Intake Of Heterocyclic Amines Research Articles

Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of colorectal cancer: A hospital-based case-control study in Japan

Objective. Although associations between dietary HCA intake and colorectal cancer risk have been investigated, results have been suggestive but inconsistent. The aim of this hospital-based case-control study was to examine the impact of heterocyclic amine (HCA) intake on colorectal cancer risk. A further objective was to investigate the possible effect of genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on colorectal cancer. Material and methods. HCA exposure data were assessed using a self-administered food frequency questionnaire, and estimated HCA intake was verified by measuring the PhIP value in human hair. A total of 117 cases and 238 controls were included in these analyses. Odds ratios (ORs) were calculated using conditional logistic regression analysis to compare intake levels between the first and third tertiles. Results. No statistically significant increase in the risk of colorectal cancer with respect to total HCA intake was shown by analysis (OR = 0.99, 95% CI = 0.21–4.81). Furthermore, no association with risk was seen for individual HCAs, including PhIP, MeIQ, and MeIQx. Although variant alleles of CYP1A2 were associated with colorectal cancer (OR = 0.27; 95% CI = 0.07–0.99), genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not influence the association of HCA intake with colorectal cancer. Conclusions. In the present study in subjects with low HCA exposure and with a limited sample size, no association was found between HCA intake and colorectal cancer, or any evidence of influence by genetic polymorphisms of NAT2, CYP1A1, and CYP1A2.

Development of a quantitative food frequency questionnaire for assessing food, nutrient, and heterocyclic aromatic amines intake in Japanese Brazilians for a colorectal adenoma case–control study

Primary objective To develop of a quantitative food frequency questionnaire (QFFQ) to assess intake of specific foods, nutrients and heterocyclic aromatic amines (HAAs) in a case–control study of colorectal adenoma.Methods and procedures A cross-sectional survey conducted in a hospital in São Paulo, Brazil. A trained dietitian collected 24-h recalls from 60 Japanese Brazilian outpatients (29 men and 31 women; mean age 58 years and 57 years, respectively).Main outcomes and results Fruit, vegetable and legume intake was high, with mean daily servings consumed in men and women of 8.2 and 6.9, respectively. The QFFQ contains 161 food items presented in 15 food groupings, with particular emphasis paid to the HAA content of meat, fish and chicken items.Conclusions We have developed a QFFQ appropriate for Japanese Brazilians that will allow us to estimate HAA intake and will be used to examine our hypotheses related to foods, nutrients and HAAs, and diet–gene interactions in colorectal neoplasia in this population.

Meat Consumption, Heterocyclic Amines, NAT2, and the Risk of Breast Cancer

Meat consumption and heterocyclic amine (HCA) intake have been inconsistently associated with breast cancer risk in epidemiologic studies. Genetic variation in N-acetyltransferase2 (NAT2) has been suggested to modify the association of meat intake with breast cancer through its influence on metabolism of HCAs. We examined associations between meat intake, HCA exposure, acetylator genotype, and breast cancer risk in a case-control study of 2,686 case women and 3,508 controls. Women were asked to report their usual intake, cooking method, and preferred doneness of specific meats. We observed no association between total meat, red meat, or chicken with breast cancer risk. Women who consumed 5 or more servings of meat per week had no increased risk of breast cancer compared to women consuming fewer than 2 servings per week (OR = 0.99, 95% CI 0.84–1.15). No statistically significant associations with breast cancer were found for individual HCAs or for total estimated mutagenic activity of meat. Results varied modestly according to menopausal status. There were no statistically significant interactions with NAT2 genotype. Results do not support an important association of HCAs with breast cancer risk, although potential biases in case-control studies should be considered.

Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue

It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. A median DNA adduct level of 18.45 (interquartile range 12.81-25.65) per 10(9) nucleotides in breast tissue was observed; median HCA intake was 40.43 ng/day (interquartile range 19.55-102.33 ng/day). Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures.

