Abstract
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.
Highlights
Taller adult height has been associated with an increased risk of several subtypes of non-Hodgkin lymphoma (NHL) [1]; the results have not been consistent across studies for common subtypes, such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small cell lymphoma (CLL)
We found suggestive evidence for an association between taller genetically determined height and risk of CLL (OR = 1.08, 95% confidence intervals (CI) 1.00–1.17, p = 0.049), with the polygenic risk scores (PRS) modeled as a continuous variable (Table 1)
No association was observed between genetically predicted height and the risk of DLBCL (OR = 1.05, 95% CI 0.97–1.14), FL (OR = 1.06, 95% CI 0.97–1.16), or marginal zone lymphoma (MZL) (OR = 1.10, 95% CI 0.95–1.28) (Table 1)
Summary
Taller adult height has been associated with an increased risk of several subtypes of non-Hodgkin lymphoma (NHL) [1]; the results have not been consistent across studies for common subtypes, such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small cell lymphoma (CLL)(2–13). Taller adult height has been associated with an increased risk of several subtypes of non-Hodgkin lymphoma (NHL) [1]; the results have not been consistent across studies for common subtypes, such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small cell lymphoma (CLL). Taller height has been positively associated with other cancers in both epidemiologic and Mendelian randomization studies [14,15,16]. The reported positive associations between height and multiple subtypes of NHL suggest the existence of common biological pathways, possibly mediated by genetic factors. A deeper understanding of how height is associated with NHL risk may provide insight into underlying biological mechanisms leading to lymphoma
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have