Moore Amy, Kane Eleanor, Wang Zhaoming, Panagiotou Orestis A, Teras Lauren R, Monnereau Alain, Wong Doo Nicole, Machiela Mitchell J, Skibola Christine F, Slager Susan L, Salles Gilles, Camp Nicola J, Bracci Paige M, Nieters Alexandra, Vermeulen Roel C H, Vijai Joseph, Smedby Karin E, Zhang Yawei, Vajdic Claire M, Cozen Wendy, Spinelli John J, Hjalgrim Henrik, Giles Graham G, Link Brian K, Clavel Jacqueline, Arslan Alan A, Purdue Mark P, Tinker Lesley F, Albanes Demetrius, Ferri Giovanni M, Habermann Thomas M, Adami Hans-Olov, Becker Nikolaus, Benavente Yolanda, Bisanzi Simonetta, Boffetta Paolo, Brennan Paul, Brooks-Wilson Angela R, Canzian Federico, Conde Lucia, Cox David G, Curtin Karen, Foretova Lenka, Gapstur Susan M, Ghesquières Hervé, Glenn Martha, Glimelius Bengt, Jackson Rebecca D, Lan Qing, Liebow Mark, Maynadie Marc, McKay James, Melbye Mads, Miligi Lucia, Milne Roger L, Molina Thierry J, Morton Lindsay M, North Kari E, Offit Kenneth, Padoan Marina, Patel Alpa V, Piro Sara, Ravichandran Vignesh, Riboli Elio, de Sanjose Silvia, Severson Richard K, Southey Melissa C, Staines Anthony, Stewart Carolyn, Travis Ruth C, Weiderpass Elisabete, Weinstein Stephanie, Zheng Tongzhang, Chanock Stephen J, Chatterjee Nilanjan, Rothman Nathaniel, Birmann Brenda M, Cerhan James R, Berndt Sonja I
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States.
Department of Health Sciences, University of York, York, United Kingdom.
Front Oncol. 2020 Jan 28;9:1539. doi: 10.3389/fonc.2019.01539. eCollection 2019.
Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
尽管证据并不一致，但流行病学研究表明，成年身高较高可能与某些非霍奇金淋巴瘤（NHL）亚型的风险增加有关。身高很大程度上由遗传因素决定，但这些遗传因素如何导致NHL风险尚不清楚。我们使用来自八项全基因组关联研究（GWAS）的数据，调查了身高的遗传决定因素与NHL风险之间的关系，这些研究包括10629例NHL病例，其中有3857例弥漫性大B细胞淋巴瘤（DLBCL）、2847例滤泡性淋巴瘤（FL）、3100例慢性淋巴细胞白血病（CLL）和825例边缘区淋巴瘤（MZL）病例，以及9505例欧洲血统的对照。我们通过使用833个与身高相关的单核苷酸多态性（SNP）构建多基因风险评分来评估遗传预测身高。我们使用逻辑回归估计每个GWAS中遗传决定身高与四种NHL亚型风险之间关联的比值比（OR）和95%置信区间（CI），然后使用固定效应荟萃分析来合并各研究的亚型结果。我们发现遗传决定的较高身高与CLL风险增加之间存在提示性证据（OR = 1.08，95% CI = 1.00 - 1.17，P = 0.049），在女性中这种关联稍强（OR = 1.15，95% CI：1.01 - 1.31，P = 0.036）。未观察到与DLBCL、FL或MZL有显著关联。我们的研究结果表明，CLL和身高之间可能存在一些共同的遗传因素，但其他内源性或环境因素可能是已报道的身高与其他亚型之间流行病学关联的基础。
