Katarina Augustsson

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.

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 μg kg−1) or moderate (range 30–299 μg 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.

AbstractObjective: 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 α-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.

Reply: Dietary acrylamide and cancer risk: additional data on coffee

Sir, We appreciate the comments of Drs Hagmar and Tornqvist (2003) on our article assessing dietary acrylamide and cancer risk (Mucci et al, 2003). We take this opportunity to clarify some issues and to present data from additional analyses. We undertook the original investigation in light of claims by the Swedish National Food Administration that acrylamide in foods could have global impacts on cancer incidence rates. In spite of the potential limitations of the study design, our data are reassuring that acrylamide seems unlikely to be responsible for a major fraction of these cancers. As stated in our discussion, however, additional data are needed before a global assessment of any risks of dietary acrylamide can be undertaken in relation to other cancer sites and neurological diseases. The reliance on toxicological risk assessment models employed by Hagmar and Tornqvist may be questionable. Estimates of human cancer risk were extrapolated from animal models, given doses of acrylamide several fold higher than those to which humans are exposed (International Agency for Research on Cancer (IARC), 1994). We think that animal data must be generalized to humans with caution. This sentiment is reflected by IARC (2002) who considers an agent as definitely carcinogenic to humans when there is sufficient evidence from studies in humans (i.e. epidemiological evidence) and only ‘exceptionally’ in other situations. The authors present evidence from power analyses on the substantial sample size needed to detect an effect of acrylamide on human cancer risk. Notwithstanding the limitations of the risk assessment models, the authors determined an expected relative risk of 1.05 for the highest vs lowest dose. An effect estimate of this size is almost impossible to determine in any observational study. Indeed, not even a randomised clinical trial would have the power to detect this effect. The scientific methods to study such a small effect currently do not exist, and beg the question of how to best proceed to address the question of acrylamide and cancer. In addition, we must ask whether a relative risk of this size warranted the public health alarm that was generated when the findings of acrylamide in food were first announced.

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.