cancer of the bowel, bladder, or kidney in high consumers of 14 different food items with a high (range 300-1200 microg kg(-1)) or moderate (range 30-299 microg kg(-1)) acrylamide content. Likewise, when we analysed quartiles of known dietary acrylamide intake, no association was found with cancer of the bladder or kidney. Unexpectedly, an inverse trend was found for large bowel cancer (P for trend 0.01) with a 40% reduced risk in the highest compared to lowest quartile. We found reassuring evidence that dietary exposure to acrylamide in amounts typically ingested by Swedish adults in certain foods has no measurable impact on risk of three major types of cancer. It should be noted, however, that relation of risk to the acrylamide content of all foods could not be studied.

A prospective study on intake of animal products and risk of prostate cancer.

OBJECTIVE: Association between animal products and prostate cancer have been observed in numerous observational studies, but it is not clear whether the high fat content of these foods or some other component accounts for these associations. We examine these associations among 51,529 men who contributed detailed dietary data. METHODS: Participants of the Health Professionals Follow-Up Study completed a semiquantitative food-frequency questionnaire in 1986, and subsequently in 1990 and 1994. Other data on potential risk factors were collected at baseline and in subsequent questionnaires during follow-up. Between 1986 and 1996, 1897 total cases of prostate cancer (excluding stage A1) and 249 metastatic cancers were identified. We used pooled logistic regression for analyses of diet and prostate cancer. RESULTS: Intakes of total meat, red meat, and dairy products were not associated with risk of total or advanced prostate cancer. An elevated risk for metastatic prostate cancer was observed with intake of red meat (relative risk (RR)= 1.6 for top vs. bottom quintile comparison, 95% confidence interval (CI) = 1.0-2.5); this association was slightly attenuated after controlling for saturated and alpha-linolenic fatty acids (RR = 1.5, 95% CI = 0.88-2.5). Processed meats, bacon and beef, pork or lamb as a main dish each contributed to an elevated risk of metastatic prostate cancer. Dairy product intake increased risk of metastatic prostate cancer (RR = 1.4, 95% CI = 0.91-2.2 for top vs. bottom quintile comparison), but no association remained after controlling for calcium and other fatty acids. A high intake in both red meat and dairy product was associated with a statistically significant two-fold elevation in risk of metastatic prostate cancer, compared to low intake of both products; however, most of the excess risk could be explained by known nutritional components of these foods. CONCLUSIONS: Intakes of red meat and dairy products appear to be related to increased risk of metastatic prostate cancer. While known nutrients, such as calcium and fatty acids, may explain most of the dairy association observed, it appears that a portion of the risk of metastatic prostate cancer associated with red meat intake remains unexplained.

Deflection of the local interstellar dust flow by solar radiation pressure.

Interstellar dust grains intercepted by the dust detectors on the Ulysses and Galileo spacecrafts at heliocentric distances from 2 to 4 astronomical units show a deficit of grains with masses from 1 x 10(-17) to 3 x 10(-16) kilograms relative to grains intercepted outside 4 astronomical units. To divert grains out of the 2- to 4-astronomical unit region, the solar radiation pressure must be 1.4 to 1.8 times the force of solar gravity. These figures are consistent with the optical properties of spherical or elongated grains that consist of astronomical silicates or organic refractory material. Pure graphite grains with diameters of 0.2 to 0.4 micrometer experience a solar radiation pressure force as much as twice the force of solar gravity.

A population-based dietary inventory of cooked meat and assessment of the daily intake of food mutagens.

Frequent consumption of meat has been associated with an increased risk of colorectal cancer. Such a risk may be due to naturally occurring compounds in the meat, substances added to the meat, or agents formed during cooking. Concerning the latter alternative, mutagenic heterocyclic amines are multi-site animal carcinogens, but their relevance to human cancer has yet to be determined. In the present study, we made a population-based inventory of cooked meat dishes consumed in the county of Stockholm, ranked dishes according to cooking method and frequency of consumption and, in addition, determined levels of mutagenic activity in six commonly consumed fried meat dishes. Meat was consumed, on average, 493 times per year, giving 1.4 daily servings. Frying was the most common way to cook meat. When ranking meat dishes according to intake frequency, the top eight dishes were as follows: sausage, steak casserole, meatballs, pork chops, pork belly, bacon, ground beef patties, and finally, mince-meat sauce. The frying sessions were performed under controlled conditions at four different temperatures, and we documented the degree of surface browning and measured mutagenic activity in six frequently eaten dishes (sausage, meatballs, pork chops, pork belly, ground beef patties, and minute beef). We found extracts from all six dishes to be mutagenic, and a mean daily dose of exposure was calculated, giving 862 revertants. This investigation leaves no doubt that a major portion of the total meat consumption is fried before ingestion and that fried meat dishes frequently consumed by an elderly population in Stockholm contain mutagenic substances. Furthermore, the study provides usable information for future epidemiological research in which it is necessary to disentangle the effect of meat per se from the effect of potentially carcinogenic heterocyclic amines.

