Risk of breast cancer not increased in translocation 11;22 carriers: Analysis of 80 pedigrees

Carter, Melissa T.; Barrowman, Nicholas J.; Pierre, Stephanie A. St.; Emanuel, Beverly S.; Boycott, Kym M.

doi:10.1002/ajmg.a.33166

Cited by 5 publications

(6 citation statements)

References 15 publications

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“…Although carriers of the balanced t(11;22)(q23;q11) are generally phenotypically normal, we note that there are reports of increased cancer incidence in these carriers (Lindblom et al 1994;Jobanputra et al 2005;Wieland et al 2006;Carter et al 2010), and speculate that the altered gene expression we observe may underlie this. Furthermore, our observations raise the possibility that translocations in cancer cells may contribute to oncogenesis not only by disrupting the gene, or genes mapping around the breakpoints, but also through changes in expression of genes positioned elsewhere on the affected chromosomes and on other displaced chromosomes, a hypothesis that warrants detailed investigation in the future.…”

Section: Differentially Expressed Genes Show Position Changes Within mentioning

confidence: 44%

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The effect of translocation-induced nuclear reorganization on gene expression

Harewood¹,

Schütz²,

Boyle³

et al. 2010

Genome Res.

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Translocations are known to affect the expression of genes at the breakpoints and, in the case of unbalanced translocations, alter the gene copy number. However, a comprehensive understanding of the functional impact of this class of variation is lacking. Here, we have studied the effect of balanced chromosomal rearrangements on gene expression by comparing the transcriptomes of cell lines from controls and individuals with the t(11;22)(q23;q11) translocation. The number of differentially expressed transcripts between translocation-carrying and control cohorts is significantly higher than that observed between control samples alone, suggesting that balanced rearrangements have a greater effect on gene expression than normal variation. Many of the affected genes are located along the length of the derived chromosome 11. We show that this chromosome is concomitantly altered in its spatial organization, occupying a more central position in the nucleus than its nonrearranged counterpart. Derivative 22-mapping chromosome 22 genes, on the other hand, remain in their usual environment. Our results are consistent with recent studies that experimentally altered nuclear organization, and indicated that nuclear position plays a functional role in regulating the expression of some genes in mammalian cells. Our study suggests that chromosomal translocations can result in hitherto unforeseen, large-scale changes in gene expression that are the consequence of alterations in normal chromosome territory positioning. This has consequences for the patterns of gene expression change seen during tumorigenesis-associated genome instability and during the karyotype changes that lead to speciation.

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Section: Differentially Expressed Genes Show Position Changes Within mentioning

confidence: 44%

“…comm.). Carriers of the translocation are phenotypically normal, although some studies have shown they have up to a 10-fold greater risk of developing breast cancer than cytogenetically normal individuals (Lindblom et al 1994;Jobanputra et al 2005;Wieland et al 2006;Carter et al 2010). Carriers are also at risk of having progeny with Emanuel syndrome (OMIM no.…”

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confidence: 99%

The effect of translocation-induced nuclear reorganization on gene expression

Harewood¹,

Schütz²,

Boyle³

et al. 2010

Genome Res.

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“…Previous reports of a breast cancer predisposition in t(11;22) carriers have been based on identification of individuals with a history of breast cancer in pedigree studies or case series of carriers . Some of the studies have had contradictory results, however.…”

Section: Discussionmentioning

confidence: 99%

“…Lindblom et al observed four cases of breast cancer among 16 female carriers identified from eight pedigree families, which they estimated constituted a 10‐fold increased risk . However, the largest pedigree study to date, by Carter et al , did not observe an excess of breast cancer cases among 103 female carriers from 80 pedigrees ascertained for reproductive‐related reasons . Information on carrier status and breast cancer in relatives was initially obtained from a proband carrier in each family and such dependence on recall by the proband is a possible cause of bias.…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of mortality and cancer risks in t(11;22) carriers is important for counselling of carriers and can additionally provide insights into our understanding of cancer aetiology. A predisposition to breast cancer among female carriers has been suggested based on the presence of subjects with a history of breast cancer among relatively small clinical series of carriers, although a recent pedigree study did not observe an excess of cases . Such studies have several potential methodological shortcomings including biased selection of carriers, dependence on recall of historical breast cancer diagnoses in relatives by a proband, and lack of detail on relatives to compute the expected numbers of cases.…”

Section: Introductionmentioning

confidence: 99%

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Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study

Schoemaker

Jones

Higgins

et al. 2019

Intl Journal of Cancer

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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.

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