Dietary intake of heterocyclic amines, meat-derived mutagenic activity, and risk of colorectal adenomas.

Meats cooked well-done by high temperature techniques produce mutagenic compounds such as heterocyclic amines (HCAs), but the amounts of these compounds vary by cooking techniques, temperature, time, and type of meat. We investigated the role of HCAs in the etiology of colorectal adenomas and the extent to which they may explain the previously observed risk for red meat and meat-cooking methods. In a case-control study of colorectal adenomas, cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy, and controls (n = 228) were found not to have colorectal adenomas at sigmoidoscopy. Using a meat-derived HCA and mutagen database and responses from a meat-cooking questionnaire module, we estimated intake of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and mutagenic activity. We calculated odds ratios and 95% confidence intervals using logistic regression adjusting for several established risk factors for colorectal adenomas or cancer. The odds ratios (95% confidence interval; P for trend test) fifth versus first quintiles are: 2.2 (1.2-4.1; P = 0.02) for DiMeIQx; 2.1 (1.0-4.3; P = 0.002) for MeIQx; 2.5(1.1-5.5; P = 0.02) for PhIP; and 3.1 (1.4-6.8; P = 0.001) for mutagenic activity. When the three HCAs were adjusted for the other two, only the trend for MeIQx (P = 0.04) remained statistically significant. When we tried to disentangle the relative contribution of the three HCAs from the meat variables, we found that MeIQx remained significantly associated with risk even when adjusted for red meat but not vice versa. When MeIQx and well-done meat were analyzed in the same model, the risks were attenuated for both. Mutagenic activity from meat remained significantly associated with increased risk even when adjusted for intake of red meat or well-done red meat, whereas the red meat and well-done red meat associations were no longer significant when adjusted for total mutagenic activity. In conclusion, we found an elevated risk of colorectal adenomas associated with high intake of certain HCAS: Further, mutagenic activity from cooked meat consumption, a measure that integrates all of the classes of mutagens, was strongly associated with risk and explained the excess risk with intake of well-done red meat.     

Meat and meat-mutagen intake and risk of non-Hodgkin lymphoma: results from a NCI-SEER case-control study

Non-Hodgkin Lymphoma (NHL) incidence has risen dramatically over past decades, but the reasons for most of this increase are not known. Meat cooked well-done using high-temperature cooking techniques produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P). This study was conducted as a population-based case-control study in Iowa, Detroit, Seattle and Los Angeles and was designed to determine whether meat, meat-cooking methods, HCAs or PAHs from meat were associated with NHL risk. This study consisted of 458 NHL cases, diagnosed between 1998 and 2000, and 383 controls. Participants completed a 117-item food frequency questionnaire (FFQ), with graphical aids to assess the meat-cooking method and doneness level, which was linked to a HCA and B[a]P database. Logistic regression, comparing the fourth to the first quartile, found no association between red meat or processed meat intake and risk for NHL [odds ratio (OR) and 95% confidence interval (CI): 1.10 (0.67-1.81) and 1.18 (0.74-1.89), respectively]. A marginally significant elevated risk for NHL was associated with broiled meat [OR and 95% CI: 1.32 (0.99-1.77); P trend = 0.09], comparing those who consumed broiled meat with those who did not. The degree to which meat was cooked was not associated with the risk for NHL, although one of the HCAs, DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), was associated with an inverse risk. Fat intake was associated with a significantly elevated risk for NHL [OR and 95% CI: 1.60 (1.05-2.45); P trend = 0.12]; in contrast, animal protein was inversely associated with risk for NHL [OR and 95% CI: 0.39 (0.22-0.70); P trend = 0.004]. Overall, our study suggests that consumption of meat, whether or not it is well-done, does not increase the risk of NHL. Furthermore, neither HCAs nor B[a]P from meat increase the risk of NHL.     

Meat, meat cooking methods and preservation, and risk for colorectal adenoma

Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo[4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma.     

Well-done, grilled red meat increases the risk of colorectal adenomas.

