Can You Eat Beef Without a Pancreas
Mol Carcinog. Writer manuscript; available in PMC 2012 December vi.
Published in final edited form every bit:
PMCID: PMC3516181
NIHMSID: NIHMS421003
Pancreatic Cancer Risk: Associations with Meat-Derived Carcinogen Intake in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort
Kristin E. Anderson
anePartitioning of Epidemiology and Customs Health, University of Minnesota School of Public, Health, Minneapolis, MN
2University of Minnesota Masonic Cancer Center, Minneapolis, MN
Steven J. Mongin
2Academy of Minnesota Masonic Cancer Center, Minneapolis, MN
threeDivision of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, MN
Rashmi Sinha
4Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD
Rachael Stolzenberg-Solomon
4Epidemiology and Biostatistics Program, Segmentation of Cancer Epidemiology and Genetics, National Cancer Found, National Institutes of Health, Department of Health and Homo Services, Rockville, Doc
Myron D. Gross
2University of Minnesota Masonic Cancer Eye, Minneapolis, MN
5Laboratory Medicine and Pathology, University of Minnesota Medical Schoolhouse
Regina G. Ziegler
4Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Constitute, National Institutes of Health, Section of Health and Human being Services, Rockville, MD
Jerome Due east. Mabie
6Information Management Services, Inc., Rockville, MD
Adam Risch
6Information Direction Services, Inc., Rockville, MD
Sally Southward. Kazin
6Information Management Services, Inc., Rockville, Doctor
Timothy R. Church
2University of Minnesota Masonic Cancer Middle, Minneapolis, MN
iiiDivision of Environmental Health Sciences, University of Minnesota Schoolhouse of Public Health, Minneapolis, MN
Abstract
Background
Epidemiological studies study positive associations between high-temperature cooked meat intake and pancreatic cancer. Nosotros assessed associations betwixt dietary intake of heterocyclic amines (HCAs) and benzo(a)pyrene (BaP)—mutagens formed in meat cooked at loftier temperatures—and incident exocrine pancreatic cancer in a prospective accomplice.
Methods
The 62,581 subjects randomized to screening in the Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO) who completed an initial dietary survey that assessed meat intake, cooking methods, and doneness preferences defined the cohort. Subjects were surveyed annually for incident cancers through 2007. A National Cancer Institute research database (CHARRED) was used to estimate HCA and BaP intake and a Mutagenic Activity Index (MAI) from survey data. Proportional hazard ratios (HRs) for risk of pancreatic cancer were estimated from multivariate Cox regression models past quintile of intake, with the lowest quintile every bit the referent.
Results
During follow-upwards (median: 10 yrs), 248 cases of exocrine pancreatic cancer were confirmed. Preferences for well and very well done meat were generally associated with increased risks. Significant elevations in pancreatic cancer risk were found in upper quintiles of MAI, and of exposure to private mutagens 2-amino-iii,four,eight-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and everyman quintile of MAI, the third and fifth quintiles brought HRs of one.86 (1.22, two.85) and 1.87 two-Amino-3,8-dimethylimidazo [iv,5-f]quinoxaline (MeIQx). Compared to the (1.16, 3.02), respectively. These three exposures exhibited significant (P-trend: 0.01-0.03) positive trends in run a risk as their levels increased
Decision
Consuming well-washed meat cooked at high temperatures, which contains loftier mutagen levels, appears to confer increased chance of pancreatic cancer.
Introduction
Pancreatic cancer is rapidly fatal in most cases. Identifying and modifying risk factors tin can reduce the morbidity and bloodshed from this disease; but currently, aside from cigarette smoking and possibly elevated body mass index, few modifiable risk factors for the disease are known. Meat intake has been associated with pancreatic cancer in many epidemiologic studies, merely the information are inconsistent (Anderson 2006). This may exist due, in part, to analyses that do not account for meat preparation methods and doneness levels - in addition to intake - since these factors greatly affect the levels of carcinogens, such as heterocyclic amines (HCAs) and benzo(a)pyrene (BaP), that form in meat and fish cooked at loftier temperatures (Knize 1999).
HCAs form on the surface of meat from creatinine or creatine, amino acids and sugars (Knize 1999). Polycyclic aromatic hydrocarbons such as BaP are deposited on the meat as incomplete combustion products from burning fat that drips on the coals when meat is cooked over an open flame (Wogan 2004). Well washed barbequed or grilled meats typically contain high levels of HCAs and BaP, while baked, stewed, and microwaved meats do not contain these compounds; HCAs also form in pan-fried meats (Knize 1999; Layton 1995, Sinha 1999; Kazerouni 2001). HCAs and PAHs are known creature carcinogens and are "reasonably predictable to be human carcinogens" (Weisburger 2000; Report on Carcinogens 2004).
