A case-control study of a sex-specific association between a 15q25 variant and lung cancer risk.
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
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.
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
Chongjuan
C
Wei
Younghun
Y
Han
Margaret R
MR
Spitz
Xifeng
X
Wu
Haidee
H
Chancoco
Pinchas
P
Akiva
Gideon
G
Rechavi
Hadar
H
Brand
Issac
I
Wun
Marsha L
ML
Frazier
Christopher I
CI
Amos
D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D014481:United States / Q000453:epidemiology
D004273:DNA, Neoplasm