Promoter polymorphisms and transcript levels of nicotinic receptor CHRNA5

Felicia S. Falvella, Antonella Galvan, Francesca Colombo, Elisa Frullanti, Ugo Pastorino, Tommaso A. Dragani

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Chromosomal locus 15q25, implicated in lung cancer risk and nicotine dependence, shows extensive linkage disequilibrium that complicates identification of causal variation. Cholinergic receptor nicotinic α5 (CHRNA5) has been identified as a lung cancer risk factor. We identified by sequence analysis three haplotypes (delTTC, insATC, and insTGG) in the 5′ promoter region and three at the 3′-untranslated region of CHRNA5. Linkage disequilibrium analysis of the 5′ variants showed that the insTGG haplotype is associated with three tightly linked risk alleles (nicotine dependence, lung cancer, and chronic obstructive pulmonary disease). The three CHRNA5 promoter haplotypes were statistically significantly associated with lung CHRNA5 transcript levels, determined by real-time polymerase chain reaction. In nontumor lung parenchyma from 68 patients who underwent lung lobectomy, the delTTC haplotype was associated with the highest CHRNA5 transcript levels (relative quantification units = 1.82), whereas the insTGG haplotype was associated with the lowest (0.88 units, Pdiff

Original languageEnglish
Pages (from-to)1366-1370
Number of pages5
JournalJournal of the National Cancer Institute
Volume102
Issue number17
DOIs
Publication statusPublished - Sep 8 2010

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Nicotinic Receptors
Haplotypes
Lung Neoplasms
Tobacco Use Disorder
Linkage Disequilibrium
Lung
3' Untranslated Regions
Cholinergic Receptors
Genetic Promoter Regions
Chronic Obstructive Pulmonary Disease
Sequence Analysis
Real-Time Polymerase Chain Reaction
Alleles

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Promoter polymorphisms and transcript levels of nicotinic receptor CHRNA5. / Falvella, Felicia S.; Galvan, Antonella; Colombo, Francesca; Frullanti, Elisa; Pastorino, Ugo; Dragani, Tommaso A.

In: Journal of the National Cancer Institute, Vol. 102, No. 17, 08.09.2010, p. 1366-1370.

Research output: Contribution to journalArticle

Falvella, Felicia S. ; Galvan, Antonella ; Colombo, Francesca ; Frullanti, Elisa ; Pastorino, Ugo ; Dragani, Tommaso A. / Promoter polymorphisms and transcript levels of nicotinic receptor CHRNA5. In: Journal of the National Cancer Institute. 2010 ; Vol. 102, No. 17. pp. 1366-1370.
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