The NCI adult questionnaires and the CHARRED database (Sinha 2005) to guess intake of several meat carcinogens including BaP and three HCAs: 2-amino-1-methyl-six-phenylimidazo[4,v-b]pyridine (PhIP), 2-amino-3,viii-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and two-amino-iii,4,8-trimethylimidazo[iv,five-f]quinoxaline (DiMeIQx). PhIP, MeIQx and DiMeIQx are amongst the most abundant HCAs in cooked meats of nearly 20 HCAs identified (Written report on Carcinogens 2004). An additional metric derived from cooked meat samples and included in the CHARRED database relies on the total mutagenic dominance of the meat rather than on the quantity of particular carcinogens. The Mutagenic Activity Alphabetize (MAI) (revertants/grams of daily meat intake) is based on mutagenicity in the Salmonella-based Ames Assay (Ames et al, 1975).
But three epidemiologic studies, 2 case-command and ane large cohort, have collected and analyzed detailed information about cooking methods and doneness preferences, along with meat intake, in relation to pancreatic cancer (Anderson et al, 2002; 2005; Li et al, 2007; Stolzenberg-Solomon et al, 2006). In each, positive associations were reported for diverse measures of well-done meat intake; but further investigation, including boosted prospective studies, is needed earlier deeming the clan equally causal. In this report, nosotros used the CHARRED database to estimate exposures to dietary meat carcinogen and mutagenicity levels derived from questionnaires, and and so estimated the associations of these exposures with incident confirmed pancreatic cancer occurring during follow up of the PLCO cohort.
Methods
This is a prospective analysis based within the PLCO (Prostate, Lung, Colorectal, and Ovarian) multi-center cancer screening trial. From November 1993 to September 2001, that trial randomized over 150,000 subjects to each of two arms: screening and control. The baseline questionnaire of the PLCO, which was given to all subjects at the fourth dimension of randomization, provided demographic and medical history information. In improver to the baseline questionnaire, those randomized to screening were given a dietary survey around the time of their PLCO randomization. Approximately 77,500 subjects were sent the dietary survey, which provided details on meat intake, preferred cooking methods, and doneness preferences. The date of cohort entry was divers past the later of: PLCO written report randomization, baseline questionnaire completion, or dietary survey completion. The date of cohort exit corresponded to the earlier of: diagnosis with pancreatic cancer, censoring due to decease, written report dropout, or the NDI cutoff date of Dec 31, 2007.
A returned survey was considered valid for this analysis if there were no more than seven missing food frequency responses out of approximately 170 questions overall, and the subject had no personal history of pancreatic cancer. Subjects excluded on this basis contributed indirectly to principal analyses past adjustment for nonresponse (see "Statistical Methods"). The responding subjects divers the cohort for this study. Subjects or next of kin were surveyed annually for cancer incidence through 2007 and reported cancers were confirmed through medical records. Topography and histology codes from The WHO International Classification of Diseases for Oncology, 2nd Edition (ICD-O-ii) were used to ascertain cases. We included those with topographical codes C250, C251, C252, C253, C257, C258 or C259. If subjects had carcinoma in situ or particular histology codes (8150-8153, 8155, 8156, 8240-8246, 9590-9989) they were not defined equally cases and were treated as censored at the date of diagnosis. Boosted details of the design of the PLCO trial are reported in Prorok et al (2000), Gohagan et al (2000), and Hayes et al (2000).
HCA, BaP, and mutagenic activity intake
We estimated intake of HCAs, BaP and mutagenic action using responses from the food frequency questionnaire and the NCI CHARRED database (Sinha et al, 2005). Using frequency and portion size, we estimated grams of consumption of each meat item (steak, hamburger patty, pork chops, bacon, etc.) by cooking technique (fried, grilled/barbequed, oven-baked, etc.), and doneness level. Possible survey responses for doneness levels for hamburger and steak were: rare, medium rare, medium, medium well done, well done, very well washed. Those for bacon were: simply until done, well done or well-baked, charred. Some levels were aggregated to better precision; e.g., "rare to medium well" combines rare, medium rare, medium, and medium well. Then we derived intake of total HCAs and BaP by multiplying grams of meat by concentration measured for each cooking technique/doneness level contribution for that meat blazon. Similarly, the MAI was calculated by replacing "concentration of carcinogen" with "revertants per gram of meat".