Abstract B129: Xenobiotic metabolizing genes, meat intake and risk of advanced colorectal adenoma

Abstract B129 Red meat and processed meat are positively associated with risk of colorectal neoplasia. One of the potential mechanisms underlying the association of meat with cancer is via the mutagenic action of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) formed during high temperature cooking. Phase I xenobiotic metabolizing enzymes (XMEs) are involved in the initial steps of activation of xenobiotics to mutagenic and carcinogenic intermediates. Phase II XMEs convert original xenobiotic compounds and their phase I-activated metabolites to polar and detoxified metabolites. However, with certain compounds, such as HCAs, phase II XMEs may further activate metabolites to form other carcinogenic species. We evaluated 29 single nucleotide polymorphisms (SNPs) in several phase I (CYP1A1, CYP1B1, CYP2A6, CYP2C9, CYP2E1, and CYP3A4) and phase II (EPHX1, GSTM1, GSTM2, GSTT1, NAT1, NAT2, NQO1, SULT1A1, and SULT1A2) XME genes in relation to advanced colorectal adenoma and investigated potential effect modification by red meat, HCA, and PAH intake. All SNPS were selected based on known or suggested functional relevance and a minor allele frequency of 5% or greater in Caucasians. Participants were selected from individuals who were enrolled in the screening arm (n = 77,483) of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial between 1993 and 1999. We compared 720 cases with advanced colorectal adenoma (size of 1cm or greater, high grade dysplasia, or villous components, including tubulovillous) of the distal colon or rectum to 746 controls frequency matched on gender and ethnicity (negative for left-sided polyp by sigmoidoscopy). Using a 137-item food frequency questionnaire that included detailed questions on meat cooking methods and doneness levels in conjunction with a HCA and PAH database, we generated intake estimates of the HCAs, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), and the PAH, benzo[a]pyrene (B[a]P) in ng/day. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age, gender, and ethnicity. Tests for interaction were based on the likelihood ratio test by comparing models with and without interaction terms. Overall, we found weak or null associations between the individual XME genes or SNPs with risk of advanced colorectal adenoma. However, we observed interactions between intake of PhIP and variation in CYP1B1 (rs10012 Pinteraction = 0.019; rs1056836 Pinteraction = 0.019), and NQO1 (rs1800566 Pinteraction = 0.007) with advanced colorectal adenoma. We also found evidence of interaction with intake of B[a]P for variation in CYP1B1 (rs10012 Pinteraction = 0.005) and CYP3A4 (rs2242480 Pinteraction = 0.02). In addition, there was an interaction with intake of red meat and CYP1B1 (rs10012 Pinteraction = 0.013) and NAT1 variants (rs15561 Pinteraction = 0.037). However, when considering multiple comparisons, these interactions did not fall below a false discovery rate threshold of 0.20. Our results are intriguing and suggest that common variants in XME genes may modify the association of red meat, HCA, and PAH intake with advanced colorectal adenoma, but require confirmation in larger studies. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B129.

Abstract B134: Meat, meat cooking methods, meat mutagens and heme iron as risk factors for lung cancer in the NIH-AARP Diet and Health Study

Abstract B134 Background Lung cancer is the leading cause of cancer death worldwide. Red and processed meat consumption may have a role in lung cancer pathogenesis due to their fat content and the carcinogens produced during high temperature cooking and preservation, as well as endogenous formation of mutagens from heme. However, no prospective study has examined meat intake by cooking method or doneness level. We investigated whether meat type, cooking method, doneness level, and intake of specific meat mutagens and heme iron, were associated with lung carcinoma. Methods In 278,192 men and 189,560 women, aged 50-71 yrs, from the NIH-AARP Diet and Health study, meat intake was assessed using a 124-item food frequency questionnaire and an additional meat-cooking module. Dietary data were used in conjunction with the CHARRED-database to estimate intake of individual heterocyclic amines (HCAs), benzo[a]pyrene and heme iron. We carefully controlled for lifelong smoking history using a 9-level smoking variable. Results During up to 8 years of follow-up, 4,089 men and 2,272 women were diagnosed with incident lung carcinoma. Men in the highest compared to the lowest quintile of red and processed meat intake had statistically significant higher risk of lung carcinoma (red meat: HRQ5vs.Q1=1.22, 95%CI=1.09-1.38); processed meat: HRQ5vs.Q1=1.24, 95%CI=1.11-1.38) in a multivariable model. In women, there was a borderline statistically significant increase in risk for red (HRQ5vs.Q1=1.13, 95%CI=0.97-1.31), but not for processed meat (HRQ5vs.Q1=1.00, 95%CI=0.87-1.16). In men only, the risk of lung carcinoma was associated with well/very-well done meat (HRT3vs.T1=1.20, 95%CI=1.07-1.35) and the heterocyclic amine MeIQx (HRQ5vs.Q1=1.20, 95%CI=1.05-1.39). Heme iron from meat increased the risk of lung carcinoma in both men (HRQ5vs.Q1=1.25, 95%CI=1.07-1.45) and women (HRQ5vs.Q1=1.18; 95%CI=0.99-1.42). Conclusion Consumption of a diet high in red meat was associated with lung carcinoma risk in both men and women, and a high intake of processed meat was associated with risk in men only. High temperature cooking and associated mutagens, and heme iron in meat may explain the role of meat in lung carcinogenesis. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B134.

