Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.
Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.
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DOI：
10.1007/s10549-009-0503-1
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发表时间：
2010-04
影响因子：
3.8
通讯作者：
Santella, Regina M.
中科院分区：
文献类型：
--
作者：
Cleveland, Rebecca J.;Gammon, Marilie D.;Long, Chang-Min;Gaudet, Mia M.;Eng, Sybil M.;Teitelbaum, Susan L.;Neugut, Alfred I.;Santella, Regina M.
肥胖是绝经后妇女患乳腺癌的一个强有力的危险因素，也是与绝经状态无关的不良预后指标。瘦素是脂肪组织质量的重要调节剂，并且与肿瘤细胞生长相关。瘦素通过与瘦素受体（LEPR）相互作用发挥其作用。我们调查了瘦素（LEP）和LEPR基因的遗传变异是否与乳腺癌的风险相关，或者一旦确诊，与生存率相关。LEP G-2548 A和LEPR Q223 R多态性在以人群为基础的研究中进行了表征，该研究主要由欧洲-美国女性组成。该研究调查了1996年至1997年期间被诊断为第一次原发性浸润性乳腺癌的1,065名妇女。对照组为1,108名妇女，按5岁年龄组与病例频率相匹配。与LEP-2548 GG基因型相比，LEP-2548 AA基因型与乳腺癌发生风险的适度增加相关（年龄调整OR=1.30; 95%CI =1.01-1.66）。这种关联在肥胖的绝经后妇女中更强（OR=1.86; 95%CI =0.95-3.64），尽管相互作用具有边缘统计学意义（P=0.07）。我们没有发现LEP或LEPR多态性与乳腺癌妇女全因死亡率或乳腺癌特异性死亡率相关的证据（平均随访时间=66.7个月）。当按绝经状态分层时，这些基因型对乳腺癌风险和死亡率的影响没有显著差异。总之，我们的研究结果表明，LEP的一个常见变异可能与乳腺癌的发病风险有关，支持瘦素参与乳腺癌发生的假设。
Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR=1.30; 95% CI=1.01–1.66). This association was stronger among postmenopausal women who were obese (OR=1.86; 95% CI=0.95–3.64) although the interaction was of borderline statistical significance (P=0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time=66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.
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影响因子：
3.2
作者：
Gómez, JM;Maravall, FJ;Soler, J
通讯作者：
Soler, J
影响因子：
3.8
作者：
Loi, S;Milne, RL;Phillips, KA
通讯作者：
Phillips, KA
影响因子：
9.8
作者：
Ogawa, T;Hirose, H;Saruta, T
通讯作者：
Saruta, T
影响因子：
82.9
作者：
HAMILTON, BS;PAGLIA, D;DEITEL, M
通讯作者：
DEITEL, M
影响因子：
45.3
作者：
Goodwin, PJ;Ennis, M;Hood, N
通讯作者：
Hood, N