Grant Details
Grant Number: |
5R01CA055751-05 Interpret this number |
Primary Investigator: |
Lang, Nicholas |
Organization: |
University Of Arkansas Med Scis Ltl Rock |
Project Title: |
Acetylation and N-Oxidation in Colorectal Cancer |
Fiscal Year: |
1998 |
Abstract
A case-control study to examine the independent and combined efforts of
arylamine acetylator status and N-oxidation status and heterocyclic and
aromatic amine exposure on the risk of development of colorectal cancer
is proposed.
The specific aims of this grant application are:
To confirm the initial findings of our pilot study regarding the roles
of heterocyclic and aromatic amine metabolism and exposure as putative
risk factors from the diet or the environment. The sources amine
metabolism and exposure as putative risk factors from the diet or the
environment. The sources of heterocyclic and aromatic amines to be
studied are cigarette smoking, diet and cooking methods; the metabolic
pathways to be studied include heterocyclic amine N-oxidation status and
O-acetylation status.
The experimental design involves the conduct of arylamine
acetyltransferase and arylamine N-oxidation phenotyping on patients with
a history of carcinoma of the colorectum and on control patients. This
phenotyping will be performed using a single dose of caffeine
administered as an instant coffee drink and will involve the collection
of a single urine specimen. The caffeine metabolites will be measured
by HPLC and the phenotype determined by the radio of AFMU/1X for
acetylation and [17U+17X]/137X for N-oxidation.
The source of exposure will be determined by the use of the Willett Food
Frequency Questionnaire which will provide estimates of total energy
intake and micronutrients. Additional information regarding specific
exposure to amines will be gathered in a personal interview that covers
smoking history, dietary practices (e.g., char-broiled, roasted or
microwaved meat), occupational history, medical and family history and
basic demographic information.
We hypothesize that heterocyclic and aromatic amines are colon
carcinogens for humans. These compounds occur primarily in cooked fish
and meat and are also present in cigarette smoke. Based on results from
our pilot study, we hypothesize that the group at greatest susceptibility
for the development of colorectal cancer will be those people who are
both rapid acetylation and rapid N-oxidation phenotypes, who are exposed
to high levels of arylamines, for example, red mead cooked well done.
This study should provide information on relevant individual risk of
factors that could serve as a basis for attempts to modify high risk
behavior (e.g., environmental exposure and dietary practices) among those
at greatest risk to develop cancer. It is a unique opportunity for
collaboration between laboratory scientist and traditional
epidemiologists in developing a new approach to cancer risk
identification.
Publications
The Urinary Metabolite Profile Of The Dietary Carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Is Predictive Of Colon Dna Adducts After A Low-dose Exposure In Humans
Authors: Malfatti M.A.
, Dingley K.H.
, Nowell-Kadlubar S.
, Ubick E.A.
, Mulakken N.
, Nelson D.
, Lang N.P.
, Felton J.S.
, Turteltaub K.W.
.
Source: Cancer Research, 2006-11-01 00:00:00.0; 66(21), p. 10541-7.
PMID: 17079477
Related Citations
Cyp3a43 Pro(340)ala Polymorphism And Prostate Cancer Risk In African Americans And Caucasians
Authors: Stone A.
, Ratnasinghe L.D.
, Emerson G.L.
, Modali R.
, Lehman T.
, Runnells G.
, Carroll A.
, Carter W.
, Barnhart S.
, Rasheed A.A.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2005 May; 14(5), p. 1257-61.
PMID: 15894682
Related Citations
Association Of Sult1a1 Phenotype And Genotype With Prostate Cancer Risk In African-americans And Caucasians
Authors: Nowell S.
, Ratnasinghe D.L.
, Ambrosone C.B.
, Williams S.
, Teague-Ross T.
, Trimble L.
, Runnels G.
, Carrol A.
, Green B.
, Stone A.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2004 Feb; 13(2), p. 270-6.
PMID: 14973106
Related Citations
Novel Markers Of Susceptibility To Carcinogens In Diet: Associations With Colorectal Cancer
Authors: Sweeney C.
, Coles B.F.
, Nowell S.
, Lang N.P.
, Kadlubar F.F.
.
Source: Toxicology, 2002-12-27 00:00:00.0; 181-182, p. 83-7.
PMID: 12505289
Related Citations
Analysis Of Total Meat Intake And Exposure To Individual Heterocyclic Amines In A Case-control Study Of Colorectal Cancer: Contribution Of Metabolic Variation To Risk
Authors: Nowell S.
, Coles B.
, Sinha R.
, MacLeod S.
, Luke Ratnasinghe D.
, Stotts C.
, Kadlubar F.F.
, Ambrosone C.B.
, Lang N.P.
.
Source: Mutation Research, 2002-09-30 00:00:00.0; 506-507, p. 175-85.
PMID: 12351157
Related Citations
Cyp2a6 Activity Determined By Caffeine Phenotyping: Association With Colorectal Cancer Risk
Authors: Nowell S.
, Sweeney C.
, Hammons G.
, Kadlubar F.F.
, Lang N.P.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2002 Apr; 11(4), p. 377-83.
PMID: 11927498
Related Citations
The Role Of Human Glutathione S-transferases (hgsts) In The Detoxification Of The Food-derived Carcinogen Metabolite N-acetoxy-phip, And The Effect Of A Polymorphism In Hgsta1 On Colorectal Cancer Risk
Authors: Coles B.
, Nowell S.A.
, MacLeod S.L.
, Sweeney C.
, Lang N.P.
, Kadlubar F.F.
.
Source: Mutation Research, 2001-10-01 00:00:00.0; 482(1-2), p. 3-10.
PMID: 11535243
Related Citations
Validity Of An Elisa For N-acetyltransferase-2 (nat2) Phenotyping
Authors: Wong P.
, Banerjee K.
, Massengill J.
, Nowell S.
, Lang N.
, Leyland-Jones B.
.
Source: Journal Of Immunological Methods, 2001-05-01 00:00:00.0; 251(1-2), p. 1-9.
PMID: 11292476
Related Citations
An Allele-specific Polymerase Chain Reaction Method For The Determination Of The D85y Polymorphism In The Human Udp-glucuronosyltransferase 2b15 Gene In A Case-control Study Of Prostate Cancer
Authors: MacLeod S.L.
, Nowell S.
, Plaxco J.
, Lang N.P.
.
Source: Annals Of Surgical Oncology, 2000 Dec; 7(10), p. 777-82.
PMID: 11129427
Related Citations
Relationship Of Phenol Sulfotransferase Activity (sult1a1) Genotype To Sulfotransferase Phenotype In Platelet Cytosol
Authors: Nowell S.
, Ambrosone C.B.
, Ozawa S.
, MacLeod S.L.
, Mrackova G.
, Williams S.
, Plaxco J.
, Kadlubar F.F.
, Lang N.P.
.
Source: Pharmacogenetics, 2000 Dec; 10(9), p. 789-97.
PMID: 11191883
Related Citations
In Vivo Human Metabolism Of [2-14c]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (phip)
Authors: Lang N.P.
, Nowell S.
, Malfatti M.A.
, Kulp K.S.
, Knize M.G.
, Davis C.
, Massengill J.
, Williams S.
, MacLeod S.
, Dingley K.H.
, et al.
.
Source: Cancer Letters, 1999-09-01 00:00:00.0; 143(2), p. 135-8.
PMID: 10503892
Related Citations
Glucuronidation Of 2-hydroxyamino-1-methyl-6-phenylimidazo[4, 5-b]pyridine By Human Microsomal Udp-glucuronosyltransferases: Identification Of Specific Ugt1a Family Isoforms Involved
Authors: Nowell S.A.
, Massengill J.S.
, Williams S.
, Radominska-Pandya A.
, Tephly T.R.
, Cheng Z.
, Strassburg C.P.
, Tukey R.H.
, MacLeod S.L.
, Lang N.P.
, et al.
.
Source: Carcinogenesis, 1999 Jun; 20(6), p. 1107-14.
PMID: 10357796
Related Citations
Dna And Protein Adduct Formation In The Colon And Blood Of Humans After Exposure To A Dietary-relevant Dose Of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Authors: Dingley K.H.
, Curtis K.D.
, Nowell S.
, Felton J.S.
, Lang N.P.
, Turteltaub K.W.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 1999 Jun; 8(6), p. 507-12.
PMID: 10385140
Related Citations
The Identification Of [2-(14)c]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Metabolites In Humans
Authors: Malfatti M.A.
, Kulp K.S.
, Knize M.G.
, Davis C.
, Massengill J.P.
, Williams S.
, Nowell S.
, MacLeod S.
, Dingley K.H.
, Turteltaub K.W.
, et al.
.
Source: Carcinogenesis, 1999 Apr; 20(4), p. 705-13.
PMID: 10223203
Related Citations
Human Cytochrome P4501a2
Authors: Landi M.T.
, Sinha R.
, Lang N.P.
, Kadlubar F.F.
.
Source: Iarc Scientific Publications, 1999; (148), p. 173-95.
PMID: 10493258
Related Citations
Identification Of Enzymes Responsible For The Metabolism Of Heme In Human Platelets
Authors: Nowell S.A.
, Leakey J.E.
, Warren J.F.
, Lang N.P.
, Frame L.T.
.
Source: The Journal Of Biological Chemistry, 1998-12-11 00:00:00.0; 273(50), p. 33342-6.
PMID: 9837908
Related Citations
Thomas G. Orr Memorial Lectureship. Colon Cancer From Etiology To Prevention
Authors: Lang N.P.
.
Source: American Journal Of Surgery, 1997 Dec; 174(6), p. 578-82.
PMID: 9409576
Related Citations
Polymorphisms Of Cyp1a1 And Gstm1 Influence The In Vivo Function Of Cyp1a2
Authors: MacLeod S.
, Sinha R.
, Kadlubar F.F.
, Lang N.P.
.
Source: Mutation Research, 1997-05-12 00:00:00.0; 376(1-2), p. 135-42.
PMID: 9202749
Related Citations