Meat Intake, Heterocyclic Amine Exposure, and Metabolizing Enzyme Polymorphisms in Relation to Colorectal Polyp Risk

Most colorectal cancers arise from adenomatous polyps or certain hyperplastic polyps. Only a few studies have investigated potential genetic modifiers of the associations between meat intake and polyp risk, and results are inconsistent. Using data from the Tennessee Colorectal Polyp Study, a large colonoscopy-based study, including 1,002 polyp cases (557 adenoma only, 250 hyperplastic polyp only, 195 both polyps) and 1,493 polyp-free patients, we evaluated the association of colorectal polyp risk with carcinogen exposure from meat and genetic polymorphisms in enzymes involved in heterocyclic amine (HCA) metabolism, including N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2), cytochrome P450 1A2 (CYP1A2), and aryl hydrocarbon receptor (AhR). Data on intake levels of meats by preparation methods, doneness preferences, and other lifestyle factors were obtained. Fourteen single nucleotide polymorphisms in the AhR, CYP1A2, NAT1, and NAT2 genes were evaluated. No clear association was found for any polymorphisms with polyp risk. However, apparent interactions were found for intake of meat and HCAs with AhR, NAT1, and NAT2 genotypes, and the interactions were statistically significant for the group with both adenomatous and hyperplastic polyps. Dose-response relationships with meat or HCA intake were found only among those with the AhR GA/AA (rs2066853) genotype, NAT1 rapid, or NAT2 rapid/intermediate acetylators but not among those with other genotypes of these genes. This dose-response relationship was more evident among those with both AhR GA/AA and the NAT1 rapid acetylator than those without this genotype combination. These results provide strong evidence for a modifying effect of metabolizing genes on the association of meat intake and HCA exposure with colorectal polyp risk.

Metabolism and toxicology of heterocyclic aromatic amines when consumed in diet: Influence of the genetic susceptibility to develop human cancer. A review

There is not sufficient scientific evidence to support the hypothesis that human cancer risk is specifically due to the intake of heterocyclic aromatic amines (HAAs) in diet. Epidemiological evidence appears to imply two main factors in the HAAs carcinogenicity. These factors are the very high frequency of consumption of red meats, and very darkly browned meats from cooking, which are HAAs-containing foods. The present review focuses on the fact that the cancer risk is notably enhanced when certain genotypes related to HAAs metabolism are present. Thus, genetic predisposition seems to be the main factor in cancer development related to HAAs, and possibly the co-presence of other mutagenic compounds in diet.

Intake of heterocyclic aromatic amines from meat in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort

It was the aim of the present study to estimate the intake of heterocyclic aromatic amines (HCA) from meat, which have been associated with cancer risk in several epidemiological studies, of 21 462 subjects who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg. This was accomplished by using a detailed dietary questionnaire that assessed meat consumption, cooking methods, and degree of browning of the respective food items. Median total HCA intake from meat was 31 ng/d (mean 69 ng/d), which was lower than results observed in previous studies. 2-Amino-1-methyl-6-phenylimidazo[4,5b]pyridine was the most common HCA in this cohort (median 17; mean 48 ng/d). The present study offers the opportunity of a detailed examination of the associations between meat cooking as well as HCA intake from meat and cancer risk in a prospective way.

Modification by N-acetyltransferase 1 genotype on the association between dietary heterocyclic amines and colon cancer in a multiethnic study

