Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival

Jason A. Zell, Natalia Ignatenko, Hagit F. Yerushalmi, Argyrios Ziogas, David G. Besselsen, Eugene W. Gerner, Hoda Anton-Culver

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inbibitory effects in ApcMin/+ mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high-grade colon adenoma incidence in ApcMin/+ Nos2+/+ mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/sperinine N1-acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of ApcMin/+ Nos2+/+ mice (p = 0.0003). Five hundred and eleven cases from our NCl-supported CRC gene-environment study were analyzed based on self-reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1-Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10-year OS = 42% vs. 65%; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention.

Original languageEnglish (US)
Pages (from-to)459-468
Number of pages10
JournalInternational Journal of Cancer
Volume120
Issue number3
DOIs
StatePublished - Feb 1 2007

Fingerprint

Risk Reduction Behavior
Meat
Arginine
Colorectal Neoplasms
Carcinogenesis
Survival
Nitric Oxide Synthase
Celecoxib
Neoplasms
Anti-Inflammatory Agents
RNA
Ornithine Decarboxylase
Putrescine
Neoplasm Genes
Incidence
Polyamines
Knockout Mice
Pharmaceutical Preparations
Adenoma
Small Intestine

Keywords

  • Arginine
  • Celecoxib
  • Colon cancer
  • Familial colorectal cancer
  • Meat
  • Polyamines
  • Rectal cancer
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival. / Zell, Jason A.; Ignatenko, Natalia; Yerushalmi, Hagit F.; Ziogas, Argyrios; Besselsen, David G.; Gerner, Eugene W.; Anton-Culver, Hoda.

In: International Journal of Cancer, Vol. 120, No. 3, 01.02.2007, p. 459-468.

Research output: Contribution to journalArticle

Zell, Jason A. ; Ignatenko, Natalia ; Yerushalmi, Hagit F. ; Ziogas, Argyrios ; Besselsen, David G. ; Gerner, Eugene W. ; Anton-Culver, Hoda. / Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival. In: International Journal of Cancer. 2007 ; Vol. 120, No. 3. pp. 459-468.
@article{03276d660515468589d204ae6e682312,
title = "Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival",
abstract = "Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inbibitory effects in ApcMin/+ mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high-grade colon adenoma incidence in ApcMin/+ Nos2+/+ mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/sperinine N1-acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of ApcMin/+ Nos2+/+ mice (p = 0.0003). Five hundred and eleven cases from our NCl-supported CRC gene-environment study were analyzed based on self-reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1-Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10-year OS = 42{\%} vs. 65{\%}; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention.",
keywords = "Arginine, Celecoxib, Colon cancer, Familial colorectal cancer, Meat, Polyamines, Rectal cancer, Survival",
author = "Zell, {Jason A.} and Natalia Ignatenko and Yerushalmi, {Hagit F.} and Argyrios Ziogas and Besselsen, {David G.} and Gerner, {Eugene W.} and Hoda Anton-Culver",
year = "2007",
month = "2",
day = "1",
doi = "10.1002/ijc.22311",
language = "English (US)",
volume = "120",
pages = "459--468",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival

AU - Zell, Jason A.

AU - Ignatenko, Natalia

AU - Yerushalmi, Hagit F.

AU - Ziogas, Argyrios

AU - Besselsen, David G.

AU - Gerner, Eugene W.

AU - Anton-Culver, Hoda

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inbibitory effects in ApcMin/+ mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high-grade colon adenoma incidence in ApcMin/+ Nos2+/+ mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/sperinine N1-acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of ApcMin/+ Nos2+/+ mice (p = 0.0003). Five hundred and eleven cases from our NCl-supported CRC gene-environment study were analyzed based on self-reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1-Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10-year OS = 42% vs. 65%; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention.

AB - Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inbibitory effects in ApcMin/+ mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high-grade colon adenoma incidence in ApcMin/+ Nos2+/+ mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/sperinine N1-acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of ApcMin/+ Nos2+/+ mice (p = 0.0003). Five hundred and eleven cases from our NCl-supported CRC gene-environment study were analyzed based on self-reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1-Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10-year OS = 42% vs. 65%; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention.

KW - Arginine

KW - Celecoxib

KW - Colon cancer

KW - Familial colorectal cancer

KW - Meat

KW - Polyamines

KW - Rectal cancer

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=33845720127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845720127&partnerID=8YFLogxK

U2 - 10.1002/ijc.22311

DO - 10.1002/ijc.22311

M3 - Article

C2 - 17096347

AN - SCOPUS:33845720127

VL - 120

SP - 459

EP - 468

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -