{"paper_id":"150e07cd-a717-465a-b8af-a8d563264792","body_text":"In the Spotlight\nNew Susceptibility\nLoci for Endometriosis\nMaria Rosa Maduro, PhD\nEndometriosis is an estrogen-dependent inflammatory disease\nthat is believed to affect 5 % to 10% of women of childbearing\nage. It can be a painful, debilitating disease that commonly\nleads to infertility.\nThe etiology(ies) of the disease has(ve) been hard to deter-\nmine. Therefore, efficient treatment and, certainly, prophylaxis\nhave not been successfully achieved.\nSince endometriosis is characterized by the presence of\nendometrium-like tissue outside of the uterine cavity, it has\nbeen hypothesized that fragments of menstrual endometrium\npass backward through the fallopian tubes to implant on perito-\nneal surfaces. This theory has, however, not been well received\nby all the experts in the field. However, the involvement of a\ngenetic factor to the disease has been generally well accepted\nand supported by hereditary studies.\nStudies on genetic variants on/around candidate genes have\nfailed to show strong associations with endometriosis. There-\nfore, to identify genes associated with endometriosis Uno et al\nhave performed the first genome-wide association study for this\ndisease and their results have recently been published in Nature\nGenetics (Nat. Genet, advance online publication, 1-4).\nUsing 1907 samples from Japanese individuals with endome-\ntriosis and 5292 controls, Uno and colleagues have been able to\nidentify a locus with significant association to endometriosis\nlocated on chromosome 9 at a region including the cyclin-\ndependent kinase inhibitor 2B antisense RNA, CDKN2BAS.\nFine single nucleotide polymorphisms (SNPs) mapping showed\nthat the strongest association was located in intron 16 of this\ngene, which is known to be expressed in the uterus and to be\nimplicated in the expression regulation of the tumor suppressor\ngenes p15, p16,a n d p14. The authors believe that the silencing\nof these tumor suppressor genes by CDKN2BAS might have a\nprominent role in the development of endometriosis.\nIn addition, Uno et al verified that a particular SNP,\nrs16826658, located in the LD block that includes WNT4\n(wingless-type MMTV integration site family, member 4) on\nchromosome 1, presented a possible association with endome-\ntriosis and may therefore be a candidate locus for endometrio-\nsis susceptibility. WNT4 is known to play a major role in the\ndevelopment of the female genital tract and to be expressed\nin the normal peritoneum. Thus, the authors hypothesize that\nendometriosis may arise through metaplasia using develop-\nmental pathways involved in the female genital tract.\nIn sum, the work presented by Uno et al certainly adds to the\nbetter understanding of endometriosis, providing insights into\nits pathology and raising hopes for new and more efficient\ntreatments.\nA Prophylactic Approach Against Breast\nCancer\nJaini et al have recently published on Nature Medicine (Nat.\nMed, 16(7), 799-803) a report on an autoimmune-mediated\nstrategy for breast cancer prevention involving vaccination that\nmay well revolutionize the way we look at this terrible disease.\nUp to now, cancer vaccine research has mostly focused on\nthe therapy against already established tumors, as the develop-\nment of prophylactic vaccines have been impaired by the diffi-\nculty of finding a tumor antigen that would not elicit profound\nautoimmune complications when used on a preventive vaccine\nsetting.\nJaini and colleagues seem to have successfully overcome\nthis problem in mouse, where they generated a breast-\nspecific a-lactalbumin antigen from lactating mammary tissue\nthat was later used for immunization. Since this mammary-\nspecific differentiation protein is highly expressed in breast\ncarcinomas, the observed immunoreactivity provided substan-\ntial protection and therapy against breast tumor growth in both\ntransgenic mouse models of breast cancer and transplanted\nbreast tumors. In addition, because a-lactalbumin is only\nexpressed in normal mammary epithelial cells during lactation,\nthe vaccination-induced prophylaxis was carried out without\nany detectable inflammatory reaction of normal nonlactating\ntissue.\nGiven the fact that several independent reports have con-\nfirmed that a-lactalbumin is expressed in the majority of\nhuman breast malignancies at levels sufficient for detection\nby immunocytochemical analysis, the authors speculate that\na-lactalbumin vaccination may provide a safe and effective\nprotection against breast cancer in postchildbearing women.\nIn sum, the data presented by Jaini et al provides experimen-\ntal support for the potential development of reliable and safe\nprotection, not only against breast cancer but also against other\ntumor types, by the targeted vaccination against tissue-specific\nand conditionally expressed protein antigens.\nReproductive Sciences\n17(10) 885\nª The Author(s) 2010\nReprints and permission:\nsagepub.com/journalsPermissions.nav\nDOI: 10.1177/1933719110383671\nhttp://rs.sagepub.com","source_license":"CC0","license_restricted":false}