Birth order pattern in the inheritance of chronic lymphocytic leukaemia and related lymphoproliferative disease.
Rank order of affected offspring in a sibship can inform on epigenetic factors in disease susceptibility. Here we report an analysis of birth order in 32 families segregating chronic lymphocytic leukaemia (CLL) and other B-cell lymphoproliferative disorders. A paternal-offspring, but not a maternal-offspring birth rank order was observed. Cox regression analysis provided relative risks (RR) for paternal and maternal transmission of 3.60 (CI 95%: 1.54 - 8.42; P = 0.0005) and 1.64 (CI 95%: 0.90 - 3.01; P = 0.096), respectively. The significance of paternal and maternal transmission of CLL-CLL pairs employing Haldane and Smith's test were 0.006 and 0.63, respectively. There was no evidence of a relationship between parental age and birth order. The genetic mechanism behind the birth order effect observed is discussed in the light of non-Mendelian imprinting and pregnancy related microchimerism.
Jønsson
Viggo
V
Haematology Department, Aker University Hospital, University of Oslo, Norway. viggo.jonsson@medisin.uio.no
Tjønnfjord
Geir
G
Samuelsen
Sven Ove
SO
Johannesen
Tom
T
Olsen
Jørgen
J
Sellick
Gabrielle
G
Houlston
Richard
R
Yuille
Martin
M
Catovsky
Daniel
D
D000328:Adult; D000368:Aged; D001722:Birth Order; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis