Rashmi Sinha

Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study.

Animal studies have shown that dietary intake of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), causes increased levels of tumors at several sites, particularly in the upper gastrointestinal tract. However, the role of dietary intake of BaP and cancer in humans is not clear. We created a BaP database of selected food products that could be linked to Food Frequency Questionnaires (FFQs) to estimate BaP intake. BaP levels were measured for each food line-item (composite samples) which consisted of a variety of foods in a FFQ. Composite sample parts were derived from the Second National Health and Nutrition Examination Survey (NHANES II) which represents the most common food items consumed by the general population. Meat samples were cooked by different techniques in controlled conditions, and by various restaurants and fast-food chains. Non-meat products were purchased from the major national supermarket chains. The quantities of BaP were measured using a thin-layer chromatography (TLC)/spectrofluorometer technique and were highly correlated with both BaP (r=0.99) [corrected] and sum of carcinogenic PAH (r=0.98) measured by HPLC technique. We linked our database to the results from a FFQ and estimated the daily BaP intake of various food items in 228 subjects in the Washington, DC metropolitan area. The highest levels of BaP (up to about 4 ng BaP/g of cooked meat) were found in grilled/barbecued very well done steaks and hamburgers and in grilled/barbecued well done chicken with skin. BaP concentrations were lower in meats that were grilled/barbecued to medium done and in all broiled or pan-fried meat samples regardless of doneness level. The BaP levels in non-meat items were generally low. However, certain cereals and greens (e.g. kale, collard greens) had levels up to 0.5 ng/g. In our population, the bread/cereal/grain, and grilled/barbecued meat, respectively, contributed 29 and 21 percent to the mean daily intake of BaP. This database may be helpful in initial attempts to assess dietary BaP exposures in studies of cancer etiology.

Meat Intake and Mortality: A Prospective Study of Over Half a Million People

BACKGROUND High intakes of red or processed meat may increase the risk of mortality. Our objective was to determine the relations of red, white, and processed meat intakes to risk for total and cause-specific mortality. METHODS The study population included the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study cohort of half a million people aged 50 to 71 years at baseline. Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of meat intake. The covariates included in the models were age, education, marital status, family history of cancer (yes/no) (cancer mortality only), race, body mass index, 31-level smoking history, physical activity, energy intake, alcohol intake, vitamin supplement use, fruit consumption, vegetable consumption, and menopausal hormone therapy among women. Main outcome measures included total mortality and deaths due to cancer, cardiovascular disease, injuries and sudden deaths, and all other causes. RESULTS There were 47 976 male deaths and 23 276 female deaths during 10 years of follow-up. Men and women in the highest vs lowest quintile of red (HR, 1.31 [95% CI, 1.27-1.35], and HR, 1.36 [95% CI, 1.30-1.43], respectively) and processed meat (HR, 1.16 [95% CI, 1.12-1.20], and HR, 1.25 [95% CI, 1.20-1.31], respectively) intakes had elevated risks for overall mortality. Regarding cause-specific mortality, men and women had elevated risks for cancer mortality for red (HR, 1.22 [95% CI, 1.16-1.29], and HR, 1.20 [95% CI, 1.12-1.30], respectively) and processed meat (HR, 1.12 [95% CI, 1.06-1.19], and HR, 1.11 [95% CI 1.04-1.19], respectively) intakes. Furthermore, cardiovascular disease risk was elevated for men and women in the highest quintile of red (HR, 1.27 [95% CI, 1.20-1.35], and HR, 1.50 [95% CI, 1.37-1.65], respectively) and processed meat (HR, 1.09 [95% CI, 1.03-1.15], and HR, 1.38 [95% CI, 1.26-1.51], respectively) intakes. When comparing the highest with the lowest quintile of white meat intake, there was an inverse association for total mortality and cancer mortality, as well as all other deaths for both men and women. CONCLUSION Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality.

Association of Coffee Drinking with Total and Cause-Specific Mortality

BACKGROUND Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. METHODS We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. RESULTS During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. CONCLUSIONS In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.).

A Prospective Study of Red and Processed Meat Intake in Relation to Cancer Risk

Background Red meat and processed meat have been associated with carcinogenesis at several anatomic sites, but no prospective study has examined meat intake in relation to a range of malignancies. We investigated whether red or processed meat intake increases cancer risk at a variety of sites. Methods and Findings The National Institutes of Health (NIH)-AARP (formerly the American Association for Retired Persons) Diet and Health Study is a cohort of approximately 500,000 people aged 50–71 y at baseline (1995–1996). Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals within quintiles of red and processed meat intake. During up to 8.2 y of follow-up, 53,396 incident cancers were ascertained. Statistically significant elevated risks (ranging from 20% to 60%) were evident for esophageal, colorectal, liver, and lung cancer, comparing individuals in the highest with those in the lowest quintile of red meat intake. Furthermore, individuals in the highest quintile of processed meat intake had a 20% elevated risk for colorectal and a 16% elevated risk for lung cancer. Conclusions Both red and processed meat intakes were positively associated with cancers of the colorectum and lung; furthermore, red meat intake was associated with an elevated risk for cancers of the esophagus and liver.

Human Gut Microbiome and Risk for Colorectal Cancer

We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.

A Large Prospective Study of Meat Consumption and Colorectal Cancer Risk: An Investigation of Potential Mechanisms Underlying this Association

Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P(trend) < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P(trend) = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P(trend) = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P(trend) = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P(trend) < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P(trend) <0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations.

Trends in meat consumption in the USA

OBJECTIVE To characterize the trends, distribution, potential determinants and public health implications of meat consumption within the USA. DESIGN We examined temporal trends in meat consumption using food availability data from the FAO and US Department of Agriculture (USDA), and further evaluated the meat intake by type (red, white, processed) in the National Health and Nutrition Examination Surveys (NHANES) linked to the MyPyramid Equivalents Database (MPED). RESULTS Overall meat consumption has continued to rise in the USA and the rest of the developed world. Despite a shift towards higher poultry consumption, red meat still represents the largest proportion of meat consumed in the USA (58 %). Twenty-two per cent of the meat consumed in the USA is processed. According to the NHANES 2003-2004, total meat intake averaged 128 g/d. The type and quantities of meat reported varied by education, race, age and gender. CONCLUSIONS Given the plausible epidemiological evidence for red and processed meat intake in cancer and chronic disease risk, understanding the trends and determinants of meat consumption in the USA, where meat is consumed at more than three times the global average, should be particularly pertinent to researchers and other public health professionals aiming to reduce the global burden of chronic disease.

A Prospective Study of Serum C-Reactive Protein and Colorectal Cancer Risk in Men

Chronic inflammation has been implicated in the etiology of colorectal cancer. C-reactive protein (CRP), a sensitive marker of inflammation, has been investigated with regard to colorectal cancer in only three previous studies, and the results from these investigations were inconsistent. We examined serum CRP levels in relation to colorectal cancer incidence in a nested case-control study within the Alpha Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 Finnish males enrolled from 1985 to 1988 with follow-up through April 2002. Colorectal cancer cases were ascertained by the Finnish Cancer Registry; this analysis included 130 cases of colorectal cancer (with available blood), which occurred between 1990 and April 30, 2002, and 260 matched controls. Baseline median CRP levels were approximately 25% higher among colorectal cancer cases (3.4 mg/L) than controls (2.6 mg/L; P = 0.04). Relative to men in the lowest quartile of CRP concentration, men in the highest quartile had an odds ratio of 2.9 (95% confidence interval, 1.4-6.0) for developing colorectal cancer with a dose-response relationship supported (P(trend) = 0.006). The relation between CRP and incident colorectal cancer was modified by body mass index such that the association was stronger among lean individuals than in heavier individuals (P(interaction) = 0.018). These results support the notion that chronic low-grade inflammation is a marker for increased risk of colorectal cancer.

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.

An epidemiologic approach to studying heterocyclic amines

Diets containing substantial amounts of red meat may increase the risk of colorectal, pancreatic, breast, prostate, and renal cancer. The association with red meat intake may be due to a combination of factors, such as content of fat, protein, and iron, and/or meat preparation (e.g. cooking or preserving methods). Laboratory results have shown that meats cooked at high temperatures contain heterocyclic amines (HCAs) known to be mutagenic and carcinogenic in animals. Many older epidemiologic studies of colon cancer using surrogates for HCA exposure from meat (for example, doneness level, surface browning, frying, intake of gravy) have produced suggestive but inconsistent results. These discrepancies may have resulted in part from having used dietary questionnaires that combined meat-cooking practices in ways that made the intake of HCAs difficult to estimate. Thus, over the last decade we have taken a multidisciplinary approach to investigating whether the association with red meat intake can be explained by meat-cooking practices that produce mutagens/carcinogens. To estimate intake, a database for HCAs have been developed and used in conjunction with a validated meat-cooking food frequency questionnaire (FFQ). To develop biological markers of internal exposure, a metabolic study was conducted where subjects consumed controlled amounts of meat cooked at low and high temperatures. The role of meat type, cooking methods, doneness levels, and meat-cooking mutagens were examined in case-control studies of colorectal adenomas, lung, and breast cancers using both questionnaire information and biomarkers. In a case-control study of colorectal adenomas, an increased risk was associated with a high intake of red meat. Most of this risk was due to intake of red meat cooked until well/very well done and/or by high-temperature cooking techniques such as grilling. Linking the FFQ information to HCA database, the impact several HCAs on risk was evaluated. An increased risk was associated with higher intake of MeIQx, possibly PhIP. Red meat, especially fried and/or well-done red meat, was associated with increased risk of lung cancer in a population-based case-control study. In addition, an increase in risk was demonstrated among non-smokers and moderate smokers for MeIQx intake. In a case-control study of breast cancer well-done red meat and PhIP was associated with increased risk of breast cancer. In this manuscript I will provide one approach to studying the relation of meat cooking-mutagens and cancer risk and will suggest the types of studies that may be required in the future to clarify these associations.