Wang Sophia S, Slager Susan L, Brennan Paul, Holly Elizabeth A, De Sanjose Silvia, Bernstein Leslie, Boffetta Paolo, Cerhan James R, Maynadie Marc, Spinelli John J, Chiu Brian C H, Cocco Pier Luigi, Mensah Fiona, Zhang Yawei, Nieters Alexandra, Dal Maso Luigino, Bracci Paige M, Costantini Adele Seniori, Vineis Paolo, Severson Richard K, Roman Eve, Cozen Wendy, Weisenburger Dennis, Davis Scott, Franceschi Silvia, La Vecchia Carlo, Foretova Lenka, Becker Nikolaus, Staines Anthony, Vornanen Martine, Zheng Tongzhang, Hartge Patricia
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Bethesda, MD 20892, USA.
Blood. 2007 Apr 15;109(8):3479-88. doi: 10.1182/blood-2006-06-031948. Epub 2006 Dec 21.
A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.
常见基因变异改变非霍奇金淋巴瘤(NHL)风险的证据不断积累,这支持了遗传易感性在NHL发病中所起的作用。然而,NHL的遗传模式仍知之甚少。我们对国际淋巴瘤流行病学联盟(InterLymph)的10211例NHL病例和11905例对照进行了汇总分析,以评估一级亲属患有造血系统恶性肿瘤者患NHL的风险。通过无条件逻辑回归模型估计NHL及其亚型的比值比(OR)和95%置信区间(CI),并对混杂因素进行校正。报告有患NHL的一级亲属的个体,其患NHL的风险升高(OR = 1.5;95%CI = 1.2 - 1.9),患霍奇金淋巴瘤的风险升高(OR = 1.6;95%CI = 1.1 - 2.3),患白血病的风险升高(OR = 1.4;95%CI = 1.2 - 2.7)。报告有患NHL的兄弟的个体风险最高(OR = 2.8;95%CI = 1.6 - 4.8),且在所评估的所有NHL亚型中风险一致。如果一级亲属患有霍奇金淋巴瘤,若该亲属为父母,则患NHL的风险最高(OR = 1.7;95%CI = 1.0 - 2.9)。如果一级亲属患有白血病,报告有患白血病姐妹的女性患NHL的风险最高(OR = 3.0;95%CI = 1.6 - 5.6)。NHL的遗传模式在各NHL亚型中似乎是一致的,但风险模式因特定的造血系统恶性肿瘤以及亲属的性别而异,这揭示了疾病病因的关键线索。