Red meat or meat-cooking methods such as frying and doneness level have been associated with an increased risk of colorectal and other cancers. It is unclear whether it is red meat intake or the way it is cooked that is involved in the etiology of colorectal cancer. To address this issue, we developed an extensive food frequency questionnaire module that collects information on meat-cooking techniques as well as the level of doneness for individual meat items and used it in a study of colorectal adenomas, known precursors of colorectal cancer. A case-control study of colorectal adenomas was conducted at the National Naval Medical Center (Bethesda, MD) between April 1994 and September 1996. All cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy and histologically confirmed. Controls (n = 228) were screened with sigmoidoscopy and found not to have colorectal adenomas. The subjects completed a food frequency questionnaire and answered detailed questions on meat-cooking practices. We used frequency and portion size to estimate grams of meat consumed per day for total meat as well as for meat subgroups defined by cooking methods and doneness levels. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, total caloric intake, reason for screening (routine or other), and several established risk factors for colorectal adenomas or cancer, including the use of nonsteroidal anti-inflammatory drugs, physical activity, and pack-years of cigarette smoking. There was an increased risk of 11% per 10 g/day (or 2.5 oz/week) of reported red meat consumption (OR, 1.11; CI, 1.03-1.19). The increased risk was mainly associated with well-done/very well-done red meat, with an excess risk of 29% per 10 g/day (OR, 1.29; CI, 1.08-1.54) versus an excess of 10% per 10 g/day (OR, 1.10; CI, 0.96-1.26) for consumption of rare/medium red meat. High-temperature cooking methods were also associated with increased risk; 26% per 10 g/day (OR, 1.26; CI, 1.06-1.50) of grilled red meat and 15% per 10 g/day (OR, 1.15; CI, 0.97-1.36) of pan-fried red meat consumption. There was an increased risk of colorectal adenomas associated with higher intake of red meat, most of which was due to the subgroup of red meat that was cooked until well done/very well done and/or by high-temperature cooking techniques, such as grilling. These results are consistent with the hypothesis that carcinogenic compounds formed by high-temperature cooking techniques, such as heterocyclic amines and polycyclic aromatic hydrocarbons, may contribute to the risk of developing colorectal tumors.     

Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies

The hypothesis that consumption of red and processed meat increases colorectal cancer risk is reassessed in a meta-analysis of articles published during 1973-99. The mean relative risk (RR) for the highest quantile of intake vs. the lowest was calculated and the RR per gram of intake was computed through log-linear models. Attributable fractions and preventable fractions for hypothetical reductions in red meat consumption in different geographical areas were derived using the RR log-linear estimates and prevalence of red meat consumption from FAO data and national dietary surveys. High intake of red meat, and particularly of processed meat, was associated with a moderate but significant increase in colorectal cancer risk. Average RRs and 95% confidence intervals (CI) for the highest quantile of consumption of red meat were 1.35 (CI: 1.21-1.51) and of processed meat, 1.31 (CI: 1.13-1.51). The RRs estimated by log-linear dose-response analysis were 1.24 (CI: 1.08-1.41) for an increase of 120 g/day of red meat and 1.36 (CI: 1.15-1.61) for 30 g/day of processed meat. Total meat consumption was not significantly associated with colorectal cancer risk. The risk fraction attributable to current levels of red meat intake was in the range of 10-25% in regions where red meat intake is high. If average red meat intake is reduced to 70 g/week in these regions, colorectal cancer risk would hypothetically decrease by 7-24%.     

Meat and meat-mutagen intake and pancreatic cancer risk in the NIH-AARP cohort.

