2011年，全球估计有225,500名卵巢癌患者新增病例。众所周知慢性炎症会影响多种恶性肿瘤的发生及发展，其中就包括卵巢癌。由于炎症在多种癌症类型中发挥重要作用，科研人员一直希望搞清楚炎症相关基因上的SNP位点与罹患卵巢癌风险之间的关系。
近日，研究人员鉴定出了27个参与炎症反应的基因，并努力想确定这些炎症基因表达是否真的与卵巢癌的发病有联系。相关研究成果发表在Cancer Research杂志上。
为了分析SNP位点与患卵巢癌风险之间的相关性，实验开始时研究人员对900名卵巢癌患者病例组以及1,000名健康正常对照妇女组的血清标本中检测了基因组单核苷酸多态性（SNP位点）的频率，基因组单核苷酸多态性又叫SNP位点。
结果发现有5个基因存在有SNP形式，这些基因与罹患卵巢癌的风险有着密切联系。这些基因中包括编码IL1A、AloX5等重要基因。同时研究人员发现：不仅IL1A和AloX5基因与罹患卵巢癌有关，可遗传的IL1A和AloX5基因的变种也与卵巢癌发病有联系。
虽然有些女性携带的BRCA1和BRCA2发生遗传性基因突变后，患卵巢癌的风险极大提高，但这一人群仅占所有卵巢癌患者数量的10%左右。而IL1A基因变种所导致的卵巢癌患者数量占卵巢癌患者总数量的30%，所以IL1A对卵巢癌发病的重要性不得不引起重视。研究人员表示：或许将来，我们可能利用减少慢性炎症的发生来降低癌症的患病风险。(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.
