Genetically Determined Height and Risk of Non-hodgkin Lymphoma.
Moore A., Kane E., Wang Z., Panagiotou OA., Teras LR., Monnereau A., Wong Doo N., Machiela MJ., Skibola CF., Slager SL., Salles G., Camp NJ., Bracci PM., Nieters A., Vermeulen RCH., Vijai J., Smedby KE., Zhang Y., Vajdic CM., Cozen W., Spinelli JJ., Hjalgrim H., Giles GG., Link BK., Clavel J., Arslan AA., Purdue MP., Tinker LF., Albanes D., Ferri GM., Habermann TM., Adami H-O., Becker N., Benavente Y., Bisanzi S., Boffetta P., Brennan P., Brooks-Wilson AR., Canzian F., Conde L., Cox DG., Curtin K., Foretova L., Gapstur SM., Ghesquières H., Glenn M., Glimelius B., Jackson RD., Lan Q., Liebow M., Maynadie M., McKay J., Melbye M., Miligi L., Milne RL., Molina TJ., Morton LM., North KE., Offit K., Padoan M., Patel AV., Piro S., Ravichandran V., Riboli E., de Sanjose S., Severson RK., Southey MC., Staines A., Stewart C., Travis RC., Weiderpass E., Weinstein S., Zheng T., Chanock SJ., Chatterjee N., Rothman N., Birmann BM., Cerhan JR., Berndt SI.
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, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 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.