Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis

被引:21
作者
Gannon, Philippe O. [1 ]
Medelci, Sanae [1 ]
Le Page, Cecile [1 ]
Beaulieu, Martin [2 ]
Provencher, Diane M. [1 ,3 ,4 ]
Mes-Masson, Anne-Marie [1 ,4 ]
Santos, Manuela M. [1 ,4 ]
机构
[1] Univ Montreal, Inst Canc Montreal, CRCHUM, Montreal, PQ H2L 4M1, Canada
[2] CHUM, Hop St Luc, Dept Biochim, Montreal, PQ, Canada
[3] Univ Montreal, CHUM, Hop Notre Dame, Dept Gynecol & Obstet, Montreal, PQ, Canada
[4] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
基金
加拿大健康研究院;
关键词
ovarian cancer; HFE mutations; hemochromatosis; iron; prognosis; TRANSFERRIN RECEPTOR; HEREDITARY HEMOCHROMATOSIS; H63D MUTATIONS; IRON-OVERLOAD; PROTEIN HFE; T-CELLS; BREAST; C282Y; BETA(2)-MICROGLOBULIN; ASSOCIATION;
D O I
10.1002/ijc.25577
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer cells require large amounts of micronutrients, particularly iron, for their rapid growth and frequent divisions. Cellular iron uptake is regulated by the transferrin receptor and the hemochromatosis protein (HFE) system. Two frequent mutations in the HFE gene, H63D and C282Y, are associated with hemochromatosis type I, an inherited iron overload disease and, possibly, with cancer. In this study, we evaluated the frequency of the H63D and C282Y mutations in a cohort of 677 consecutive cases of woman with gynecological pathologies. Cases included 80 women with tumor-free pathologies normal ovary (NOV), 124 with benign ovarian tumors (BOV), 96 with epithelial ovarian cancer (EOC) tumors of low malignant potential (LPM), 264 with invasive tumors of the ovary (TOV) and 113 with endometrial cancer. We found that the C282Y allele frequency in EOC patients was higher than that in the control NOV group (5.8% vs. 1.3%, p < 0.001) and was associated with an increased risk of ovarian cancer (OR = 4.88; 95% CI 1.15-20.61; p = 0.018). The effect of the two HFE mutations on patient survival was also analyzed. Kaplan-Meier analyses did not find any significant association between the H63D allele and patient survival. However, EOC patients with at least one C282Y allele had a decreased overall survival compared to those with no C282Y allele (p = 0.001). These results indicate that the C282Y mutation may increase the risk of developing ovarian cancer and may be further associated with poor outcomes.
引用
收藏
页码:2326 / 2334
页数:9
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