Meat intake, particularly red meat, has been positively associated with pancreatic cancer in some epidemiologic studies. Detailed meat-cooking methods and related mutagens formed in meat cooked at high temperatures have not been evaluated prospectively as risk factors for this malignancy. We investigated the association between meat, meat-cooking methods, meat-mutagen intake, and exocrine pancreatic cancer in the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study cohort of 537,302 individuals, aged 50 to 71 years, with complete baseline dietary data (1995-1996) ascertained from a food frequency questionnaire. A meat-cooking module was completed by 332,913 individuals 6 months after baseline. During 5 years of follow-up, 836 incident pancreatic cancer cases (555 men, 281 women) were identified. Four hundred and fifty-nine cases had complete meat module data. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Total, red, and high-temperature cooked meat intake was positively associated with pancreatic cancer among men (fifth versus first quintile: HR, 1.41, 95% CI, 1.08-1.83, P trend = 0.001; HR, 1.42, 95% CI, 1.05-1.91, P trend = 0.01; and HR, 1.52, 95% CI, 1.12-2.06, P trend = 0.005, respectively), but not women. Men showed significant 50% increased risks for the highest tertile of grilled/barbecued and broiled meat and significant doubling of risk for the highest quintile of overall meat-mutagenic activity (P trends < 0.01). The fifth quintile of the heterocyclic amine, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline intake showed a significant 29% (P trend = 0.006) increased risk in men and women combined. These findings support the hypothesis that meat intake, particularly meat cooked at high temperatures and associated mutagens, may play a role in pancreatic cancer development.     

Meat intake, cooking-related mutagens and risk of colorectal adenoma in a sigmoidoscopy-based case-control study

Reported habits of red meat consumption, particularly red meat that has been cooked to the degree termed 'well-done', is a positive risk factor for colorectal cancer. Under high, pyrolytic temperatures, heterocyclic amines (HCA) and benzo[a]pyrene (BP) molecules can form inside and on the surface of red meat, respectively. These compounds are precursors that are metabolically converted to compounds known to act as mutagens and carcinogens in animal models, yet their role in human colorectal carcinogenesis remains to be clarified. We investigated whether intake of these compounds is associated with risk of colorectal adenoma in the context of a polyp-screening study conducted in Southern California. Using a database of individual HCAs and BP in meats of various types and subjected to specified methods and degrees of cooking, we estimated nanogram consumption of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and benzo[a]pyrene (BP). We observed a 6% increased risk of large (>1 cm) adenoma per 10 ng/day consumption of BP [OR = 1.06 (95% CI, 1.00-1.12), P (trend) = 0.04]. A major source of BP is red meat exposed to a naked flame, as occurs during the barbecuing process. Consistent with this finding an incremental increase of 10 g of barbecued red meat per day was associated with a 29% increased risk of large adenoma [OR = 1.29 (95% CI, 1.02-1.63), P (trend) = 0.04]. Individuals in the top quintile of barbecued red meat intake were at increased risk of large adenoma [OR = 1.90 (95% CI, 1.04-3.45)], compared with never consuming barbecued red meat. The consumption of oven-broiled red meat was inversely related to adenoma risk compared with non-consumers [OR = 0.49 (95% CI, 0.28-0.85)]. We did not identify any association with consumption of individual HCAs and colorectal adenoma risk. These results support the hypothesis that BP contributes to colorectal carcinogenesis.     

Meat consumption among Black and White men and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

Previous epidemiologic studies have suggested that intake of red meat may be associated with increased risk of prostate cancer. Few studies, however, have examined these associations by race. We examined intake of red meat, processed meat, and poultry in relation to incident prostate cancer among Black and White men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle in 1992 to 1993. After excluding men with a history of cancer and incomplete dietary information, 692 Black and 64,856 White men were included in the cohort. During follow-up through August 31, 2001, we documented 85 and 5,028 cases of incident prostate cancer among Black and White men, respectively. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI). No measure of meat consumption was associated with risk of prostate cancer among White men. Among Black men, total red meat intake (processed plus unprocessed red meat) was associated with higher risk of prostate cancer (RR, 2.0; 95% CI, 1.0-4.2 for highest versus lowest quartile; P(trend) = 0.05); this increase in risk was mainly due to risk associated with consumption of cooked processed meats (sausages, bacon, and hot dogs; RR, 2.7; 95% CI, 1.3-5.3 for highest versus lowest quartile; P(trend) = 0.008). This study suggests that high consumption of cooked processed meats may contribute to prostate cancer risk among Black men in the United States.     

