CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification

Melinda C. Aldrich, Steve Selvin, Helen M. Hansen, Lisa F. Barcellos, Margaret R. Wrensch, Jennette D. Sison, Karl T. Kelsey, Patricia A. Buffler, Charles P. Quesenberry, Michael F Seldin, John K. Wiencke

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Prior studies of lung cancer and CYP1A1/2 in African- American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of cyiia1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998-2003). African- Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28-3.19 and OR, 0.55; 95% CI, 0.36-0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos.

Original languageEnglish (US)
Pages (from-to)2340-2348
Number of pages9
JournalCancer Research
Volume69
Issue number6
DOIs
StatePublished - Mar 15 2009

Fingerprint

Cytochrome P-450 CYP1A1
Hispanic Americans
Haplotypes
Lung Neoplasms
African Americans
Population
Odds Ratio
Confidence Intervals
Cytochrome P-450 CYP1A2
Gene Frequency
Single Nucleotide Polymorphism
Case-Control Studies
Smoking

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aldrich, M. C., Selvin, S., Hansen, H. M., Barcellos, L. F., Wrensch, M. R., Sison, J. D., ... Wiencke, J. K. (2009). CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification. Cancer Research, 69(6), 2340-2348. https://doi.org/10.1158/0008-5472.CAN-08-2576

CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification. / Aldrich, Melinda C.; Selvin, Steve; Hansen, Helen M.; Barcellos, Lisa F.; Wrensch, Margaret R.; Sison, Jennette D.; Kelsey, Karl T.; Buffler, Patricia A.; Quesenberry, Charles P.; Seldin, Michael F; Wiencke, John K.

In: Cancer Research, Vol. 69, No. 6, 15.03.2009, p. 2340-2348.

Research output: Contribution to journalArticle

Aldrich, MC, Selvin, S, Hansen, HM, Barcellos, LF, Wrensch, MR, Sison, JD, Kelsey, KT, Buffler, PA, Quesenberry, CP, Seldin, MF & Wiencke, JK 2009, 'CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification', Cancer Research, vol. 69, no. 6, pp. 2340-2348. https://doi.org/10.1158/0008-5472.CAN-08-2576
Aldrich MC, Selvin S, Hansen HM, Barcellos LF, Wrensch MR, Sison JD et al. CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification. Cancer Research. 2009 Mar 15;69(6):2340-2348. https://doi.org/10.1158/0008-5472.CAN-08-2576
Aldrich, Melinda C. ; Selvin, Steve ; Hansen, Helen M. ; Barcellos, Lisa F. ; Wrensch, Margaret R. ; Sison, Jennette D. ; Kelsey, Karl T. ; Buffler, Patricia A. ; Quesenberry, Charles P. ; Seldin, Michael F ; Wiencke, John K. / CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification. In: Cancer Research. 2009 ; Vol. 69, No. 6. pp. 2340-2348.
@article{4f4aee76d39648698a5e98bb24530384,
title = "CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification",
abstract = "Prior studies of lung cancer and CYP1A1/2 in African- American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of cyiia1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998-2003). African- Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95{\%} confidence interval (95{\%} CI), 1.28-3.19 and OR, 0.55; 95{\%} CI, 0.36-0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos.",
author = "Aldrich, {Melinda C.} and Steve Selvin and Hansen, {Helen M.} and Barcellos, {Lisa F.} and Wrensch, {Margaret R.} and Sison, {Jennette D.} and Kelsey, {Karl T.} and Buffler, {Patricia A.} and Quesenberry, {Charles P.} and Seldin, {Michael F} and Wiencke, {John K.}",
year = "2009",
month = "3",
day = "15",
doi = "10.1158/0008-5472.CAN-08-2576",
language = "English (US)",
volume = "69",
pages = "2340--2348",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - CYP1A1/2 haplotypes and lung cancer and assessment of confounding by population stratification

AU - Aldrich, Melinda C.

AU - Selvin, Steve

AU - Hansen, Helen M.

AU - Barcellos, Lisa F.

AU - Wrensch, Margaret R.

AU - Sison, Jennette D.

AU - Kelsey, Karl T.

AU - Buffler, Patricia A.

AU - Quesenberry, Charles P.

AU - Seldin, Michael F

AU - Wiencke, John K.

PY - 2009/3/15

Y1 - 2009/3/15

N2 - Prior studies of lung cancer and CYP1A1/2 in African- American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of cyiia1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998-2003). African- Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28-3.19 and OR, 0.55; 95% CI, 0.36-0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos.

AB - Prior studies of lung cancer and CYP1A1/2 in African- American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of cyiia1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998-2003). African- Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28-3.19 and OR, 0.55; 95% CI, 0.36-0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos.

UR - http://www.scopus.com/inward/record.url?scp=65549122189&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549122189&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-2576

DO - 10.1158/0008-5472.CAN-08-2576

M3 - Article

C2 - 19276377

AN - SCOPUS:65549122189

VL - 69

SP - 2340

EP - 2348

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 6

ER -