The nutrient composition database used to assign HCA and BaP content values to meat items on the study questionnaire were derived from previous analyses of meat samples equally described (Sinha et al, 1998). Briefly, HCA content (PhIP, DiMeIQx, and MeIQ) and BaP were determined in meat samples cooked by various methods to different degrees of doneness by the method of Gross and Gruter (1992) using a solid-phase extraction/high-force per unit area liquid chromatography method. The MAI of sample extracts was measured using the standard plate incorporation assay with Salmonella typhimurium strain TA98 (Knize et al, 1999; Ames et al, 1975). Agents with mutagenic activity in this assay that are believed to be most relevant to cooked meat include a variety of HCAs and BaP (Layton et al, 1995; Knize et al, 1999; Report on Carcinogens 2004). The relative validity of the meat module at estimating HCA intake was investigated in 165 healthy participants. The correlation coefficients (deattentuated) were 0.lx for MeIQx and 0.36 for PhIP (Cantwell et al, 2004).
Statistical Methods
Proportional-hazards regression was used to guess the risk of pancreatic cancer every bit a function of doneness preferences and cooking methods for each of various meat groups. These models included adjustment for baseline covariates found to be significant in previous research on pancreatic cancer: age, sexual practice, cigarette smoking, instruction, race, diabetes, and total fatty intake. In the master analyses, for each of the five measures of carcinogenic exposure, quintiles were used to ascertain exposure groups. Proportional hazards regression was applied here as well, with adjustment for the same baseline covariates. For each of these derived exposures, the relative hazards among quintiles two through v was compared to the lowest quintile (referent category). Spearman's rho statistic formed the basis of a not-parametric trend test, reported equally "Spearman's P" in Results. A semi-parametric test for trend was run as well, based on a unmarried, linear term in the proportional hazards model, relating the cube root of carcinogen exposure to the relative hazard of pancreatic cancer, labeled "linear x^(1/iii)" in Results. Additional covariates were considered in split models for their impact on the primary estimates, merely as they had minimal effects, they were not retained; these included: prior history of any cancer, full energy intake, full daily fruit intake, body mass index, and recent use of alcohol, aspirin, ibuprofen and current multi-vitamin use. The proportional hazards supposition was tested for each carcinogenic exposure model. Missing responses for some survey questions, such as smoking, diabetes history and use of multi-vitamins, were treated as indicating "no" or "none" equally appropriate. To bank check for potential changes in diet driven by pre-clinical symptoms of pancreatic cancer, we varied the lag fourth dimension betwixt dietary survey completion and cohort entry by one-twelvemonth increments from zero to one, and and so two, years after the survey.
The potential for selection bias associated with nonresponse was addressed by a Horvitz-Thompson approach, using logistic regression to estimate probabilities of response as a function of baseline covariates (Horvitz and Thompson, 1952). To facilitate generalization of our results, further re-weighting by age and sex was applied to standardize the results to the U.Due south. 2000 population (U.S .Demography Bureau, 2003). All computations were washed using the statistical functions and programming language of "R" (R Development Core Team, 2010).
Results
The baseline dietary survey was sent to approximately 77,500 subjects - all those in the PLCO screening arm. Of these subjects, 62,581 (81%) returned acceptable dietary questionnaires and contribute directly to this analysis. The excluded nineteen% were primarily due to incomplete questionnaires: seven were outside of the target historic period range of 55-74 and iv had a personal history of pancreatic cancer. Selected demographic and other characteristics obtained at baseline were examined for cases and non-cases (Table i). Cohort subjects were 91% non-Hispanic Caucasian. A higher proportion of cases than noncases were male (58.1% versus 50.2%, respectively), and cases were slightly older than non-cases at study entry (65.two and 62.seven years, respectively). Consistent with well-nigh of the published epidemiologic data on this cancer, cases were more likely to report a history of diabetes, to be current or erstwhile smokers and to have fewer years of mail loftier school educational activity than non-cases. In that location were not marked differences in mean BMI betwixt cases and non-cases, nor were there marked differences in measures of dietary intake. Estimated mean dietary intake of total meat and red barbequed/grilled meat were slightly lower, while carmine meat intake was slightly higher, in cases compared to not-cases. Estimated mean dietary intake of total fatty, saturated fat, and fruit and vegetable intake were slightly lower in cases than non-cases.
