美国西北纪念医院的肿瘤专家最近发表报告称，脂联素基因的变异很可能增加女性患乳腺癌的风险，这将成为目前发现的与乳腺癌相关联的第三个基因。研究论文发表在新一期Cancer Research杂志上。

脂联素基因可以调控很多新陈代谢过程，有些女性在出生时，她们体内的脂联素基因就带有不同特性，会改变基因的功能，从而增加乳腺癌的发病几率。这一发现与先前关于体内脂联素含量低将会增加癌症风险的研究结果相一致。如果其他辅助研究也得到证实，脂联素将和已经发现的另两个基因——TGF-beta和CHEK2——共同创造一个基因检测模式，这一模式将帮助临床学家更准确地预测乳腺癌的患病风险。

目前，临床学家只能依赖流行病模式的诊断来检测乳腺癌，最常用的模式是“GAIL”模式，它通过测试包括女性年龄、月经起始年龄、绝经年龄、首次生育年龄、活体组织检查切片以及家族病史在内的诸多因素来测定女性乳腺癌的患病几率。基因诊断已被用于有乳腺癌家族史的检测，以鉴定乳腺癌遗传与BRCA基因是否存在关联。然而，每年确诊的大多数乳腺癌患者都没有家族病史，这使得大量的乳腺癌病例无法解释和预测。

卡克拉马尼说：“据我们所知，1/8的女性患上乳腺癌很可能是受基因影响，脂联素基因就是其中一个可能的诱发基因。通过明确哪些基因与乳腺癌患病相关联，我们就能更好地预测风险，并最终致力于预防癌症。我们希望通过进一步的研究，有朝一日能利用基因诊断的方法，使所有女性都能预先了解自己患乳腺癌的风险，而那些有较高患病风险的人，就可以与他们的理疗师共同采取防患措施，达到最佳预防效果，我们正朝着这个方向努力。”

原始出处：Cancer Research，68, 3178-3184, May 1, 2008. doi: 10.1158/0008-5472，Virginia G. Kaklamani, Christos Mantzoros

Variants of the Adiponectin and Adiponectin Receptor 1 Genes and Breast Cancer Risk

Virginia G. Kaklamani1, Maureen Sadim1, Alex Hsi3, Kenneth Offit4, Carole Oddoux5, Harry Ostrer5, Habibul Ahsan2, Boris Pasche1 and Christos Mantzoros3

1 Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University; 2 Department of Health Studies, Medicine and Human Genetics, University of Chicago, Chicago, Illinois; 3 Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; 4 Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center; and 5 Human Genetics Program, Department of Pediatrics, New York University Medical Center, New York, New York

Breast cancer risk is higher among obese women and women withdiabetes. Adiponectin is a protein exclusively secreted by adiposetissue, circulating levels of which have been associated withbreast cancer risk. Whether genetic variants within the adiponectinpathway are associated with breast cancer risk is unknown. Toexplore the association of genetic variants of the adiponectin(ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with breastcancer risk, we conducted a case control study of female patientswith breast cancer and healthy female controls from New YorkCity recruited between 1999 and 2004. We genotyped 733 hospital-basedbreast cancer cases and 839 controls for 10 haplotype-taggingsingle nucleotide polymorphisms (SNP) of ADIPOQ and ADIPOR1.Two ADIPOQ SNPs (rs2241766 and rs1501299), which have been associatedwith circulating levels of adiponectin, were associated withbreast cancer risk [rs1501299*GG: odd ratios (OR), 1.80; 95%confidence interval (95% CI), 1.14–2.85; rs2241766*TG:OR, 0.61; 95% CI, 0.46–0.80]. One ADIPOR1 SNP (rs7539542),which modulates expression of adiponectin receptor 1 mRNA, wasalso associated with breast cancer risk (OR, 0.51; 95% CI, 0.28–0.92).Based on the known function of rs2241766 and rs1501299, we categorizedindividuals by adiponectin signaling status and found that,when compared with high signalers, intermediate signalers hada 4.16-fold increase in breast cancer risk (95% CI, 0.49–35.19),and low signalers had a 6.56-fold increase in breast cancerrisk (95% CI, 0.78–54.89; Ptrend = 0.001). This is thefirst report of an association between functionally relevantvariants of the adiponectin pathway and breast cancer risk.The results warrant further studies of the adiponectin pathwayin breast cancer. [Cancer Res 2008;68(9):3178–83]