Low-density lipoprotein receptor-related protein 6 (LRP6) rs10845498 polymorphism is associated with a decreased risk of non-small cell lung cancer.
OBJECTIVE
Low-density lipoprotein receptor-related protein 6 (LRP6) modulates Wnt signaling transduction. Altered LRP6 expression leads to abnormal Wnt protein activation, cell proliferation and tumorigenesis. This study investigated the association between LRP6 single-nucleotide polymorphisms (SNPs) and non-small-cell lung cancer (NSCLC) in a Chinese population.


METHODS
A total of 500 NSCLC patients and 500 healthy controls were recruited for assessment of four LRP6 SNPs using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses.


RESULTS
The frequency of the LRP6 rs10845498 genotype was 60.9% (A/A), 35.5% (AG) and 3.6% (GG) in patients with lung squamous cell carcinoma (SCC) and 69.2% (A/A), 27.2% (A/G) and 3.6% (GG) in controls. Logistic regression analysis revealed that the LRP6 rs10845498 A/A major allele was associated with a reduced risk in developing lung SCC (OR = 0.69; 95% CI, 0.48-1.00; P=0.04), and tobacco smokers had a 2.21 fold greater risk in developing SCC than nonsmokers (p<0.01, 95% CI, 1.72-2.85), and tobacco smokers who carried an "A" allele (AA+AG) in rs6488507 had a 2.34-fold greater risk in developing NSCLC than other patients (p< 0.01, 95%CI, 1.74-3.13).


CONCLUSIONS
The LRP6 rs10845498 SNP is associated with a reduced risk of lung SCC, while tobacco smoke increases the risk. LRP6 rs6488507 polymorphism synergistically increased the risk of NSCLC in tobacco smokers. Further studies are needed to elucidate the functional impact of LRP6 expression and activity in NSCLC.
1. Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou 310022, China; ; 2. The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310035, China.
Dehou
D
Deng
1. Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou 310022, China;
Yongjun
Y
Zhang
1. Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou 310022, China;
Wenglong
W
Bao
1. Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou 310022, China;
Xiangming
X
Kong
D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6
Non-small cell lung cancer; genetic susceptibility; low-density lipoprotein receptor-related protein 6; single nucleotide polymorphism.