Table one
Characteristic | Cases | Non-cases |
---|---|---|
Overall count (n=62,581) | 248 | 62,333 |
Historic period (y), hateful (S.D.) | 65.2 (iv.9) | 62.7 (five.three) |
Sex, count (%) | ||
Female | 104 (41.9) | 31,017 (49.eight) |
Male person | 144 (58.1) | 31, 316 (50.2) |
Race, count (%) | ||
White, non-hispanic | 220 (88.vii) | 56,549 (xc.7) |
Black, non-hispanic | x (four.0) | two,452 (iii.nine) |
Other | 18 (vii.3) | 3,312 (5.three) |
Body mass index (kg/meters2), mean (Southward.D.) | 27.1 (4.7) | 27.3 (4.9) |
Cigarette smoking status, count (%) | ||
Never smoked cigarettes | 96 (38.7) | 29, 185 (46.8) |
Electric current cigarette smoker | 42 (16.9) | 6, 223 (10.0) |
Erstwhile cigarette smoker | 110 (44.4) | 26, 905 (43.2) |
Pack-years, mean (Southward.D.) | 22.9 (31.4) | 14.7 (23.1) |
Diabetes, count (%) | ||
No | 201 (81.0) | 55, 723 (89.4) |
Yes | 38 (15.iii) | 4,562 (7.3) |
Education, count (%) | ||
Less than loftier schoolhouse | 21 (8.5) | four,249 (half dozen.viii) |
High school | 62 (25.0) | 14, 466 (23.two) |
Post-loftier school <iv Years | eighty (32.three) | 21,310 (34.2) |
Postal service-loftier school >=4 Years | 85 (34.3) | 22, 245 (35.7) |
Meat intake, mean (Due south.D.) | ||
Total meat intake (thou/twenty-four hour period) | 131.1 (124.five) | 131.6 ( 97.8) |
Total crimson meat intake (thousand/day) | 80.iv (106.0) | 78.1 (71.0) |
Total red BBQ meat intake (grand/day) | thirteen.8 (22.6) | xiv.6 (23.7) |
Dietary fat intake, mean (S.D.) | ||
Total fat intake (g/solar day) | 67.5 (43.8) | 68.1 (36.nine) |
Saturated fat intake (g/mean solar day) | 22.5 (fifteen.1) | 23.two (thirteen.5) |
Fruit and vegetable intake, hateful (S.D.) | ||
Fruit intake (servings/day) | two.vi (one.7) | 2.seven (one.9) |
Vegetable intake (servings/mean solar day) | four.1 (2.iii) | 4.2 (2.iii) |
Fruit and vegetable intake (servings/twenty-four hours) | four.i (two.3) | 4.ii (2.3) |
Person-years, unadjusted incidence rates and relative hazards of pancreatic cancer by quintiles of red meat intake, categorized by preferred level of doneness were computed (Table ii). Within the rare to medium well done preference category, increasing levels of meat intake did non show increased relative hazards. In contrast, increasing intake within the well to very well done preference category showed increasing relative hazards; the Hour for the 5th versus first quintile was 1.threescore (i.01, 2.54) and the p-value for linear trend was 0.039.
Table ii
Meat Type by Doneness Preferencesb | Number of Subjects (Per centum) N=62,581 | Person-Years of Observation | Number of Cases N=248 | Cases per 100,000 Person-Years of Observation | Relative Hazardd (95% CI) | Linear (xi/3) Trend P-Value |
---|---|---|---|---|---|---|
Red meat, rare to medium well | ||||||
Q1 | 12,383 (19.8) | 121,214 | 53 | 43.vii | one (1, 1) | |
Q2 | 12,643 (20.2) | 124,182 | 57 | 45.9 | one.xi (0.76, i.63) | |
Q3 | 12,500 (20.0) | 124,492 | 43 | 34.5 | 0.81 (0.54, 1.21) | |
Q4 | 12,538 (20.0) | 125,433 | 50 | 39.nine | 0.91 (0.61, one.34) | |
Q5 | 12,517 (20.0) | 123,565 | 45 | 36.4 | 0.84 (0.55, 1.29) | 0.364 |
Red meat, well to very well | ||||||
Q1 | 12,502 (20.0) | 126,411 | 39 | 30.nine | 1 (i, ane) | |
Q2 | 12,524 (20.0) | 125,717 | 58 | 46.1 | ane.52 (1.01, 2.29) | |
Q3 | 12,521 (xx.0) | 124,093 | 47 | 37.nine | ane.25 (0.81, 1.92) | |
Q4 | 12,517 (20.0) | 122,448 | 49 | 40.0 | ane.37 (0.88, 2.12) | |
Q5 | 12,517 (xx.0) | 120,218 | 55 | 45.8 | one.60 (1.01, 2.54) | 0.039 |
Reddish BBQ meat, rare to medium well | ||||||
cQ1-4 | 49,937 (79.8) | 494,294 | 209 | 42.3 | 1 (1, one) | |
Q5 | 12,644 (xx.two) | 124,592 | 39 | 31.3 | 0.79 (0.55, 1.13) | |
Cerise BBQ meat, well to very well | ||||||
Q1-iv | l,046 (80.0) | 498,245 | 192 | 38.five | one (1, 1) | |
Q5 | 12,535 (20.0) | 120,641 | 56 | 46.4 | 1.35 (ane.00, i.83) |
A similar design was observed for red barbequed meat. Among those who preferred rare or medium rare meat, there was no pregnant height in adventure for pancreatic cancer amid fifth quintile of intake relative to the lowest 4 quintiles. However, the same intake comparison (fifth quintile of intake relative to the everyman four quintiles) among those who prefer well or very well done red barbequed meat yielded an HR of i.35 (one.00, i.83).
A closer exam of the association of cooking methods (Tabular array 3 A) and doneness preferences (Tabular array iii B and four) with pancreatic cancer was conducted within individual meat groups. Unadjusted incidence rates as well every bit multivariate-adjusted hazard ratios were computed. There were not consistent patterns of elevated take a chance by preparation method, or within meat type by doneness preference. A proportional hazards regression model, adjusted for baseline covariates, estimated the HRs for pancreatic cancer in those preferring very well done meat compared to those reporting all other levels of doneness preferences plus those who indicated no consumption of the three specified meats (Table 4). Although the relative hazards were increased by 21% and 43% for subjects preferring very well done steak or hamburger, respectively, these were not significantly different from the null.
Table 3
(A) Meat Type past Cooking Methods | Number of Subjects (Percent) North=62,581 | Person- Years of Observation | Number of Cases N=248 | Cases per 100,000 Person- Years of Observation | Relative Hazardb (95% CI) |
---|---|---|---|---|---|
Chicken | |||||
Don't eat OR Stewed or boiled | v,732 (9.three) | 56,226 | 28 | 49.8 | 1 (1, 1) |
Roasted or baked | 36,261 (59.0) | 360,259 | 136 | 37.viii | 0.82 (0.54, one.23) |
Oven broiled | 5,415 ( 8.8) | 54,440 | 26 | 47.8 | i.02 (0.59, 1.74) |
Eat only fried chicken | 2,913 (four.7) | 28,090 | 13 | 46.iii | 0.86 (0.44, one.66) |
Grilled or barbequed | 11,117 (18.i) | 108,044 | 41 | 37.9 | 0.91 (0.56, 1.49) |
Pork chops | |||||
Don't swallow pork chops | vi,784 (11.0) | 68,699 | 19 | 27.7 | one (1, 1) |
Baked | 18,800 (xxx.4) | 187,010 | 67 | 35.8 | 1.44 (0.86, 2.40) |
Oven broiled | vi,567 (10.6) | 65,136 | 31 | 47.six | 1.78 (1.00, 3.17) |
Fried | nineteen,115 (30.9) | 187,724 | 86 | 45.8 | ane.74 (1.05, 2.ninety) |
Grilled or barbequed | 10,509 (17.0) | 102,055 | 42 | 41.2 | one.80 (one.04, 3.13) |
Hamburger | |||||
Don't eat | 3,360 (5.5) | 33,871 | 11 | 32.5 | 1 (ane, 1) |
Oven broiled | six,014 (ix.viii) | 60,300 | 23 | 38.1 | 1.11 (0.54, two.xxx) |
Pan fried | eighteen,113 (29.six) | 178,963 | 75 | 41.ix | ane.32 (0.69, 2.51) |
Grilled or barbequed | 33,638 (55.0) | 331,061 | 133 | 40.2 | one.43 (0.77, 2.67) |
Steak | |||||
Don't swallow | 4,877 (seven.nine) | 48,589 | twenty | 41.two | 1 (1, 1) |
Oven broiled | 15,385 (24.9) | 153,547 | 76 | 49.5 | i.15 (0.70, one.89) |
Pan fried | vi,611 (x.7) | 64,886 | 32 | 49.3 | 1.10 (0.62, 1.94) |
Grilled or barbequed | 34,925 (56.five) | 343,999 | 119 | 34.6 | 0.93 (0.57, one.50) |
(B) Meat Type past Doneness Preferences | Number of Subjects (Pct) N=62,581 | Person- Years of Observation | Number of Cases N=248 | Cases per 100,000 Person- Years of Observation | Relative Take a chanceb (95% CI) |
---|---|---|---|---|---|
Bacon/Sausage | |||||
Don't eat | 6,884 (11.0) | 70,255 | 25 | 35.vi | 1 (1, 1) |
Just until done | 6,050 (9.vii) | 59,133 | 28 | 47.four | ane.44 (0.83, 2.51) |
