Inherited Breast Cancer in Nigerian Women.
Inherited Breast Cancer in Nigerian Women.
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DOI：
10.1200/jco.2018.78.3977
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发表时间：
2018-10-01
期刊：
影响因子：
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通讯作者：
Olopade OI
中科院分区：
文献类型：
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作者：
Zheng Y;Walsh T;Gulsuner S;Casadei S;Lee MK;Ogundiran TO;Ademola A;Falusi AG;Adebamowo CA;Oluwasola AO;Adeoye A;Odetunde A;Babalola CP;Ojengbede OA;Odedina S;Anetor I;Wang S;Huo D;Yoshimatsu TF;Zhang J;Felix GES;King MC;Olopade OI
在尼日利亚妇女中，乳腺癌是在晚期被诊断出来的，更常见的是三阴性疾病，并且比欧洲或美国更常见的致命性。我们评估了这一人群中遗传易感性对乳腺癌的贡献。病例为尼日利亚伊巴丹确诊的1，136例浸润性乳腺癌妇女（诊断时平均年龄为47.5 ± 11.5岁）。患者的选择不考虑诊断时的年龄，家族史或先前的基因检测。对照组为来自同一社区的997名未患癌症的妇女（平均年龄为47.0 ± 12.4岁）。使用BROCA面板测序来鉴定已知和候选乳腺癌基因中的功能丧失突变。在577例有肿瘤分期信息的患者中，86.1%（497例）被诊断为III期（241例）或IV期（256例）。在290例有肿瘤激素受体状态和人表皮生长因子受体2信息的患者中，45.9%（133例）患有三阴性乳腺癌。在所有病例中，14.7%（1，136例中的167例）携带乳腺癌基因功能丧失突变：BRCA 1为7.0%，BRCA 2为4.1%，PALB 2为1.0%，TP 53为0.4%，其他10个基因中的任何一个均为2.1%。BRCA 1和BRCA 2的比值比分别为23.4（95% CI，7.4 - 73.9）和10.3（95% CI，3.7 - 28.5）。风险也与PALB 2（11例，零对照; P = 0.002）和TP 53（5例，零对照; P = 0.036）显著相关。与其他患者相比，BRCA 1突变携带者更年轻（P <0.001），更容易患三阴性乳腺癌（P = 0.028）。在尼日利亚妇女中，八分之一的浸润性乳腺癌病例是BRCA 1、BRCA 2、PALB 2或TP 53遗传突变的结果，与这些基因相关的乳腺癌风险极高。鉴于资源有限，预防和早期发现服务应特别侧重于这些风险最高的妇女。
Among Nigerian women, breast cancer is diagnosed at later stages, is more frequently triple-negative disease, and is far more frequently fatal than in Europe or the United States. We evaluated the contribution of an inherited predisposition to breast cancer in this population. Cases were 1,136 women with invasive breast cancer (mean age at diagnosis, 47.5 ± 11.5 years) ascertained in Ibadan, Nigeria. Patients were selected regardless of age at diagnosis, family history, or prior genetic testing. Controls were 997 women without cancer (mean age at interview, 47.0 ± 12.4 years) from the same communities. BROCA panel sequencing was used to identify loss-of-function mutations in known and candidate breast cancer genes. Of 577 patients with information on tumor stage, 86.1% (497) were diagnosed at stage III (241) or IV (256). Of 290 patients with information on tumor hormone receptor status and human epidermal growth factor receptor 2, 45.9% (133) had triple-negative breast cancer. Among all cases, 14.7% (167 of 1,136) carried a loss-of-function mutation in a breast cancer gene: 7.0% in BRCA1, 4.1% in BRCA2, 1.0% in PALB2, 0.4% in TP53, and 2.1% in any of 10 other genes. Odds ratios were 23.4 (95% CI, 7.4 to 73.9) for BRCA1 and 10.3 (95% CI, 3.7 to 28.5) for BRCA2. Risks were also significantly associated with PALB2 (11 cases, zero controls; P = .002) and TP53 (five cases, zero controls; P = .036). Compared with other patients, BRCA1 mutation carriers were younger (P < .001) and more likely to have triple-negative breast cancer (P = .028). Among Nigerian women, one in eight cases of invasive breast cancer is a result of inherited mutations in BRCA1, BRCA2, PALB2, or TP53, and breast cancer risks associated with these genes are extremely high. Given limited resources, prevention and early detection services should be especially focused on these highest-risk women.