Meat intake, preparation methods, mutagens and colorectal adenoma recurrence

Red meat intake has been shown to be associated with higher risk of colorectal cancer. Though the exact mechanisms responsible for this association remain unknown, several tumorigenic properties of meat have been proposed. One well-supported biologic mechanism is elevated exposure to the genotoxic formation of heterocyclic amines (HCAs), which occur when meat is cooked at high temperatures for a long period of time. We prospectively assessed the relation between type of meat, meat preparation method, doneness, a metric of HCAs and other mutagens and colorectal adenoma recurrence among 869 participants in a chemoprevention trial of ursodeoxycholic acid. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and associated 95% confidence intervals (CIs). Most meat variables assessed were positively but weakly associated with recurrence of any adenoma. In contrast, recurrence of advanced or multiple adenomas was more strongly associated with a number of the meat exposure variables evaluated. For recurrence of advanced lesions, significant associations were detected among individuals in the highest when compared with the lowest tertile of intake for pan-fried red meat (OR = 1.85; 95% CI = 1.10-3.13) and well/very well done red meat (OR = 1.71; 95% CI = 1.02-2.86). Significant positive associations were shown for recurrence of multiple adenomas and the following variables: processed meat (OR = 1.83; 95% CI = 1.10-3.04), pan-fried red meat (OR = 1.63; 95% CI = 1.01-2.61), well/very well done red meat (OR = 1.68; 95% CI = 1.03-2.74), 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (OR = 1.74; 95% CI = 1.07-2.82) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (OR = 1.68; 95% CI = 1.03-2.75). Our results support a meat mutagen exposure hypothesis as a potential mechanism for recurrence of clinically significant adenomatous polyps.     

Relationship of diet to risk of colorectal adenoma in men.

BACKGROUND: Rates of colorectal cancer in various countries are strongly correlated with per-capita consumption of red meat and animal fat and inversely associated with fiber consumption. There have been few studies, however, of dietary risk factors for colorectal adenomas, which are precursors of cancer. PURPOSE: Our purpose was to determine prospectively the relationship between dietary factors and risk of colorectal adenomas. METHODS: Using data from the Health Professionals Follow-up Study, we documented 170 cases of adenomas of the left colon or rectum in 7284 male health professionals who completed a food-frequency questionnaire in 1986 and who had a colonoscopy or sigmoidoscopy between 1986 and 1988. Relative risk (RR) of adenoma was determined according to quintiles of nutrient intakes. RESULTS: After adjustment for total energy intake, saturated fat was positively associated with risk of colorectal adenoma (P for trend = .006); RR for the highest versus the lowest quintile of intake was 2.0 (95% confidence interval [CI] = 1.2-3.2). Dietary fiber was inversely associated with risk of adenoma (P for trend less than .0001); RR for men in the highest versus the lowest quintile was 0.36 (95% CI = 0.22-0.60). All sources of fiber (vegetables, fruits, and grains) were associated with decreased risk of adenoma. For subjects on a high-saturated fat, low-fiber diet, the RR was 3.7 (95% CI = 1.5-8.8) compared with those on a low-saturated fat, high-fiber diet. The ratio of the intake of red meat to the intake of chicken and fish was positively associated with risk of adenoma (P for trend = .02). CONCLUSIONS: These prospective data provide evidence for the hypothesis that a diet high in saturated fat and low in fiber increases the risk of colorectal adenoma. They also support existing recommendations to substitute chicken and fish for red meat in the diet and to increase intake of vegetables, fruits, and grains to reduce risk of colorectal cancer.     

A prospective study of meat and meat mutagens and prostate cancer risk

High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of > or =7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CI, 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61). In conclusion, very well done meat was positively associated with prostate cancer risk. In addition, this study lends epidemiologic support to the animal studies, which have implicated PhIP as a prostate carcinogen.     

Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee Colorectal Polyp Study

Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy-based case-control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp-free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (p(trend) = 0.076) or red meat (p(trend) = 0.060), with an approximate 50-60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (p(trend) = 0.036 and 0.038, respectively). With a possible exception of the intake of total well-done meats (p(trend) = 0.055) or well-done red meats (p(trend) = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps.     