Well done or well-baked OR Charred | 49,432 (79.iii) | 487,423 | 194 | 39.eight | one.nineteen (0.78, 1.82) |
Hamburger | |||||
Don't eat | two,932 (iv.seven) | 28,900 | 10 | 34.6 | i (one, 1) |
Rare OR Medium rare | 4,300 (6.nine) | 45,590 | 26 | 57.0 | i.40 (0.67, 2.93) |
Medium | 11,836 (19.0) | 120,286 | 38 | 31.half dozen | 0.88 (0.43, one.78) |
Medium well done | 16,712 (26.viii) | 165,919 | lx | 36.two | 1.04 (0.53, 2.06) |
Well done | 23,235 (37.iii) | 223,772 | 99 | 44.2 | i.32 (0.68, 2.55) |
Very well done | 3,284 (5.3) | 31,708 | fifteen | 47.3 | ane.39 (0.62, 3.11) |
Steak | |||||
Don't swallow | iv,059 (6.five) | 39,238 | thirteen | 33.1 | 1 (1, ane) |
Rare OR Medium rare | 15,392 (24.7) | 151,366 | 72 | 47.6 | 1.43 (0.79, 2.61) |
Medium | 16,754 (26.viii) | 166,962 | 55 | 32.9 | 0.99 (0.54, 1.83) |
Medium well done | 15,808 (25.iii) | 156,905 | 61 | 38.9 | ane.16 (0.64, 2.thirteen) |
Well done | 8,345 (13.4) | 82,609 | 35 | 42.iv | 1.xix (0.62, 2.26) |
Very well done | two,079 (three.iii) | 20,317 | 12 | 59.1 | 1.68 (0.76, 3.lxx) |
Table iv
Meat Blazon and Doneness Preference | Na | Relative Hazard Estimate (95% CI)b |
---|---|---|
Bacon and sausage:Well done or crisp or charred (vs. referentc) | 62,275 | 0.99 (0.73, i.35) |
Hamburger: Very well done (vs. referent) | 62,207 | 1.21 (0.71, ii.04) |
Steak: Very well done (vs. referent) | 62,346 | 1.43 (0.lxxx, ii.56) |
For the mutagen/carcinogen exposures derived from the dietary information, DiMeIQx, MeIQx, PhIP, BaP and MAI, Spearman's correlations were calculated and ranged from 0.41 to 0.85 (Table v). Each of the 3 HCAs is a more potent mutagen than BaP and non surprisingly, is more than highly correlated with the MAI than BaP (Sugimura et al, 2000).
Table five
BaP | DiMeIQx | MeIQx | PhIP | |
---|---|---|---|---|
MAI | 0.55 | 0.79 | 0.85 | 0.eighty |
BaP | 0.41 | 0.42 | 0.61 | |
DiMeIQx | 0.74 | 0.59 | ||
MeIQx | 0.56 |
The proportional hazards regression results indicate that the MAI is associated with the nigh consistent increases in the hazard of pancreatic cancer, with elevated hazards for quintiles 2 through v existence significantly different from the nix (Figure one and Table half dozen). For both DiMeIQx and MeIQx, quintiles two and v accept significantly higher hazards than quintile 1. Furthermore, the overall upwardly tendency is significant, based on the exam for linear trend, and nearly so by the non-parametric, rank-based Spearman test of the five indicate estimates. PhIP shows upward, though not-significant, trends. BaP did not show a consequent trend of increasing intake and increasing risk. Quintiles two-four were elevated compared to quintile 1, but non significantly then and the HR for quintile 5 was shut to zippo. Tests of the proportional hazards assumption were satisfied for all five carcinogen-related measures. In sum, except for BaP, there are increased hazards associated with the higher quintiles of intake of each of these measures.
