TY - JOUR
T1 - Human sensitivity to PhIP
T2 - A novel marker for prostate cancer risk
AU - El-Zein, Randa
AU - Etzel, Carol J.
AU - Lopez, Mirtha S.
AU - Gu, Yun
AU - Spitz, Margaret R.
AU - Strom, Sara S.
N1 - Funding Information:
This work was supported in part by National Cancer Institute grants CA90270, CA84964, CA88304, CA98549, NIEHS ES07784 and the M. D. Anderson Prostate Cancer Research Program.
PY - 2006/10/10
Y1 - 2006/10/10
N2 - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been implicated in the development of colon, prostate and mammary gland tumors in rats. In this study, we developed a modified in vitro mutagen sensitivity assay, with activated PhIP (N-OH-PhIP) as the challenge mutagen and chromosome aberrations as the endpoint, and applied it in a pilot prostate cancer case-control study of 81 cases and 84 age and ethnicity-matched controls. Our results showed significantly higher baseline breaks among the cases, mean ± S.E. = 1.86 ± 0.23 versus 0.96 ± 0.14 in controls; P = 0.006. Individuals with high baseline breaks (dichotomized at the control median) had a 36% increased risk for PC (OR = 1.36; 95% CI = 1.08-1.72). In stratified analysis, high baseline breaks was associated in younger participants (≤60 years) with an OR of 1.71 (1.14-2.57) and in those with a positive family history of PC, an OR of 1.43 (0.97-2.11). PhIP treatment induced significantly higher breaks in cases, mean ± S.E. = 5.07 ± 0.39 versus 3.83 ± 0.24 in controls; P = 0.05. Higher PhIP-induced breaks was associated with an overall 17% increased risk for PC (OR = 1.17; 95% CI = 1.03-1.33), a significantly increased risks (OR = 1.19; 95% CI = 1.00-1.41) among younger participants, non-smokers (OR = 1.39, 1.03-1.88) and 1.20 (1.00-1.45) among those with no family history of PC. Results from this pilot study demonstrate differential sensitivity to PhIP among subgroups and therefore, this assay have potential as a susceptibility marker for prostate cancer risk.
AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been implicated in the development of colon, prostate and mammary gland tumors in rats. In this study, we developed a modified in vitro mutagen sensitivity assay, with activated PhIP (N-OH-PhIP) as the challenge mutagen and chromosome aberrations as the endpoint, and applied it in a pilot prostate cancer case-control study of 81 cases and 84 age and ethnicity-matched controls. Our results showed significantly higher baseline breaks among the cases, mean ± S.E. = 1.86 ± 0.23 versus 0.96 ± 0.14 in controls; P = 0.006. Individuals with high baseline breaks (dichotomized at the control median) had a 36% increased risk for PC (OR = 1.36; 95% CI = 1.08-1.72). In stratified analysis, high baseline breaks was associated in younger participants (≤60 years) with an OR of 1.71 (1.14-2.57) and in those with a positive family history of PC, an OR of 1.43 (0.97-2.11). PhIP treatment induced significantly higher breaks in cases, mean ± S.E. = 5.07 ± 0.39 versus 3.83 ± 0.24 in controls; P = 0.05. Higher PhIP-induced breaks was associated with an overall 17% increased risk for PC (OR = 1.17; 95% CI = 1.03-1.33), a significantly increased risks (OR = 1.19; 95% CI = 1.00-1.41) among younger participants, non-smokers (OR = 1.39, 1.03-1.88) and 1.20 (1.00-1.45) among those with no family history of PC. Results from this pilot study demonstrate differential sensitivity to PhIP among subgroups and therefore, this assay have potential as a susceptibility marker for prostate cancer risk.
KW - Peripheral blood lymphocytes
KW - PhIP
KW - Prostate cancer
KW - Susceptibility
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U2 - 10.1016/j.mrfmmm.2006.05.023
DO - 10.1016/j.mrfmmm.2006.05.023
M3 - Article
C2 - 16889804
AN - SCOPUS:33749528508
SN - 0027-5107
VL - 601
SP - 1
EP - 10
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -