Genetic polymorphisms in obesity-related genes and endometrial cancer risk.
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.
Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee 37203-1738, USA.
Xiaoli
X
Chen
Yong-Bing
YB
Xiang
Ji-Rong
JR
Long
Hui
H
Cai
Qiuyin
Q
Cai
Jiarong
J
Cheng
Wanqing
W
Wen
Yu-Tang
YT
Gao
Wei
W
Zheng
Xiao-Ou
XO
Shu
D052242:Adiponectin / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020738:Leptin / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics*; D054411:Receptors, Leptin / Q000235:genetics; D012307:Risk Factors
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D020738:Leptin; D054419:Receptors, Adiponectin; D054411:Receptors, Leptin