Pancreatic Cancer Gamble by Quintiles of Derived Carcinogen Exposures
For each of the 5 exposure metrics, proportional hazard estimates (dots) and 95% confidence intervals (vertical segments) for the second through the fifth quintiles, relative to the first quintile (referent category). Adjusted for non-response within PLCO, also adjusted for age, sex, race, pedagogy, diabetes, full dietary fatty intake and cigarette smoking history (pack years, and years since stopping). Likewise standardized to the U.Due south. 2000 population. "Spearman'south P" refers to the p-value based on Spearman's rho statistic equally a not-parametric examination of clan—applied hither as a test for trend. A corresponding parametric trend examination is identified by "Linear x^(1/3)", where a unmarried coefficient was added to relate the cube root of exposure to the relative hazard in the proportional hazards regression model.
Table six
Quintile of Exposurea: | Q2 | Q3 | Q4 | Q5 |
---|---|---|---|---|
MAI | one.79 (1.18, ii.70) | one.86 (ane.22, 2.85) | 1.81 (one.16, ii.83) | 1.87 (i.xvi, iii.02) |
BaP | 1.24 (0.84, 1.83) | 1.63 (1.xiii, 2.34) | 1.09 (0.72, one.64) | 0.97 (0.62, 1.52) |
DiMeIQx | i.17 (0.77, one.78) | 1.60 (1.09, 2.35) | 1.31 (0.86, 1.98) | ane.81 (1.xx, ii.74) |
MeIQx | 1.19 (0.79, 1.80) | 1.66 (1.12, two.47) | 1.34 (0.87, 2.06) | 1.75 (1.11, ii.76) |
PhIP | 0.93 (0.63, 1.37) | 1.15 (0.79, one.68) | 1.01 (0.67, 1.52) | one.xv (0.76, i.74) |
To account for possible dietary changes that could take occurred only prior to illness diagnosis, we varied the time from dietary survey completion to the defined accomplice entry from nix to one, and then two, years. This resulted in attenuation of some estimated relative hazards toward unity, but did not produce substantively unlike results from the zero-year definition. For example, the estimated relative hazards (and 95% CIs) with exposure to the fifth quintile of MAI and a one- and two-twelvemonth lag were 1.76 (1.08, ii.88) and 1.77 (1.06, ii.96), respectively. None of the other baseline covariates (described in Statistical Methods) qualitatively changed the relative hazard estimates or their precision, so they were left out of the last model.
Discussion
Associations between dietary intake of meat-borne carcinogens and pancreatic cancer were assessed in this large, multi-centre, prospective cohort study of subjects randomized to screening in the PLCO trial. The analyses propose that intake of meat-derived HCAs confers a higher risk of pancreatic cancer, merely are less suggestive for BaP. Upward trends in gamble of pancreas cancer were observed with increasing quintiles of dietary intake of DiMeIQx and MeIQx (P for linear tendency: 0.01 and 0.03, respectively). At that place were increased hazards associated with college quintiles of intake of each HCA measure and statistically significantly increased HRs were institute for the MAI. Increasing BaP intake was associated with summit in risk in some quintiles, but these were not statistically significant and there was not a dose response pattern. In that location were increased hazards among individuals reporting preferences for well-washed meat intake versus meat cooked to lower degrees of doneness, especially when both doneness preference and intake level were considered. Analyses of cooking method alone did not reveal consequent patterns of elevated risk for categories of high temperature cooked meats. It is not surprising that measures with less data about carcinogen exposure, such as meat cooking methods, doneness preferences or blazon, yield less consistent patterns of hazard than summary measures. The nigh striking and consistent patterns of increased risk with increasing intake were found with the integrated measures of HCA carcinogen intake and the MAI. These data may aid explain the inconsistent results from previous studies that analyzed limited information on meat preparation and intake.
Approximately 30 epidemiologic studies have examined meat intake in relation to pancreatic cancer and overall, and those data point to an increased risk with increasing intake of meat, only there are many inconsistencies (Anderson 2006; WCRF 2009). There have only been three studies that examined cooking methods and doneness preferences in detail and all written report increases in the hazard associated with various measures of well-washed meat intake and meat-derived carcinogens. These previous studies include a population-based case-control study in the upper Midwest (Anderson, et al., 2002; 2005); a hospital-based case-control study in Texas (Li D et al., 2007) and the NIH-AARP prospective study in retired men and women (Stolzenberg-Solomon et al., 2006).
