Risk factors for non-Hodgkin lymphoma subtypes defined by histology and t(14;18) in a population-based case-control study.
The t(14;18) chromosomal translocation is the most common cytogenetic abnormality in non-Hodgkin lymphoma (NHL), occurring in 70-90% of follicular lymphomas (FL) and 30-50% of diffuse large B-cell lymphomas (DLBCL). Previous t(14;18)-NHL studies have not evaluated risk factors for NHL defined by both t(14;18) status and histology. In this population-based case-control study, t(14;18) status was determined in DLBCL cases using fluorescence in situ hybridization on paraffin-embedded tumor sections. Polytomous logistic regression was used to evaluate the association between a wide variety of exposures and t(14;18)-positive (N=109) and -negative DLBCL (N=125) and FL (N=318), adjusting for sex, age, race, and study center. Taller height, more lifetime surgeries, and PCB180 exposure were associated with t(14;18)-positivity. Taller individuals (third tertile vs. first tertile) had elevated risks of t(14;18)-positive DLBCL (odds ratio [OR] = 1.8, 95% confidence interval [CI] 1.1-3.0) and FL (OR=1.4, 95%CI 1.0-1.9) but not t(14;18)-negative DLBCL. Similar patterns were seen for individuals with more lifetime surgeries (13+ vs. 0-12 surgeries; t(14;18)-positive DLBCL OR=1.4, 95%CI 0.7-2.7; FL OR=1.6, 95%CI 1.1-2.5) and individuals exposed to PCB180 greater than 20.8 ng/g (t(14;18)-positive DLBCL OR=1.3, 95%CI 0.6-2.9; FL OR=1.7, 95%CI 1.0-2.8). In contrast, termite treatment and high alpha-chlordane levels were associated with t(14;18)-negative DLBCL only, suggesting that these exposures do not act through t(14;18). Our findings suggest that putative associations between NHL and height, surgeries, and PCB180 may be t(14;18)-mediated and provide support for case-subtyping based on molecular and histologic subtypes. Future efforts should focus on pooling data to confirm and extend previous research on risk factors for t(14;18)-NHL subtypes.
Chang
Cindy M
CM
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD 20892, USA. changcm@mail.nih.gov
Wang
Sophia S
SS
Dave
Bhavana J
BJ
Jain
Smrati
S
Vasef
Mohammad A
MA
Weisenburger
Dennis D
DD
Cozen
Wendy
W
Davis
Scott
S
Severson
Richard K
RK
Lynch
Charles F
CF
Rothman
Nathaniel
N
Cerhan
James R
JR
Hartge
Patricia
P
Morton
Lindsay M
LM
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000145:classification* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D014178:Translocation, Genetic; D014481:United States / Q000453:epidemiology; D055815:Young Adult