Objective Colorectal cancer incidence is greater among African Americans, compared to whites in the U.S., and may be due in part to differences in diet, genetic variation at metabolic loci, and/or the joint effect of diet and genetic susceptibility. We examined whether our previously reported associations between meat-derived heterocyclic amine (HCA) intake and colon cancer were modified by N-acetyltransferase 1 (NAT1) or 2 (NAT2) genotypes and whether there were differences by race. Methods In a population-based, case-control study of colon cancer, exposure to HCAs was assessed using a food-frequency questionnaire with a meat-cooking and doneness module, among African Americans (217 cases and 315 controls) and whites (290 cases and 534 controls). Results There was no association with NAT1*10 versus NAT1-non*10 genotypes for colon cancer. Among whites, there was a positive association for NAT2-“rapid/intermediate” genotype [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.0, 1.8], compared to the NAT2-“slow” that was not observed among African Americans. Colon cancer associations with HCA intake were modified by NAT1, but not NAT2, regardless of race. However, the “at-risk” NAT1 genotype differed by race. For example, among African Americans, the positive association with 2-amino-1-methyl-6-phenyl-imidazo[4,5- b]pyridine (PhIP) was confined to those with NAT1*10 genotype (OR = 1.8; 95% CI = 1.0, 3.3; P for interaction = 0.02, comparing highest to lowest intake), but among whites, an association with 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) was confined to those with NAT1-non*10 genotype (OR = 1.9; 95% CI = 1.1, 3.1; P for interaction = 0.03). Conclusions Our data indicate modification by NAT1 for HCA and colon cancer associations, regardless of race. Although the at-risk NAT1 genotype differs by race, the magnitude of the individual HCA-related associations in both race groups are similar. Therefore, our data do not support the hypothesis that NAT1 by HCA interactions contribute to differences in colorectal cancer incidence between African Americans and whites.

Development of a Meat Frequency Questionnaire for Use in Diet and Cancer Studies

Objective To develop a meat frequency questionnaire to assess dietary heterocyclic amine intake. The meat frequency questionnaire is designed to obtain information on meat types, cooking methods, and doneness preferences that predict heterocyclic amine concentrations in different meats. Design Total and specific meat intakes were determined by a standard food frequency questionnaire (FFQ) and compared with that determined by the meat frequency questionnaire. Subjects/setting Three-hundred fourteen African-American males participating in a clinic-based study of prostate disease and heterocyclic amine intake were administered the two questionnaires in a cancer education center prior to undergoing screening evaluations for prostate disease. Main outcome measures Fried, broiled, and grilled vs total meat intake was assessed using the meat frequency questionnaire vs FFQ, respectively. Specific meat items included in the meat frequency questionnaire were evaluated as factors potentially explaining discrepancies in meat intake estimated using the two questionnaires. Seasonal variation in meat intake was also examined. Statistical analysis Correlation coefficients for intake of total meat and individual meat groups determined by FFQ vs meat frequency questionnaire were calculated. Seasonal differences in meat and estimated heterocyclic amine intakes were evaluated by t test, adjusted for multiple comparisons. Results Meat intakes determined by the two questionnaires were well-correlated (Pearson r=0.69); however, total meat assessed by the meat frequency questionnaire exceeded total meat assessed by the FFQ in 30% of participants. Total energy and intake of heterocyclic amine−associated meat were greatest when the meat frequency questionnaire was administered during winter months. Conclusions The heterocyclic amine meat frequency questionnaire provided a fractional measure of total meat intake and identified specific heterocyclic amine-containing meat items underreported in a standard FFQ.

Food, nutrient and heterocyclic amine intake and the risk of bladder cancer

Fruit and vegetable intake has been linked to bladder cancer risk; however, evidence for other foods or specific dietary factors is inconclusive. The association between diet and bladder cancer risk was evaluated among 912 incident bladder cancer cases and 873 controls in Spain. Data were consistent with a reduced bladder cancer risk associated with high fruit intake; however, the association was significant only among current smokers (OR (95% CI) for 5th versus 1st quintile: 0.5 (0.3–0.9), p trend = 0.009). Evaluation of food subgroups showed significant inverse associations with high intakes of berries, Liliaceae vegetables and yellow-orange vegetables. The latter association was stronger among individuals with the GSTM1 present than the null genotype (0.4 (0.2, 0.7) and 0.9 (0.6, 1.3), respectively; p for interaction = 0.04). Meat or fish intake, their cooking methods or level of doneness, or heterocyclic amine intakes were not significantly associated with risk. Intake of folate, other B-vitamins (B12, B6, B2) and retinol was also associated with a reduced risk, the strongest associations being for vitamin B6 (0.6 (0.4, 0.8) p trend = 0.0006) and retinol (0.6 (0.4–0.9) p trend = 0.004). Our findings indicate that fruit and vegetable intake, as well as B-vitamin and retinol intake might be associated with a reduced bladder cancer risk.

