TY - JOUR
T1 - A case-control study of a sex-specific association between a 15q25 variant and lung cancer risk
AU - Wei, Chongjuan
AU - Han, Younghun
AU - Spitz, Margaret R.
AU - Wu, Xifeng
AU - Chancoco, Haidee
AU - Akiva, Pinchas
AU - Rechavi, Gideon
AU - Brand, Hadar
AU - Wun, Issac
AU - Frazier, Marsha L.
AU - Amos, Christopher I.
PY - 2011/12
Y1 - 2011/12
N2 - Background: Genetic variants located at 15q25, including those in the cholinergic receptor nicotinic cluster (CHRNA5) have been implicated in both lung cancer risk and nicotine dependence in recent genome-wide association studies. Among these variants, a 22-bp insertion/deletion, rs3841324 showed the strongest association with CHRNA5 mRNA expression levels. However the influence of rs3841324 on lung cancer risk has not been studied in depth. Methods: We have, therefore, evaluated the association of rs3841324 genotypes with lung cancer risk in a case-control study of 624 Caucasian subjects with lung cancer and 766 age- and sex-matched cancer-free Caucasian controls. We also evaluated the joint effects of rs3841324 with single-nucleotide polymorphisms (SNP) rs16969968 and rs8034191 in the 15q25 region that have been consistently implicated in lung cancer risk. Results: We found that the homozygous genotype with both short alleles (SS) of rs3841324 was associated with a decreased lung cancer risk in female ever smokers relative to the homozygous wild-type (LL) and heterozygous (LS) genotypes combined in a recessive model [OR adjusted = 0.55, 95% confidence interval (CI), 0.31-0.89, P = 0.0168]. There was no evidence for a sex difference in the association between this variant and cigarettes smoked per day (CPD). Diplotype analysis of rs3841324 with either rs16969968 or rs8034191 showed that these polymorphisms influenced the lung cancer risk independently. Conclusions and Impact: This study has shown a sex difference in the association between the 15q25 variant rs3841324 and lung cancers. Further research is warranted to elucidate the mechanisms underlying these observations.
AB - Background: Genetic variants located at 15q25, including those in the cholinergic receptor nicotinic cluster (CHRNA5) have been implicated in both lung cancer risk and nicotine dependence in recent genome-wide association studies. Among these variants, a 22-bp insertion/deletion, rs3841324 showed the strongest association with CHRNA5 mRNA expression levels. However the influence of rs3841324 on lung cancer risk has not been studied in depth. Methods: We have, therefore, evaluated the association of rs3841324 genotypes with lung cancer risk in a case-control study of 624 Caucasian subjects with lung cancer and 766 age- and sex-matched cancer-free Caucasian controls. We also evaluated the joint effects of rs3841324 with single-nucleotide polymorphisms (SNP) rs16969968 and rs8034191 in the 15q25 region that have been consistently implicated in lung cancer risk. Results: We found that the homozygous genotype with both short alleles (SS) of rs3841324 was associated with a decreased lung cancer risk in female ever smokers relative to the homozygous wild-type (LL) and heterozygous (LS) genotypes combined in a recessive model [OR adjusted = 0.55, 95% confidence interval (CI), 0.31-0.89, P = 0.0168]. There was no evidence for a sex difference in the association between this variant and cigarettes smoked per day (CPD). Diplotype analysis of rs3841324 with either rs16969968 or rs8034191 showed that these polymorphisms influenced the lung cancer risk independently. Conclusions and Impact: This study has shown a sex difference in the association between the 15q25 variant rs3841324 and lung cancers. Further research is warranted to elucidate the mechanisms underlying these observations.
UR - http://www.scopus.com/inward/record.url?scp=83055173327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=83055173327&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-11-0749
DO - 10.1158/1055-9965.EPI-11-0749
M3 - Article
C2 - 22028403
AN - SCOPUS:83055173327
SN - 1055-9965
VL - 20
SP - 2603
EP - 2609
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 12
ER -