Polymorphisms in CYP1A1 and ethnic-specific susceptibility to acute lymphoblastic leukemia in children

Ryan M. Swinney, Joke Beuten, Anderson B. Collier, Tina T L Chen, Naomi J. Winick, Bradley H Pollock, Gail E. Tomlinson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL. Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case-control analysis in Caucasian, Hispanic, and African-American children. Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18-5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43-7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27-5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13-5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40-7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P = 0.005). Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population. Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins.

Original languageEnglish (US)
Pages (from-to)1537-1542
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

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Cytochrome P-450 CYP1A1
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hispanic Americans
Alleles
Ethnic Groups
African Americans
Environmental Exposure
Registries
Leukemia
Epidemiology
Incidence

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Polymorphisms in CYP1A1 and ethnic-specific susceptibility to acute lymphoblastic leukemia in children. / Swinney, Ryan M.; Beuten, Joke; Collier, Anderson B.; Chen, Tina T L; Winick, Naomi J.; Pollock, Bradley H; Tomlinson, Gail E.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 7, 07.2011, p. 1537-1542.

Research output: Contribution to journalArticle

Swinney, Ryan M. ; Beuten, Joke ; Collier, Anderson B. ; Chen, Tina T L ; Winick, Naomi J. ; Pollock, Bradley H ; Tomlinson, Gail E. / Polymorphisms in CYP1A1 and ethnic-specific susceptibility to acute lymphoblastic leukemia in children. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 7. pp. 1537-1542.
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abstract = "Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL. Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case-control analysis in Caucasian, Hispanic, and African-American children. Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95{\%} CI 1.18-5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95{\%} CI 1.43-7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95{\%} CI 1.27-5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95{\%} CI 1.13-5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95{\%} CI 1.40-7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P = 0.005). Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population. Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins.",
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T1 - Polymorphisms in CYP1A1 and ethnic-specific susceptibility to acute lymphoblastic leukemia in children

AU - Swinney, Ryan M.

AU - Beuten, Joke

AU - Collier, Anderson B.

AU - Chen, Tina T L

AU - Winick, Naomi J.

AU - Pollock, Bradley H

AU - Tomlinson, Gail E.

PY - 2011/7

Y1 - 2011/7

N2 - Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL. Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case-control analysis in Caucasian, Hispanic, and African-American children. Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18-5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43-7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27-5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13-5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40-7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P = 0.005). Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population. Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins.

AB - Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL. Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case-control analysis in Caucasian, Hispanic, and African-American children. Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18-5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43-7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27-5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13-5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40-7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P = 0.005). Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population. Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins.

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