Hematological malignancies are blood cancers including leukemia, lymphoma and myeloma. One of the striking features of HMs is their propensity to cluster within families indicating that genetic variation is an important risk factor for disease. Given that telomere length has been shown to be heritable in families and genetic variants are known to influence telomere length it is possible that part of the familial risk of HMs occurs through telomere length. Telomere length is a known risk factor for a range of cancers with excessive telomere shortening leading to genetic instability and resulting in the malignant transformation of cells. Increasingly telomere biology is being shown to be important in the development of HMs. To evaluate whether telomeres are shorter in familial HM cases telomere length was measured by quantitative PCR in 54 familial HM cases, 190 unaffected relatives of familial HM cases, 76 non-familial HM cases and compared to telomere length in 758 controls. Variance components modeling of telomere length in SOLAR, taking into account familial relationships, was used to determine factors that contribute to variation in telomere length in the study samples.
Through SOLAR, the heritability of telomere length was calculated to be 64.3% (P=5.5×10−5, SE=0.15) indicating that around 2/3 of the variation in telomere length in these families is influenced by genetics. Additional analysis of telomere length compared across the dataset found that familial cases had significantly shorter telomeres (P=7.4×10−4) whilst non-familial HM cases did not (P=0.74). These data suggest that telomere shortening may be a feature that contributes to the occurrence of familial HMs. Further, the genetic variation within families that influences telomere length may suggest a mechanism for the familial risk of HMs.