生物谷報道：美國西北紀(jì)念醫(yī)院的腫瘤專家最近發(fā)表報告稱,，脂聯(lián)素基因的變異很可能增加女性患乳腺癌的風(fēng)險，這將成為目前發(fā)現(xiàn)的與乳腺癌相關(guān)聯(lián)的第三個基因,。研究論文發(fā)表在新一期Cancer Research雜志上,。
脂聯(lián)素基因可以調(diào)控很多新陳代謝過程,，有些女性在出生時，她們體內(nèi)的脂聯(lián)素基因就帶有不同特性,，會改變基因的功能,，從而增加乳腺癌的發(fā)病幾率。這一發(fā)現(xiàn)與先前關(guān)于體內(nèi)脂聯(lián)素含量低將會增加癌癥風(fēng)險的研究結(jié)果相一致,。如果其他輔助研究也得到證實(shí),，脂聯(lián)素將和已經(jīng)發(fā)現(xiàn)的另兩個基因——TGF-beta和CHEK2——共同創(chuàng)造一個基因檢測模式，這一模式將幫助臨床學(xué)家更準(zhǔn)確地預(yù)測乳腺癌的患病風(fēng)險,。
目前，臨床學(xué)家只能依賴流行病模式的診斷來檢測乳腺癌,，最常用的模式是“GAIL”模式,，它通過測試包括女性年齡、月經(jīng)起始年齡,、絕經(jīng)年齡,、首次生育年齡、活體組織檢查切片以及家族病史在內(nèi)的諸多因素來測定女性乳腺癌的患病幾率,?；蛟\斷已被用于有乳腺癌家族史的檢測，以鑒定乳腺癌遺傳與BRCA基因是否存在關(guān)聯(lián),。然而,，每年確診的大多數(shù)乳腺癌患者都沒有家族病史，這使得大量的乳腺癌病例無法解釋和預(yù)測,。
卡克拉馬尼說：“據(jù)我們所知,，1/8的女性患上乳腺癌很可能是受基因影響，脂聯(lián)素基因就是其中一個可能的誘發(fā)基因,。通過明確哪些基因與乳腺癌患病相關(guān)聯(lián),，我們就能更好地預(yù)測風(fēng)險，并最終致力于預(yù)防癌癥,。我們希望通過進(jìn)一步的研究,，有朝一日能利用基因診斷的方法，使所有女性都能預(yù)先了解自己患乳腺癌的風(fēng)險,，而那些有較高患病風(fēng)險的人,，就可以與他們的理療師共同采取防患措施，達(dá)到最佳預(yù)防效果,，我們正朝著這個方向努力,。”（生物谷www.bioon.com)
生物谷推薦原始出處：
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 with diabetes. Adiponectin is a protein exclusively secreted by adipose tissue, circulating levels of which have been associated with breast cancer risk. Whether genetic variants within the adiponectin pathway are associated with breast cancer risk is unknown. To explore the association of genetic variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with breast cancer risk, we conducted a case control study of female patients with breast cancer and healthy female controls from New York City recruited between 1999 and 2004. We genotyped 733 hospital-based breast cancer cases and 839 controls for 10 haplotype-tagging single nucleotide polymorphisms (SNP) of ADIPOQ and ADIPOR1. Two ADIPOQ SNPs (rs2241766 and rs1501299), which have been associated with circulating levels of adiponectin, were associated with breast 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, was also associated with breast cancer risk (OR, 0.51; 95% CI, 0.28–0.92). Based on the known function of rs2241766 and rs1501299, we categorized individuals by adiponectin signaling status and found that, when compared with high signalers, intermediate signalers had a 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 cancer risk (95% CI, 0.78–54.89; Ptrend = 0.001). This is the first report of an association between functionally relevant variants of the adiponectin pathway and breast cancer risk. The results warrant further studies of the adiponectin pathway in breast cancer. [Cancer Res 2008;68(9):3178–83]
