2011年,，全球估計(jì)有225,500名卵巢癌患者新增病例,。眾所周知慢性炎癥會(huì)影響多種惡性腫瘤的發(fā)生及發(fā)展,，其中就包括卵巢癌,。由于炎癥在多種癌癥類型中發(fā)揮重要作用,，科研人員一直希望搞清楚炎癥相關(guān)基因上的SNP位點(diǎn)與罹患卵巢癌風(fēng)險(xiǎn)之間的關(guān)系。
近日,，研究人員鑒定出了27個(gè)參與炎癥反應(yīng)的基因,，并努力想確定這些炎癥基因表達(dá)是否真的與卵巢癌的發(fā)病有聯(lián)系。相關(guān)研究成果發(fā)表在Cancer Research雜志上,。
為了分析SNP位點(diǎn)與患卵巢癌風(fēng)險(xiǎn)之間的相關(guān)性,，實(shí)驗(yàn)開始時(shí)研究人員對(duì)900名卵巢癌患者病例組以及1,000名健康正常對(duì)照婦女組的血清標(biāo)本中檢測(cè)了基因組單核苷酸多態(tài)性（SNP位點(diǎn)）的頻率，基因組單核苷酸多態(tài)性又叫SNP位點(diǎn),。
結(jié)果發(fā)現(xiàn)有5個(gè)基因存在有SNP形式,，這些基因與罹患卵巢癌的風(fēng)險(xiǎn)有著密切聯(lián)系。這些基因中包括編碼IL1A,、AloX5等重要基因,。同時(shí)研究人員發(fā)現(xiàn)：不僅IL1A和AloX5基因與罹患卵巢癌有關(guān)，可遺傳的IL1A和AloX5基因的變種也與卵巢癌發(fā)病有聯(lián)系,。
雖然有些女性攜帶的BRCA1和BRCA2發(fā)生遺傳性基因突變后,，患卵巢癌的風(fēng)險(xiǎn)極大提高，但這一人群僅占所有卵巢癌患者數(shù)量的10%左右,。而IL1A基因變種所導(dǎo)致的卵巢癌患者數(shù)量占卵巢癌患者總數(shù)量的30%,，所以IL1A對(duì)卵巢癌發(fā)病的重要性不得不引起重視。研究人員表示：或許將來,，我們可能利用減少慢性炎癥的發(fā)生來降低癌癥的患病風(fēng)險(xiǎn),。(生物谷 Bioon.com)
doi:10.1158/0008-5472.CAN-11-3512
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Ovarian Cancer Risk Associated with Inherited Inflammation-Related Variants
Kristin L. White1, Joellen M. Schildkraut2, Rachel T. Palmieri3, Edwin S. Iversen4, Andrew Berchuck5, Robert A. Vierkant6, David N. Rider7,et al.
The importance of inflammation pathways to the development of many human cancers prompted us to examine the associations between single-nucleotide polymorphisms (SNPs) in inflammation-related genes and risk of ovarian cancer. In a multi-site case-control study, we genotyped SNPs in a large panel of inflammatory genes in 930 epithelial ovarian cancer cases and 1,037 controls using a custom array and analyzed by logistic regression. SNPs with p<0.10 were evaluated among 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) collaboration. Combined analysis revealed association with SNPs rs17561 and rs4848300 in the interleukin gene IL1A which varied by histologic subtype (heterogeneity p=0.03). For example, IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk. Thus, inherited variation in IL1A and ALOX5 appears to affect ovarian cancer risk which, for IL1A, is limited to rarer subtypes. Given the importance of inflammation in tumorigenesis and growing evidence of subtype-specific features in ovarian cancer, functional investigations will be important to help clarify the importance of inherited variation related to inflammation in ovarian carcinogenesis.