Dietary intake of heterocyclic amines in relation to socio-economic, lifestyle and other dietary factors: estimates in a Swedish population

To estimate the dietary intakes of heterocyclic amines (HCAs), to examine the intakes in relation to socio-economics, lifestyle and other dietary factors and to compare the classification of subjects by intake of HCA versus intake of meat and fish. Cross-sectional analysis within the Malmö Diet and Cancer (MDC) cohort. Data were obtained from a modified diet history, a structured questionnaire on socio-economics and lifestyle, anthropometric measurements and chemical analysis of HCAs. HCA intake was cross-classified against meat and fish intake. The likelihood of being a high consumer of HCAs was estimated by logistic regression analysis. Dietary intakes were examined across quintiles of HCA intake using analysis of variance. Baseline examinations conducted in 1991-1994 in Malmö, Sweden. A sub-sample of 8599 women and 6575 men of the MDC cohort. The mean daily HCA intake was 583 ng for women and 821 ng for men. Subjects were ranked differently with respect to HCA intake compared with intake of fried and baked meat and fish (kappa = 0.13). High HCA intake was significantly associated with lower age, overweight, sedentary lifestyle and smoking. Intakes of dietary fibre, fruits and fermented milk products were negatively associated with HCA intake, while intakes of selenium, vegetables, potatoes, alcohol (among men) and non-milk-based margarines (among women) were positively associated with HCA intake. The estimated daily HCA intake of 690 ng is similar to values obtained elsewhere. The present study suggests that lifestyle factors (e.g. smoking, physical activity, fruit and vegetable intakes, and types of milk products and margarines) may confound associations between HCA intake and disease. The poor correlation between HCA intake and intakes of fried meat and fish facilitates an isolation of the health effects of HCAs.

Cooked Meat and Risk of Breast Cancer—Lifetime Versus Recent Dietary Intake

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.

Validity of a self-administered food frequency questionnaire in the assessment of heterocyclic amine intake using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) levels in hair

Several case-control studies have reported possible associations between heterocyclic amine (HCA) intake and the risk of cancer. The validity of questionnaires used to assess HCA intake has hardly been examined, however; in particular, no biomarker able to serve as an independent measure of habitual HCA intake has been established. In this study, we examined the validity of HCA intake estimated from a food frequency questionnaire (FFQ) using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in hair as a reference method. Study subjects were 20 volunteers (7 men and 13 women) aged 25–57 years residing in Tokyo or neighboring cities in Japan. The subjects completed the FFQ, and gave 3–5 g of hair twice at an interval of 1–3 months for use in establishing validity. Results showed that intakes of PhIP, MeIQ, Trp-P-1, and total HCA by the FFQ were significantly correlated with PhIP levels in hair when adjustment was made for melanin content ( r = 0.47, r = 0.50, r = 0.55, and r = 0.51, respectively). The present study indicates that HCA intake estimated from this FFQ provides a reasonable ranking of individuals to allow the analysis of associations between HCA intake and risk of cancer in large-scale epidemiological studies.

Improved Exposure Assessment for Heterocyclic Amine Intake

TS6-05 Abstract: Exposure assessment methods were developed to link responses to detailed questions about meat preparation and doneness preference to a database of heterocyclic amine (HCA) concentrations in cooked meats prepared in controlled cooking studies to estimate intake of total and individual HCAs. Similar methods applied in previous case–control studies using less detailed data on meat intake and cooking methods have shown how such information on cooking techniques and dietary preferences can improve assessment of associations between HCA intakes and several types of cancer. A previous assessment of U.S. national dietary intakes showed that black men consume twice the level of HCAs previously estimated for white men in the United States due to use of more frequent cooking by methods that form HCAs and to greater consumption of meats with high HCA levels (primarily grilled chicken). Using the more detailed survey approach, results from a prospective, clinic-based study indicate that the black men in Oakland, California, show HCA intakes consistent with the national pattern. Preliminary results from this study also indicate a significant positive association between estimated HCA intake among the black men studied and highly elevated prostate serum antigen (PSA) levels (PSA ≥20 ng/mL) associated with substantial likelihood of developing prostate cancer. Potential exposure misclassification may arise using these new survey methods due to cultural differences in cooking practices and subjective terminology used to describe cooked foods. Data from this study and a study of HCAs in home-cooked meat samples will be presented to demonstrate improved methods for HCA exposure assessment.