Processed meat intake, CYP2A6 activity and risk of colorectal adenoma

Red and processed meat intake is associated with increased risks of both colorectal adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of N-nitroso compounds (NOCs); furthermore, meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Specific NOC, HCA and PAH are mutagens and animal carcinogens. We conducted a case-control study of 146 cases of colorectal adenoma, diagnosed at sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds ratios (ORs) [and 95% confidence intervals (CIs)] and found a 2-fold increased risk in the highest, compared with the lowest, quartile of processed meat intake (95% CI = 1.0-4.0). We estimated nitrate and nitrite intake from meat using published data from the literature as well as from actual measurements of meats analyzed recently. We evaluated the interaction of processed meat and nitrate plus nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to their carcinogenic form. Results for both methods of estimating nitrate and nitrite intake were similar; compared with the lowest, the highest quartile based on measured values was associated with a 2-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) attenuated the association (OR = 1.6, 95% CI = 0.8-3.2), but other HCA and PAH had minimal effect. Higher CYP2A6 activity was not associated with risk and there was no evidence of an interaction of CYP2A6 activity with nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake from processed meat intake increases the risk of colorectal adenoma after accounting for HCA and PAH.     

Meat-related mutagen exposure, xenobiotic metabolizing gene polymorphisms and the risk of advanced colorectal adenoma and cancer

Meat mutagens, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs), may be involved in colorectal carcinogenesis depending on their activation or detoxification by phase I and II xenobiotic metabolizing enzymes (XME). Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we examined the intake of five meat mutagens and >300 single nucleotide polymorphisms (SNPs) in 18 XME genes in relation to advanced colorectal adenoma (1205 cases and 1387 controls) and colorectal cancer (370 cases and 401 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake of meat mutagens was assessed using a food frequency questionnaire with a detailed meat-cooking module. An interaction was observed between 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake and the NAT1 polymorphism rs6586714 in the adenoma study (P(interaction) = 0.001). Among individuals carrying a GG genotype, high MeIQx intake was associated with a 43% increased risk of adenoma (95% CI 1.11-1.85, P(trend) = 0.07), whereas the reverse was observed among carriers of the A variant (OR = 0.50, 95% CI 0.30-0.84, P(trend) = 0.01). In addition, we observed some suggestive (P < 0.05) modifying effects for SNPs in other XME genes (UGT1A, CYP2E1, EPHX1, AHR and GSTM3), but these were not significant after adjustment for multiple testing. This large and comprehensive study of XME genes, meat mutagens and the risk of colorectal tumours found that a NAT1 polymorphism modified the association between MeIQx intake and colorectal adenoma risk.     

Red and processed meat intake and cancer risk: Results from the prospective NutriNet‐Santé cohort study

The International Agency for Research on Cancer (WHO‐IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet‐Santé cohort (2009–2015) aged ≥35 y and who completed at least three 24 hrs dietary records during the first year of follow‐up. The risk of developing cancer was compared across sex‐specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow‐up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers [HR_Q5vs.Q1=1.31 (1.10–1.55), p_trend = 0.01) and breast cancer (HR_Q5vs.Q1 = 1.83 (1.33–2.51), p_trend = 0.002]. The latter association was observed in both premenopausal [HR_Q5vs.Q1=2.04 (1.03–4.06)] and postmenopausal women [HR_Q5vs.Q1=1.79 (1.26‐2.55)]. No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut‐offs for the 5th quintile = 46 g/d in men and 29 g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon‐rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.     

Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite and N-nitroso compounds: a follow-up study

N-nitroso compounds are potent carcinogens detected in foodstuffs. The importance of dietary nitrosamines in relation to human cancer development is, however, uncertain. We studied the relationship between intake of nitrates, nitrites and N-nitrosodimethylamine (NDMA) and risk of cancers of the gastro-intestinal tract in a cohort of 9,985 adult Finnish men and women. During a follow-up period of up to 24 years, 189 gastro-intestinal cancer cases were diagnosed in the cohort, initially free from cancer. Intake of nitrate, nitrite and NDMA were estimated, based on food-consumption data from a 1-year dietary history interview covering the total diet of the participants. A significant positive association was observed between intake of NDMA and subsequent occurrence of colorectal cancer with a relative risk (RR) between the highest and lowest quartiles of intake of 2.12 [95% confidence interval (CI) 1.04-4.33]. Of various sources of N-nitroso compounds, intake of smoked and salted fish was significantly (RR = 2.58, 95% CI 1.21-5.51) and intake of cured meat was non-significantly (RR = 1.84, 95% CI 0.98-3.47) associated with risk of colorectal cancer. No similar association was observed for intake of other fish or other meat. No significant associations were observed between NDMA intake and cancers of the head and neck combined or of the stomach or between nitrate or nitrite intake and risk of cancers of the gastro-intestinal tract. Our results are in line with the idea that N-nitroso compounds can induce colorectal cancer in humans.     

