Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis.

He, Jing

Xi, Bo

Ruiter, Rikje

Shi, Ting-Yan

Zhu, Mei-Ling

Wang, Meng-Yun

Li, Qiao-Xin

Zhou, Xiao-Yan

Qiu, Li-Xin

Wei, Qing-Yi

2019-02-01T15:15:36Z

2019-02-01T15:15:36Z

2013-01

2019-02-01T15:15:34Z

BACKGROUND: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. METHODS: We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities. RESULTS: The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. CONCLUSIONS: Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.

PONE-D-13-18360

1932-6203

1932-6203

https://hdl.handle.net/10161/17997

eng

Public Library of Science (PLoS)

PloS one

10.1371/journal.pone.0075135

Humans

Neoplasms

Prostatic Neoplasms

Genetic Predisposition to Disease

Leptin

RNA, Messenger

Case-Control Studies

Polymorphism, Single Nucleotide

Models, Genetic

Databases, Bibliographic

Continental Population Groups

Male

Receptors, Leptin

HapMap Project

Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis.

Journal article

Wei, Qing-Yi|0000-0002-3845-9445|0000-0003-4115-4439

e75135

10

School of Medicine

Duke

Duke Cancer Institute

Institutes and Centers

Population Health Sciences

Basic Science Departments

Medicine, Medical Oncology

Medicine

Clinical Science Departments

Published

8