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Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.

ABSTRACT: BACKGROUND:Single nucleotide polymorphisms (SNPs) in 3'-untranslated region (UTR) of genes related with cell-matrix adhesions and migration might affect miRNA binding and potentially affect the risk of cancer. The present study aimed to screen SNPs in 3' UTR of cancer-related genes and investigate their contribution to the susceptibility of lung cancer. METHODS:Seven SNPs were selected and genotyped in a case-control study (322 lung cancer patients and 384 controls) among Chinese Han population. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender in multiple genetic models. RESULTS:In stratified analyses by gender, three (rs1064607, rs3796283 and rs2378456) of LPP gene were associated with a significantly increased susceptibility for lung cancer among male population. Besides, LPP rs2378456 weakened lung cancer risk in female. LPP rs1064607 polymorphism was significantly correlated with increased risk of lung adenocarcinoma. Furthermore, AA genotype of TNS3 rs9876 polymorphism was associated with lymphatic metastasis. CONCLUSION:Our results provides evidence for the impact of LPP polymorphisms on the susceptibility to lung cancer in Chinese population.

SUBMITTER: Yan S

PROVIDER: S-EPMC6325744 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.

Yan Shouchun S Sun Rong R Wu Shan S Jin Tianbo T Zhang Shanshan S Niu Fanglin F Li Jingjie J Chen Mingwei M

BMC cancer 20190108 1

<h4>Background</h4>Single nucleotide polymorphisms (SNPs) in 3'-untranslated region (UTR) of genes related with cell-matrix adhesions and migration might affect miRNA binding and potentially affect the risk of cancer. The present study aimed to screen SNPs in 3' UTR of cancer-related genes and investigate their contribution to the susceptibility of lung cancer.<h4>Methods</h4>Seven SNPs were selected and genotyped in a case-control study (322 lung cancer patients and 384 controls) among Chinese ...[more]

PMID: 30621612

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Project description:Osteonectin/SPARC is one of the most abundant noncollagenous extracellular matrix proteins in bone, regulating collagen fiber assembly and promoting osteoblast differentiation. Osteonectin-null and haploinsufficient mice have low-turnover osteopenia, indicating that osteonectin contributes to normal bone formation. In male idiopathic osteoporosis patients, osteonectin 3' untranslated region (UTR) single-nucleotide polymorphism (SNP) haplotypes that differed only at SNP1599 (rs1054204) were previously associated with bone mass. Haplotype A (containing SNP1599G) was more frequent in severely affected patients, whereas haplotype B (containing SNP1599C) was more frequent in less affected patients and healthy controls. We hypothesized that SNP1599 contributes to variability in bone mass by modulating osteonectin levels. Osteonectin 3' UTR reporter constructs demonstrated that haplotype A has a repressive effect on gene expression compared with B. We found that SNP1599G contributed to an miR-433 binding site, and miR-433 inhibitor relieved repression of the haplotype A, but not B, 3' UTR reporter construct. We tested our hypothesis in vivo, using a knock-in approach to replace the mouse osteonectin 3' UTR with human haplotype A or B 3' UTR. Compared with haplotype A mice, bone osteonectin levels were higher in haplotype B mice. B mice displayed higher bone formation rate and gained more trabecular bone with age. When parathyroid hormone was administered intermittently, haplotype B mice gained more cortical bone area than A mice. Cultured marrow stromal cells from B mice deposited more mineralized matrix and had higher osteocalcin mRNA compared with A mice, demonstrating a cell-autonomous effect on differentiation. Altogether, SNP1599 differentially regulates osteonectin expression and contributes to variability in bone mass, by a mechanism that may involve differential targeting by miR-433. This work validates the findings of the previous candidate gene study, and it assigns a physiological function to a common osteonectin allele, providing support for its role in the complex trait of skeletal phenotype. © 2014 American Society for Bone and Mineral Research.

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Dataset Information

Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.

Publications

Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.

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