2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) level in human hair as biomarkers for dietary grilled/stir-fried meat and fish intake

Several case-control studies have reported possible associations between heterocyclic amine (HCA) intake and the risk of cancer. However, the validity of a questionnaire to assess HCA intake has hardly been examined. In particular, no biomarker which could serve as an independent measure of habitual HCA intake has been established. Therefore, the validity of a questionnaire to assess HCA intake by means of a biomarker remains to be investigated. In this study, we examined the availability of hair HCAs as a biochemical indicator of dietary intake of HCAs. Study subjects were 20 volunteers (7 men and 13 women) aged 25–57 years, either residents of Tokyo or the neighboring cities in Japan. We collected individual weighed dietary records (DR) over 28 consecutive days. Approximately 3–5 g of hair was collected twice from all subjects before and after DR at intervals of 1–3 months. The mean (S.D.) 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) level of hair was 1376.0 pg/g hair (928.9) and 16.6 ng/g melanin (12.3). A steady increase in the mean PhIP level in hair from the lowest to the highest tertile of the grilled/stir-fried meat intake was observed ( P = 0.009), but not in the grilled/stir-fried fish intake ( P = 0.461). The PhIP level in hair was highly correlated with the grilled/stir-fried meat intake ( r = 0.68) but not with the grilled/stir-fried fish intake ( r = 0.28). These observations were made of hair with and without melanin adjustment. The present study indicates that the PhIP level in hair can be used as a biological indicator of dietary intake of HCAs.

Dietary Intake of Heterocyclic Amines and Benzo(a)Pyrene: Associations with Pancreatic Cancer

Heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons, formed in temperature- and time-dependent manners during the cooking of meat, are mutagens and carcinogens. We sought to assess the association between dietary intake of HCA and benzo(a)pyrene [B(a)P] and exocrine pancreatic cancer in a population-based case-control study. Subjects (193 cases and 674 controls) provided information on their usual meat intake and preparation method, e.g., stewed, fried, or grilled/barbecued, etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness. We used a meat-derived HCA, B(a)P, and mutagen database with a questionnaire to estimate intake of PhIP, DiMeIQx, MeIQx, B(a)P, and mutagenic activity (revertants/g of daily meat intake). Data were analyzed with unconditional logistic regression. In analyses adjusted for age, sex, smoking, education, race, and diabetes, the odds ratio and 95% confidence interval for the highest compared with the lowest quintile were as follows: PhIP, 1.8 (1.0-3.1); DiMeIQx, 2.0 (1.2-3.5); MeIQx, 1.5 (0.9-2.7); B(a)P, 2.2 (1.2-4.0); and mutagenic activity, 2.4 (1.3-4.3). HCAs and B(a)P from well-done barbecued and pan-fried meats may be associated with increased risk for pancreatic cancer.

Development of a food frequency questionnaire module and databases for compounds in cooked and processed meats

There is ample evidence from basic research and animal carcinogenicity studies that heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are mutagens and carcinogens. However, there was a paucity of human data due to a lack of appropriate investigative tools. We developed the first validated cooked meat module within a food frequency questionnaire (FFQ) in the United States of America and created databases to be used in conjunction with this FFQ to estimate intake of HCAs and benzo[a]pyrene, a marker of PAHs. It became clear that other aspects of meat may also contribute to carcinogenesis; in particular, we are pursuing two additional areas: processed meat and iron exposure in relation to cancer risk. To investigate these hypotheses, we have expanded the cooked meat module to include detailed information on processed meats and fish. In addition, we are developing two databases, one for total iron and heme iron in cooked meat and the other for nitrite, nitrate, and N-nitroso compounds in processed meats. In this report, we will outline the methods used to develop the meat questionnaires, the databases, a software package for generating the intake values, and the methods used to generate nutritional data from nationally representative samples.

Heterocyclic amines and genotype of N-acetyltransferases as risk factors for prostate cancer

A variety of carcinogenic heterocyclic amines are produced during the cooking of meat at high temperatures. These carcinogens are metabolized by N-acetyltransferases (NAT), which are polymorphic in the population. This study examined associations between prostate cancer (PCa) and the consumption of different kinds of meat, heterocyclic amine intake and NAT genotypes. PCa patients and controls were recruited in the Syracuse, NY area. Levels of meat and heterocyclic amine intakes were determined from validated surveys and NAT genotypes were determined by the sequences of PCR-amplified DNA from buccal swabs. A total of 152 cases and 161 controls were eligible for analysis. There was an association between PCa and history of PCa in the first-degree blood relatives (OR = 4.59, 95% CI 2.21-9.70), and family history of bladder cancer (P < 0.02). However, there was no association with the history of other cancers. There was no association between PCa and either 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) intake, or NAT1 and NAT2 genotypes. However, there was a trend of association with MeIQx and with rapid NAT2 and NAT1*10 in combination with PhIP. A new NAT1 allele with a frequency of one out of 544 chromosomes was found in the Caucasian subjects.