2012年9月18日 訊 /生物谷BIOON/ --研究人員開展一項基因突變研究，這些突變提高婦女患上乳腺癌和卵巢癌的機率。他們的研究發現可能有助於開發出更便宜和更容易的方法來篩選乳腺癌和卵巢癌。此外，這些令人吃驚的研究發現可能也解釋著攜帶這些乳腺癌突變的人胚胎如何能夠存活下來。相關研究於近期刊登在PLoS ONE期刊上。
已知婦女的乳腺癌和卵巢癌易感基因BRCA1和BRCA2(BRCA1/2)能夠被用來預測她們患上這兩種癌症的風險。當基因BRCA1/2沒有發生突變時，她們在一生當中患上乳腺癌的機率是12%，患上卵巢癌的機率是1.4%。然而，當基因BRCA1/2發生突變時，她們患上乳腺癌的機率增加至12%，患上卵巢癌的機率增加至15-40%。
在當前這項研究中，參與研究的99名婦女攜帶BRCA1/2突變，而且她們幾乎全部還攜帶一種非常特異性的基因型：低水平的FMR1。相反，作為對照組的300多名婦女不攜帶BRCA1/2突變，而且她們當中除了只有大約25%的婦女具有較低水平的FMR1之外，其他人都表現出正常分布的FMR1基因型。研究人員作出結論，因為基因BRCA1/2突變是僅在攜帶低水平FMR1的婦女體內發現的，所以不攜帶低水平FMR1基因型的婦女將沒有發生基因BRCA1/2突變的風險，也就不與乳腺癌和卵巢癌相關聯。
低水平FMR1基因型與乳腺癌和卵巢癌相關聯，提示著人們能夠開發出一種更便宜的FMR1基因測試來替代當前昂貴的基因BRCA1/2突變篩選方法來確定婦女患上這兩種癌症的風險。
研究人員注意到對為什麼如此多的攜帶基因BRCA1/2突變的婦女也攜帶低水平FMR1基因型的最為可能的解釋就是，基因BRCA1/2突變對人胚胎是致命性的，除了這種基因突變之外，只有那些攜帶低水平FMR1基因型的胚胎才能夠存活下來。(生物谷Bioon.com)
BRCA1/2 Mutations Appear Embryo-Lethal Unless Rescued by Low (CGG n<26) FMR1 Sub-Genotypes: Explanation for the 「BRCA Paradox」?
Andrea Weghofer1,2, Muy-Kheng Tea3, David H. Barad1,4, Ann Kim1, Christian F. Singer3, Klaus Wagner5, Norbert Gleicher
BRCA1/2 mutations and recently described constitutional FMR1 genotypes have, independently, been associated with prematurely diminished ovarian reserve. Whether they interrelate in distribution, and whether observed effects of BRCA1/2 and FMR1 on ovaries are independent of each other, is unknown. In a prospective comparative cohort study, we, therefore, investigated the distribution of constitutional FMR1 genotypes, normal (norm), heterozygous (het) and homozygous (hom), and of their respective sub-genotypes (high/low), in 99 BRCA1/2 mutation-positive women and 410 female controls to determine whether distribution patterns differed between study and control patients. In contrast to controls, BRCA1/2 carriers demonstrated almost complete absence of all constitutional FMR1 genotypes except for sub-genotypes with low (CGG n<26) alleles. Cross tabulation between BRCA1/2-positive patients and controls confirmed significant group membership, related to FMR1 distribution (P<0.0001). These results offer as most likely explanation the conclusion that BRCA1/2 mutations are embryo-lethal, unless rescued by low (CGG n<26) FMR1 sub-genotypes, present in approximately one quarter of all women. Women with low FMR1 sub-genotypes, therefore, should reflect increased BRCA1/2-associated cancer risks, while the remaining approximately 75 percent should face almost no such risks. If confirmed, this observation offers opportunities for more efficient and less costly BRCA1/2 cancer screening. The study also suggests that previously reported risk towards prematurely diminished ovarian reserve in association with BRCA mutations is FMR1-mediated, and offers a possible explanation for the so-called 「BRCA paradox」 by raising the possibility that the widely perceived BRCA1/2-associated tumor risk is actually FMR1-mediated.