The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.
The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.
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DOI：
10.1371/journal.pone.0016756
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发表时间：
2011-02-08
期刊：
影响因子：
3.7
通讯作者：
Goodman MT
中科院分区：
文献类型：
--
作者：
Lurie G;Gaudet MM;Spurdle AB;Carney ME;Wilkens LR;Yang HP;Weiss NS;Webb PM;Thompson PJ;Terada K;Setiawan VW;Rebbeck TR;Prescott J;Orlow I;O'Mara T;Olson SH;Narod SA;Matsuno RK;Lissowska J;Liang X;Levine DA;Le Marchand L;Kolonel LN;Henderson BE;Garcia-Closas M;Doherty JA;De Vivo I;Chen C;Brinton LA;Akbari MR;Australian National Endometrial Cancer Study Group;Epidemiology of Endometrial Cancer Consortium (E2C2);Goodman MT
超重和肥胖与子宫内膜癌密切相关。几项独立的全基因组关联研究最近发现了两种常见的多态性，FTO rs 9939609和MC 4 R rs 17782313，它们与体重增加和肥胖有关。我们在子宫内膜癌流行病学联合会（E2 C2）的9项病例对照研究的汇总分析中研究了FTO rs 9939609和MC 4 R rs 17782313与子宫内膜癌风险的关系。该分析包括3601名非西班牙裔白色妇女与组织学证实的子宫内膜癌和5275频率匹配的对照。采用非条件Logistic回归模型评估FTO rs 9939609和MC 4 R rs 17782313基因型与子宫内膜癌风险的关系。在对照组女性中，FTO rs 9939609 A和MC 4 R rs 17782313 C等位基因均与超重风险增加16%相关（分别为p= 0.001和p =0.004）。 在病例对照分析中，FTO rs 9939609 AA基因型携带者与TT基因型携带者相比，患子宫内膜癌的风险增加[比值比（OR）= 1.17; 95%置信区间（CI）：1.03-1.32，p = 0.01]。 然而，在调整体重指数（BMI）后，这种关联不再明显，表明基因-疾病效应通过体重介导。MC 4 R rs 17782313多态性与子宫内膜癌风险无关（每个等位基因OR = 0.98; 95%CI：0.91-1.06; p = 0.68）。 FTO rs 9939609是子宫内膜癌风险较高的白色非西班牙裔女性的易感性标志物。虽然FTO rs 9939609单独可能有有限的临床或公共卫生意义，以确定妇女在子宫内膜癌的高风险超出超重，肥胖相关的遗传标记的进一步调查可能有助于确定影响子宫内膜癌发生的途径。
Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.
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影响因子：
158.5
作者：
Cecil, Joanne E.;Tavendale, Roger;Palmer, Colin N. A.
通讯作者：
Palmer, Colin N. A.
DOI：
10.1016/j.jsbmb.2007.09.020
发表时间：
2008-02-01
影响因子：
4.1
作者：
Doll, A.;Abal, M.;Reventos, J.
通讯作者：
Reventos, J.
影响因子：
30.8
作者：
Chambers, John C.;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
影响因子：
6.9
作者：
Speakman, John R.;Rance, Kellie A.;Johnstone, Alexandra M.
通讯作者：
Johnstone, Alexandra M.
DOI：
10.1159/000264407
发表时间：
2010-01-01
期刊：
FRONTIERS IN EATING AND WEIGHT REGULATION
影响因子：
--
作者：
Hetherington, Marion M.;Cecil, Joanne E.
通讯作者：
Cecil, Joanne E.