Meat consumption and colorectal cancer risk in Japan: The Takayama study

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population‐based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population‐based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.     

Meat subtypes and their association with colorectal cancer: Systematic review and meta‐analysis

Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.     

Consumption of meat,traditional and modern processed meat and colorectal cancer risk among the Moroccan population: A large-scale case–control study

The current study aimed to investigate the relationship between red and white meat subtypes, processed meat (divided into traditional “Khlii, Kaddid” and industrially processed meat) and colorectal cancer (CRC) risk, considering CRC subsites, in Moroccan adults. A case–control study was conducted including 2,906 matched case–control pairs recruited from the five largest university hospitals in Morocco. Dietary data were collected through a validated Food Frequency Questionnaire (FFQ). Multivariable odds ratios (OR) and 95% confidence intervals (CI), for the association of CRC risk with meat consumption (high vs. low intake), were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Overall, consumption of red meat was positively associated with colon cancer and CRC risk (OR = 1.23, 95% CI = 1.05–1.44; OR = 1.14, 95% CI = 1.02–1.27), respectively. In contrast, no significant association was observed between the consumption of red meat and rectal cancer risk (OR = 1.05, 95% = 0.90–1.23). Interestingly, while processed meat from industrial processes was positively associated with colon cancer, rectal cancer and CRC (OR = 1.61, 95% CI = 1.27–2.04; OR = 1.73, 95% CI = 1.34–2.23; OR = 1.67, 95% CI = 1.41–1.98), processed meat prepared using traditional methods was inversely associated with colon cancer and CRC risk (OR = 0.74, 95% CI = 0.57–0.98; OR = 0.77, 95% CI = 0.64–0.93), respectively. Furthermore, positive associations were observed between poultry intake and colon cancer risk among men (OR = 1.27, 95% CI = 1.01–1.59). Our study showed similar associations between the consumption of red meat and CRC risk in Morocco as in developed countries, while inverse associations were found for traditionally processed meat products. This is the first study to investigate the differential effects of traditional vs. westernized processed meat products in a developing country. Other studies are needed to confirm these findings and to understand the physiological pathways underlying these associations.     

Red meat, chicken, and fish consumption and risk of colorectal cancer.

BACKGROUND: Red meat and processed meat consumption have been associated with increased risk of colorectal cancer in some, but not all, relevant cohort studies. Evidence on the relationship between risk of colorectal cancer and poultry and fish consumption is inconsistent. METHODS: We conducted a prospective cohort study of 37,112 residents of Melbourne, Australia recruited from 1990 to 1994. Diet was measured with a food frequency questionnaire. We categorized the frequency of fresh red meat, processed meat, chicken, and fish consumption into approximate quartiles. Adenocarcinomas of the colon or rectum were ascertained via the Victorian Cancer Registry. RESULTS: We identified 283 colon cancers and 169 rectal cancers in an average of 9 years of follow-up. For rectal cancer, the hazard ratios [95% confidence intervals (95% CI)] in the highest quartile of consumption of fresh red meat and processed meat were 2.3 (1.2-4.2; P for trend = 0.07) and 2.0 (1.1-3.4; P for trend = 0.09), respectively. The corresponding hazard ratios (95% CIs) for colon cancer were 1.1 (0.7-1.6; P for trend = 0.9) and 1.3 (0.9-1.9; P for trend = 0.06). However, for neither type of meat was the heterogeneity between subsites significant. Chicken consumption was weakly negatively associated with colorectal cancer (hazard ratio highest quartile, 0.7; 95% CI, 0.6-1.0; P for trend = 0.03), whereas hazard ratios for fish consumption were close to unity. CONCLUSION: Consumption of fresh red meat and processed meat seemed to be associated with an increased risk of rectal cancer. Consumption of chicken and fish did not increase risk.