Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study.
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Date
2019-09-15Author
Schoemaker, MJ
Jones, ME
Higgins, CD
Wright, AF
UK Clinical Cytogenetics Group,
Swerdlow, AJ
Type
Journal Article
Metadata
Show full item recordAbstract
The constitutional t(11;22)(q23;q11) translocation is the only recurrent non-Robertsonian translocation known in humans. Carriers are phenotypically normal and are usually referred for cytogenetic testing because of multiple miscarriages, infertility, or having aneuploidy in offspring. A breast cancer predisposition has been suggested, but previous studies have been small and had methodological shortcomings. We therefore conducted a long-term prospective study of cancer and mortality risk in carriers. We followed 65 male and 101 female carriers of t(11;22)(q23;q11) diagnosed in cytogenetic laboratories in Britain during 1976-2005 for cancer and deaths for an average of 21.4 years per subject. Standardised mortality (SMR) and incidence (SIR) ratios were calculated comparing the numbers of observed events with those expected from national age-, sex-, country- and calendar-period-specific population rates. Cancer incidence was borderline significantly raised for cancer overall (SIR = 1.56, 95% CI: 0.98-2.36, n = 22), and significantly raised for invasive breast cancer (SIR = 2.74, 95% CI: 1.18-5.40, n = 8) and in situ breast cancer (SIR = 13.0, 95% CI: 3.55-33.4, n = 4). Breast cancer risks were particularly increased at ages <50 (SIR = 4.37, 95% CI: 1.42-10.2 for invasive, SIR = 22.8, 95% CI: 2.76-82.5 for in situ). Mortality was borderline significantly raised for breast cancer (SMR = 4.82, 95% CI: 0.99-14.1) but not significantly raised for other cancers or causes. Individuals diagnosed with t(11;22)(q23;q11) appear to be at several-fold increased breast cancer risk, with the greatest risks at premenopausal ages. Further research is required to understand the genetic mechanism involving 11q23 and 22q11 and there may be a need for enhanced breast cancer surveillance among female carriers.
Collections
Subject
UK Clinical Cytogenetics Group
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 22
Humans
Neoplasms
Translocation, Genetic
Genetic Predisposition to Disease
Incidence
Prospective Studies
Heterozygote
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Child
Child, Preschool
Infant
Infant, Newborn
Male
Young Adult
United Kingdom
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2018-11-13
License start date
2019-09
Citation
International journal of cancer, 2019, 145 (6), pp. 1493 - 1498
Publisher
WILEY