Population-based study of cancer among carriers of a constitutional structural chromosomal rearrangement.

We measured the occurrence of cancer in an unselected cohort of carriers of constitutional structural rearrangements in virtually complete nationwide registries for cancer and constitutional cytogenetic abnormalities. We identified 4,816 carriers of a constitutional structural rearrangement in the Danish Cytogenetic Registry and searched for cancer diagnoses by linkage to the Danish Cancer Registry. There was no overall increased risk for cancer among carriers (standardized incidence ratio [SIR], 0.96; 95% confidence interval [CI], 0.84-1.10), and no significant difference from that expected was found in balanced and unbalanced rearrangements or in any subtypes of rearrangements. We found significantly lower risks for carriers with rearrangements involving chromosome 21 (SIR, 0.50; 95% CI, 0.22-0.99) and for paternally inherited rearrangements (SIR, 0.30; 95% CI, 0.06-0.88). Risk estimates for the observed type-specific cancers showed an increased risk for non-Hodgkin lymphoma (SIR, 2.11; 95% CI, 1.09-3.69). However, subgroup analyses were not guided by study hypotheses, and our statistical evaluation of the data should be looked upon as exploratory. In addition, we found 12 constitutional structural rearrangements with a breakpoint potentially associated with a cancer-related gene. Potential new loci associated with type-specific cancers were suggested by the findings of families with more than one affected carrier and by the involvement of the same cytogenetic bands in unrelated carriers. Molecular mapping of these breakpoints might provide new insight into cancer predisposition.