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Genetic polymorphisms in obesity‐related genes and endometrial cancer risk
Author(s) -
Chen Xiaoli,
Xiang YongBing,
Long JiRong,
Cai Hui,
Cai Qiuyin,
Cheng Jiarong,
Wen Wanqing,
Gao YuTang,
Zheng Wei,
Shu XiaoOu
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26552
Subject(s) - single nucleotide polymorphism , adiponectin , minor allele frequency , medicine , endometrial cancer , linkage disequilibrium , odds ratio , allele , endocrinology , body mass index , leptin , haplotype , leptin receptor , obesity , genotype , genetics , cancer , biology , gene , insulin resistance
BACKGROUND: Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin ( ADIPOQ ), leptin ( LEP ), adiponectin receptor 1 ( ADIPOR1 ), adiponectin receptor 2 ( ADIPOR2 ), and leptin receptor ( LEPR ) are associated with endometrial cancer. METHODS: The authors selected 87 tagging SNPs to capture common genetic variants in these 5 genes. These SNPs were evaluated in 1028 endometrial cancer cases and 1932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI, 0.48‐0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ , which were in linkage disequilibrium with rs3774262. These associations became nonsignificant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, smaller waist and hip circumferences, and lower body mass index than controls with the major allele G (all P < .05). Women homozygous for the minor allele (T/T) of rs2071045 in the LEP gene also had significantly lower risk (OR, 0.70; 95% CI, 0.54‐0.90) than women homozygous for the major allele (C/C). No other SNPs in the LEP, ADIPOR1 , ADIPOR2 , or LEPR genes were found to be associated with cancer risk. CONCLUSIONS: Although a chance finding cannot be ruled out, the consistency of findings for gene‐endometrial cancer risk and gene‐obesity measurements suggests that genetic polymorphisms in the ADIPOQ gene may play a role in endometrial cancer development. Cancer 2011. © 2011 American Cancer Society.