Home > Research > Publications & Outputs > Association between genetic variants on chromos...
View graph of relations

Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. / Munafò, Marcus R.; Timofeeva, Maria N.; Morris, Richard W.; Prieto-Merino, David; Sattar, Naveed; Brennan, Paul; Johnstone, Elaine C.; Relton, Caroline; Johnson, Paul C. D.; Walther, Donna; Whincup, Peter H.; Casas, Juan P.; Uhl, George R.; Vineis, Paolo; Padmanabhan, Sandosh; Jefferis, Barbara J.; Amuzu, Antoinette; Riboli, Elio; Upton, Mark N.; Aveyard, Paul; Ebrahim, Shah; Hingorani, Aroon D.; Watt, Graham; Palmer, Tom M.; Timpson, Nicholas J.; Davey Smith, George; EPIC Study Group.

In: JNCI: Journal of the National Cancer Institute, Vol. 104, No. 10, 16.05.2012, p. 740-748.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Munafò, MR, Timofeeva, MN, Morris, RW, Prieto-Merino, D, Sattar, N, Brennan, P, Johnstone, EC, Relton, C, Johnson, PCD, Walther, D, Whincup, PH, Casas, JP, Uhl, GR, Vineis, P, Padmanabhan, S, Jefferis, BJ, Amuzu, A, Riboli, E, Upton, MN, Aveyard, P, Ebrahim, S, Hingorani, AD, Watt, G, Palmer, TM, Timpson, NJ, Davey Smith, G & EPIC Study Group 2012, 'Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure', JNCI: Journal of the National Cancer Institute, vol. 104, no. 10, pp. 740-748. https://doi.org/10.1093/jnci/djs191

APA

Munafò, M. R., Timofeeva, M. N., Morris, R. W., Prieto-Merino, D., Sattar, N., Brennan, P., Johnstone, E. C., Relton, C., Johnson, P. C. D., Walther, D., Whincup, P. H., Casas, J. P., Uhl, G. R., Vineis, P., Padmanabhan, S., Jefferis, B. J., Amuzu, A., Riboli, E., Upton, M. N., ... EPIC Study Group (2012). Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. JNCI: Journal of the National Cancer Institute, 104(10), 740-748. https://doi.org/10.1093/jnci/djs191

Vancouver

Munafò MR, Timofeeva MN, Morris RW, Prieto-Merino D, Sattar N, Brennan P et al. Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. JNCI: Journal of the National Cancer Institute. 2012 May 16;104(10):740-748. https://doi.org/10.1093/jnci/djs191

Author

Munafò, Marcus R. ; Timofeeva, Maria N. ; Morris, Richard W. ; Prieto-Merino, David ; Sattar, Naveed ; Brennan, Paul ; Johnstone, Elaine C. ; Relton, Caroline ; Johnson, Paul C. D. ; Walther, Donna ; Whincup, Peter H. ; Casas, Juan P. ; Uhl, George R. ; Vineis, Paolo ; Padmanabhan, Sandosh ; Jefferis, Barbara J. ; Amuzu, Antoinette ; Riboli, Elio ; Upton, Mark N. ; Aveyard, Paul ; Ebrahim, Shah ; Hingorani, Aroon D. ; Watt, Graham ; Palmer, Tom M. ; Timpson, Nicholas J. ; Davey Smith, George ; EPIC Study Group. / Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. In: JNCI: Journal of the National Cancer Institute. 2012 ; Vol. 104, No. 10. pp. 740-748.

Bibtex

@article{be8df5c0b6b0405fb88dafb42170d4ad,
title = "Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure",
abstract = "BACKGROUND: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.METHODS: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730-rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided.RESULTS: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730-rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10(-6)) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10(-11)). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730-rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42).CONCLUSIONS: Our data show a stronger association of rs1051730-rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.",
keywords = "Biological Markers, Chromosomes, Human, Pair 15, Cotinine, Gene Frequency, Humans, Linear Models, Linkage Disequilibrium, Lung Neoplasms, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Risk Factors, Smoking",
author = "Munaf{\`o}, {Marcus R.} and Timofeeva, {Maria N.} and Morris, {Richard W.} and David Prieto-Merino and Naveed Sattar and Paul Brennan and Johnstone, {Elaine C.} and Caroline Relton and Johnson, {Paul C. D.} and Donna Walther and Whincup, {Peter H.} and Casas, {Juan P.} and Uhl, {George R.} and Paolo Vineis and Sandosh Padmanabhan and Jefferis, {Barbara J.} and Antoinette Amuzu and Elio Riboli and Upton, {Mark N.} and Paul Aveyard and Shah Ebrahim and Hingorani, {Aroon D.} and Graham Watt and Palmer, {Tom M.} and Timpson, {Nicholas J.} and {Davey Smith}, George and {EPIC Study Group}",
year = "2012",
month = may,
day = "16",
doi = "10.1093/jnci/djs191",
language = "English",
volume = "104",
pages = "740--748",
journal = "JNCI: Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure

AU - Munafò, Marcus R.

AU - Timofeeva, Maria N.

AU - Morris, Richard W.

AU - Prieto-Merino, David

AU - Sattar, Naveed

AU - Brennan, Paul

AU - Johnstone, Elaine C.

AU - Relton, Caroline

AU - Johnson, Paul C. D.

AU - Walther, Donna

AU - Whincup, Peter H.

AU - Casas, Juan P.

AU - Uhl, George R.

AU - Vineis, Paolo

AU - Padmanabhan, Sandosh

AU - Jefferis, Barbara J.

AU - Amuzu, Antoinette

AU - Riboli, Elio

AU - Upton, Mark N.

AU - Aveyard, Paul

AU - Ebrahim, Shah

AU - Hingorani, Aroon D.

AU - Watt, Graham

AU - Palmer, Tom M.

AU - Timpson, Nicholas J.

AU - Davey Smith, George

AU - EPIC Study Group

PY - 2012/5/16

Y1 - 2012/5/16

N2 - BACKGROUND: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.METHODS: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730-rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided.RESULTS: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730-rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10(-6)) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10(-11)). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730-rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42).CONCLUSIONS: Our data show a stronger association of rs1051730-rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.

AB - BACKGROUND: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.METHODS: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730-rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided.RESULTS: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730-rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10(-6)) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10(-11)). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730-rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42).CONCLUSIONS: Our data show a stronger association of rs1051730-rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.

KW - Biological Markers

KW - Chromosomes, Human, Pair 15

KW - Cotinine

KW - Gene Frequency

KW - Humans

KW - Linear Models

KW - Linkage Disequilibrium

KW - Lung Neoplasms

KW - Odds Ratio

KW - Polymorphism, Single Nucleotide

KW - Receptors, Nicotinic

KW - Risk Factors

KW - Smoking

U2 - 10.1093/jnci/djs191

DO - 10.1093/jnci/djs191

M3 - Journal article

C2 - 22534784

VL - 104

SP - 740

EP - 748

JO - JNCI: Journal of the National Cancer Institute

JF - JNCI: Journal of the National Cancer Institute

SN - 0027-8874

IS - 10

ER -