Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk

Nora L. Nock, Xin Liu, Mine Cicek, Li Li, Flavius Macarie, Benjamin A. Rybicki, Sarah J. Plummer, Gregory T. MacLennan, Graham Casey, John S. Witte

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The relationship between cigarette smoking and prostate cancer remains unclear. Any potential association may depend on the individuals' ability to metabolize and detoxify cigarette carcinogens - such as polycyclic aromatic hydrocarbons. To investigate this, we studied the association between prostate cancer and smoking, as well as the main and modifying effects of functional polymorphisms in genes that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile462Val, microsomal epoxide hydrolase His139Arg) and detoxify reactive derivatives (GSTM1 null deletion, GSTT1 null deletion, GSTP1 Ile105Val and Ala114Val) using a family-based case-control design (439 prostate cancer cases and 479 brother controls). Within the entire study population, there were no main effects for smoking or any of the polymorphisms. However, the nondeleted GSTM1 allele was inversely associated with prostate cancer [odds ratio (OR), 0.50; 95% confidence interval (95% CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7 and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95% CI, 1.01-2.79) with prostate cancer in men with more aggressive disease (Gleason score ≥ 7 or clinical tumor stage ≥ T2c). We also found a statistically significant negative multiplicative interaction between the GSTM1 nondeleted allele and heavy smoking (> 20 pack-years) in the total study population (P = 0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR, 1.73; 95% CI, 0.99-3.05) but this increased risk was not observed in heavy smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95% CI, 0.53-1.71). Our results highlight the importance of considering genetic modifiers of carcinogens when evaluating smoking in prostate cancer.

Original languageEnglish (US)
Pages (from-to)756-761
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

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Polycyclic Aromatic Hydrocarbons
Prostatic Neoplasms
Smoking
Genes
Odds Ratio
Confidence Intervals
Carcinogens
Alleles
Epoxide Hydrolases
Cytochrome P-450 CYP1A1
Aptitude
Neoplasm Grading
Tobacco Products
Population
Siblings
Genotype

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk. / Nock, Nora L.; Liu, Xin; Cicek, Mine; Li, Li; Macarie, Flavius; Rybicki, Benjamin A.; Plummer, Sarah J.; MacLennan, Gregory T.; Casey, Graham; Witte, John S.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 15, No. 4, 04.2006, p. 756-761.

Research output: Contribution to journalArticle

Nock, Nora L. ; Liu, Xin ; Cicek, Mine ; Li, Li ; Macarie, Flavius ; Rybicki, Benjamin A. ; Plummer, Sarah J. ; MacLennan, Gregory T. ; Casey, Graham ; Witte, John S. / Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk. In: Cancer Epidemiology Biomarkers and Prevention. 2006 ; Vol. 15, No. 4. pp. 756-761.
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abstract = "The relationship between cigarette smoking and prostate cancer remains unclear. Any potential association may depend on the individuals' ability to metabolize and detoxify cigarette carcinogens - such as polycyclic aromatic hydrocarbons. To investigate this, we studied the association between prostate cancer and smoking, as well as the main and modifying effects of functional polymorphisms in genes that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile462Val, microsomal epoxide hydrolase His139Arg) and detoxify reactive derivatives (GSTM1 null deletion, GSTT1 null deletion, GSTP1 Ile105Val and Ala114Val) using a family-based case-control design (439 prostate cancer cases and 479 brother controls). Within the entire study population, there were no main effects for smoking or any of the polymorphisms. However, the nondeleted GSTM1 allele was inversely associated with prostate cancer [odds ratio (OR), 0.50; 95{\%} confidence interval (95{\%} CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7 and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95{\%} CI, 1.01-2.79) with prostate cancer in men with more aggressive disease (Gleason score ≥ 7 or clinical tumor stage ≥ T2c). We also found a statistically significant negative multiplicative interaction between the GSTM1 nondeleted allele and heavy smoking (> 20 pack-years) in the total study population (P = 0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR, 1.73; 95{\%} CI, 0.99-3.05) but this increased risk was not observed in heavy smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95{\%} CI, 0.53-1.71). Our results highlight the importance of considering genetic modifiers of carcinogens when evaluating smoking in prostate cancer.",
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AU - Macarie, Flavius

AU - Rybicki, Benjamin A.

AU - Plummer, Sarah J.

AU - MacLennan, Gregory T.

AU - Casey, Graham

AU - Witte, John S.

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