The written report based in the upper Midwest (Anderson, et al 2005) found elevated odds ratios and 95% confidence intervals (CI) in comparisons of fifth to first quintiles of intake for PhIP 1.8 (1.0-iii.1); DiMeIQx ii.0 (1.2-iii.v), MeIQx 1.5 (0.9-2.7), BaP 2.2 (1.2-4.0) and the MAI two.four (1.3-4.3).
In the Texas study (Li D et al., 2007), daily intake of MeIQx, DiMeIQx, BaP and the MAI were all statistically significant predictors of pancreatic cancer when comparisons were based on the upper twoscore% of intake versus lower 60%. Odds ratios (95%, CI) were 1.48 (ane.12-1.95) for MeIQx; i.39(one.05-1.83) for DiMeIQx; ane.12 (0.85-1.48) for PhIP; 1.51 (1.15-1.98) for BaP and 1.41 (1.07-i.85) for the MAI.
The AARP cohort study (Stolzenberg-Solomon et al., 2006) was the simply other prospective study to have reported on meat-derived carcinogens and adventure of pancreatic cancer. The strongest associations were for meat-derived MAI in men (OR = 2.11, 95% CI one.39-3.91) for the fifth versus first quintile of intake. Loftier versus low intake of high-temperature cooked meat also increased hazard in men. The findings in women were by and large zip, which may take resulted from lower power due to a smaller number of cases too equally lower absolute intake of meat and meat-derived carcinogens.
In general, the results in the current report are like to those reported in the previous studies cited. The differences among these studies may reflect, in role, differences in methods of dietary cess of meat doneness preferences and intake. The studies in Minnesota and Texas administered questionnaires with colored photographs of meat cooked to varying degrees of doneness and in the former, three-dimensional food models were used to help subjects accurately estimate portion sizes.
The AARP study and this PLCO study relied on data from dietary surveys that assessed meat doneness preferences with written descriptions; subjects were instructed to report intake based in relation to specified serving sizes. This approach may upshot in less accurate cess of doneness preferences and intake resulting in more misclassification and attenuated HRs.
The prospective nature of this analysis inside the PLCO cohort is a force. The dietary information collected at baseline, reduces the potential for both recall bias and remember mistake present in retrospective observational studies. Another strength of this study is the utilize of multiple levels of aggregation in exposure assessment, so designed to improve gauge the total intake of the targeted carcinogens. Rather than relying on either meat doneness preferences or cooking methods lonely, both dimensions, forth with meat intake, were surveyed and incorporated. Furthermore, by using the CHARRED database of estimated mutagen content associated with these doneness preferences and cooking methods, net measures of carcinogens are obtained across the most ordinarily consumed meats. Finally, the MAI provides a measure of the total mutagenic potential across all of the meats; accounting for mutagens - both known and unknown. These aggregational features are likely responsible for the relative significance of increased MAI amid the results.
This written report does accept limitations. Despite our findings implicating meat-derived carcinogens and pancreas cancer, it is difficult to implicate specific meat-derived carcinogens and cancer risk in any population study (Written report on Carcinogens 2004). The HCAs and polycyclic aromatic hydrocarbons in cooked meat are correlated with each other and with other potentially carcinogenic constituents. Both the relative and accented amounts of these carcinogens vary in any repast or diet, and cannot be entirely captured by surveys. However, their cumulative effect as measured by the MAI, and their concentration in meats that are prepared as described merits agreement.
This was not a randomized study of these exposures and the possibility remains that these diet-related effects are confounded with some unmeasured, only more straight causal, feature. In add-on, the PLCO includes subjects that may be healthier overall, than the general population. Since healthier subjects are more than likely to accept screening, and maybe less likely to consume meat, the resulting estimates of relative take chances amongst college quintiles of exposure would then be lower than in the population at large.
In sum, the results of this prospective study back up the hypothesis that consuming meat cooked at loftier temperatures, and to a loftier caste of doneness, with the resulting product of mutagenic compounds, confers a higher risk of pancreatic cancer. This clan, if causal, identifies means to reduce risk of pancreatic cancer by reducing meat consumption or, by adopting simple changes in meat preparation techniques that reduce or eliminate production of these compounds.
Acknowledgements
The authors wish to thank the PLCO centers and staff for making this report possible. In addition, we thank Tom Hickey, IMS, for suggestions regarding this analysis. We are as well grateful to the men and women in PLCO study for their participation.
This inquiry was funded, in role, by contract number N01-CN-25513 from the U.S. National Cancer Constitute, National Institutes of Wellness, Department of Health and Homo Services and by National Institutes of Health grant DA-13333 to the University of Minnesota.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516181/
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