Assessing the human intake of heterocyclic amines: limited loss of information using reduced sets of questions.

The aim of this study was to evaluate loss of information from a reduced food frequency questionnaire as compared with an extensive reference method developed to assess the intake of heterocyclic amines (HCAs). Food frequency data were linked to concentrations of HCAs in cooked foods to estimate the individual daily exposure to a combination of five HCAs. The number of food items in the questionnaire was reduced and selected in three ways: (a) according to the contribution to the estimated total intake; (b) the between-person variance; or (c) dishes included in other studies. The effect on sensitivity, specificity, concordance, the correlation coefficient, kappa, and simulated relative risks was determined using information from a population-based study conducted in Stockholm. Only a limited amount of misclassification was introduced when the number of dishes was reduced from 39 to 15 or 20, and no major difference was seen when dishes were selected according to the total intake or the between-person variance. Our data indicate that for a specific exposure, such as HCAs, the loss of accuracy in an analytical epidemiological study is small and may not be relevant when the number of dishes in a food frequency questionnaire is decreased, if the initially chosen dishes are carefully selected and cover a reasonable part of the total intake or between-person variance.

Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study.

BACKGROUND: Heterocyclic amines formed in cooked meat and fish are carcinogenic in animal models and form DNA adducts in human beings. We undertook a study to assess whether these substances are related to the risks of cancer in the large bowel and urinary tract. METHODS: In a population-based case-control study, cases were identified from the Swedish cancer registry. Controls were randomly selected from the population register. Information on intake of various foods and nutrients was assessed by questionnaire, with photographs of foods cooked at various temperatures. We measured the content of heterocyclic amines in foods cooked under these conditions. FINDINGS: Information was retrieved from 553 controls, 352 cases of colon cancer, 249 cases of rectal cancer, 273 cases of bladder cancer, and 138 cases of kidney cancer. The response rate was 80% for controls and 70% for cases. The estimated daily median intake of heterocyclic amines was 77 ng for controls, and 66 ng, 63 ng, 96 ng, and 84 ng for cases with cancer of the colon, rectum, bladder, and kidney, respectively. The relative risk for the intake of heterocyclic amines (highest vs lowest quintile) was 0.6 (95% CI 0.4-1.0) for colon cancer, 0.7 (0.4-1.1) for rectal cancer, 1.2 (0.7-2.1) for bladder cancer, and 1.0 (0.5-1.9) for kidney cancer. Seven cases, but no controls, had an estimated daily intake of heterocyclic amines above 1900 ng. INTERPRETATION: Intake of heterocyclic amines, within the usual dietary range in this study population, is unlikely to increase the incidence of cancer in the colon, rectum, bladder, or kidney. For daily intakes above 1900 ng, our data are consistent with human carcinogenicity, but the precision was extremely low.

Assessment of the human exposure to heterocyclic amines.

Heterocyclic amines are possible human carcinogens and fried meat is an important source of exposure in the Western diet. To study the effect of heterocyclic amines in humans, accurate assessment of individual food consumption is essential. Parameters influencing the intake include the amount and type of meat ingested, frequency of consumption, cooking method, cooking temperature and the duration of cooking. The aim of the present study was to develop a practical method for assessing individual intakes of specific heterocyclic amines in a large sample of people. This has been done by combining information on food consumption and laboratory findings of heterocyclic amines in food products. Diet was assessed using a semi-quantitative food frequency questionnaire including photos of fried meat and, in all, 22 dishes were cooked and chemically analyzed. The method was employed in an elderly population in Stockholm to estimate the daily mean intake of the five heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The total daily intake ranged from none to 1816 ng, with a mean intake of 160 ng, which is well below estimates reported previously. Highest amounts ingested were of PhIP (mean 72, range 0-865 ng/day) and MeIQx (mean 72, range 0-1388 ng/day), followed by DiMeIQx (mean 16, range 0-171 ng/day), while MeIQ and IQ were ingested only in very small amounts (mean <1 ng/day).

Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues.

Fourteen cooked dishes with their corresponding pan residues were analysed for polar and non-polar heterocyclic amines using HPLC. The choice of foods, including beef, pork, poultry, game, fish, egg and sausages, was based on an investigation of an elderly population in Stockholm participating in an analytical epidemiological case-control study on cancer risks after intake of heterocyclic amines. The food items were prepared using normal household cooking practices, and to reflect the wide range of surface browning of the cooked dishes that would be encountered in this population, four cooking temperatures were used in the range 150-225 degrees C. For all food samples, the total amount of heterocyclic amines formed at 150 degrees C was less than 1 ng/g cooked product, and at 175 degrees C less than 2 ng/g. The highest concentrations of heterocyclic amines were detected in fillet of pork, reindeer meat and chicken breast fried at 200 and 225 degrees C and their corresponding pan residues. The total sum of 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine was about 1 microgram per 100 g portion (including pan residues) for reindeer meat and chicken breast, and between 1.9 and 6.3 micrograms per 100-g portion for fillet of pork. PhIP was the most abundant heterocyclic amine, identified in 73 of 84 samples, and the highest concentration of PhIP, 32.0 ng/g, was found in the pan residue from fillet of pork cooked at 225 degrees C. The non-polar heterocyclic amines 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole were detected in the range of 0.5-7.4 ng/g in most foods cooked at 225 degrees C, and also in meat sauce prepared at 200 and 175 degrees C. The other heterocyclic amines tested for: 2-amino-3-methylimidazo-[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-6-methyl-pyrido-[1,2-a:3',2'-d]-imidazole and 2-aminodipyrido-[1,2-a:3',2'-d]imidazole, were present only at very low or non-detectable levels. The low recoveries of the amino-alpha-carbolines 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-9H-pyrido[2,3-b]indole made it impossible to quantify them. However, the co-mutagenic substances 1-methyl-9H-pyrido-[3,4-b]indole and 9H-pyrido[3,4-b]indole were detected at levels of about 1-30 ng/g in most of the dishes cooked at 200 and 225 degrees C.

Supplementary iron intake and risk of cancer: reversed causality?

Dietary iron intake and body iron stores have been suggested to increase cancer risk, especially colorectal cancer. Within a population-based case-control study in Stockholm county 1993-94, information on dietary and supplementary iron intake were collected through a food frequency questionnaire. An initially noted positive association between intake of supplementary iron and colorectal cancer risk was reversed when intake 5 years prior to cancer diagnosis was subtracted. Reversed causality due to early disease giving symptoms of iron shortage, resulting in iron supplementation, is an issue to consider when a possible association between intake of iron and cancer risk is investigated.

Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues.

Frequent consumers of meat have an increased risk of colorectal cancer and possibly also of breast, stomach, pancreas and urinary bladder cancer. Bacon, 'Falusausage', ground beef, meatballs, pork belly, pork chops and sliced beef account for more than one-third of the intake of fried meat of the population of Stockholm of age 50-75. These dishes were fried at four temperatures (150, 175, 200 and 225 degrees C) representing normal household cooking practices in Stockholm. Heterocyclic amines in these dishes were analysed using solid-phase extraction and HPLC. The heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were recovered. The formation of IQ was favoured by moderate cooking temperatures; IQ was detected in one meat sample cooked at 150 degrees C and in some pan residues. The yield of MeIQx, DiMeIQx and PhIP increased with the temperature. For several of the meat dishes, the content of heterocyclic amines in the pan residue was as large or larger than for corresponding piece of meat. The highest levels of MeIQx were 23.7 ng/g in the meat and 23.3 ng/g in the pan residue. Corresponding data for DiMeIQx were 2.7 and 4.1 ng/g and for PhIP 12.7 and 82.4 ng/g. The study leaves little doubt that mutagenic heterocyclic amines are ingested by the population of Stockholm, and added to previous epidemiological studies from the same area, the combined data are consistent with human carcinogenicity of heterocyclic amines. However, analytical epidemiological studies are needed before any statement on causality can be made.