CAG repeat size in Huntingtin alleles is associated with cancer prognosis

GEMO

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The abnormal expansion of a ≥36 CAG unit tract in the Huntingtin gene (HTT) leads to Huntington's disease (HD), but has also been associated with cancer: the incidence of cancer is lower in HD patients than in age-matched controls, but HD-causing variants of HTT accelerate the progression of breast tumors and the development of metastases in mouse models of breast cancer. To investigate the relationship between HTT CAGs and cancer, data concerning 2407 women with BRCA1 or BRCA2 mutations that predispose to breast and ovarian cancers and 431 patients with breast cancer without family histories were studied; the size of the CAG expansions on both HTT alleles was determined in each subject. The proportion of individuals carrying a CAG expansion in a pathological range for HD was 10 times more frequent than previously reported in the literature. In carriers of BRCA2 mutations, the length of the HTT CAG tract was correlated with lower incidence of ovarian cancer. Among carriers of BRCA1 mutations who developed a breast cancer, its onset occurred 2.4 years earlier in individuals with intermediate HTT alleles (≥27) than in those with a CAG tract <27. Finally, in patients with sporadic HER2 breast cancer, metastasis increased by a factor of 11.10 per 10 additional CAG repeats in HTT. We concluded that whereas long CAG length could be associated with lower cancer incidence, it could also be paradoxically associated with cancer severity (age of apparition and metastasis development).

Original languageEnglish (US)
Pages (from-to)1310-1315
Number of pages6
JournalEuropean Journal of Human Genetics
Volume24
Issue number9
DOIs
StatePublished - Aug 1 2016

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Alleles
Huntington Disease
Breast Neoplasms
Genes
Neoplasms
Neoplasm Metastasis
Ovarian Neoplasms
Mutation
Incidence
Neoplasm Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

CAG repeat size in Huntingtin alleles is associated with cancer prognosis. / GEMO.

In: European Journal of Human Genetics, Vol. 24, No. 9, 01.08.2016, p. 1310-1315.

Research output: Contribution to journalArticle

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abstract = "The abnormal expansion of a ≥36 CAG unit tract in the Huntingtin gene (HTT) leads to Huntington's disease (HD), but has also been associated with cancer: the incidence of cancer is lower in HD patients than in age-matched controls, but HD-causing variants of HTT accelerate the progression of breast tumors and the development of metastases in mouse models of breast cancer. To investigate the relationship between HTT CAGs and cancer, data concerning 2407 women with BRCA1 or BRCA2 mutations that predispose to breast and ovarian cancers and 431 patients with breast cancer without family histories were studied; the size of the CAG expansions on both HTT alleles was determined in each subject. The proportion of individuals carrying a CAG expansion in a pathological range for HD was 10 times more frequent than previously reported in the literature. In carriers of BRCA2 mutations, the length of the HTT CAG tract was correlated with lower incidence of ovarian cancer. Among carriers of BRCA1 mutations who developed a breast cancer, its onset occurred 2.4 years earlier in individuals with intermediate HTT alleles (≥27) than in those with a CAG tract <27. Finally, in patients with sporadic HER2 breast cancer, metastasis increased by a factor of 11.10 per 10 additional CAG repeats in HTT. We concluded that whereas long CAG length could be associated with lower cancer incidence, it could also be paradoxically associated with cancer severity (age of apparition and metastasis development).",
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AU - Tézenas Du Montcel, Sophie

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AU - Vacher, Sophie

AU - Barjhoux, Laure

AU - Sornin, Valérie

AU - Cazeneuve, Cécile

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AU - Bressac-De-Paillerets, Brigitte

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AU - Bignon, Yves Jean

AU - Uhrhammer, Nancy

AU - Lasset, Christine

AU - Bonadona, Valérie

AU - Handallou, Sandrine

AU - Hardouin, Agnès

AU - Berthet, Pascaline

AU - Sobol, Hagay

AU - Bourdon, Violaine

AU - Noguchi, Tetsuro

AU - Remenieras, Audrey

AU - Eisinger, François

AU - Coupier, Isabelle

AU - Pujol, Pascal

AU - Peyrat, Jean Philippe

AU - Fournier, Joëlle

AU - Révillion, Françoise

AU - Vennin, Philippe

AU - Adenis, Claude

AU - Lynch, Henry T.

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N2 - The abnormal expansion of a ≥36 CAG unit tract in the Huntingtin gene (HTT) leads to Huntington's disease (HD), but has also been associated with cancer: the incidence of cancer is lower in HD patients than in age-matched controls, but HD-causing variants of HTT accelerate the progression of breast tumors and the development of metastases in mouse models of breast cancer. To investigate the relationship between HTT CAGs and cancer, data concerning 2407 women with BRCA1 or BRCA2 mutations that predispose to breast and ovarian cancers and 431 patients with breast cancer without family histories were studied; the size of the CAG expansions on both HTT alleles was determined in each subject. The proportion of individuals carrying a CAG expansion in a pathological range for HD was 10 times more frequent than previously reported in the literature. In carriers of BRCA2 mutations, the length of the HTT CAG tract was correlated with lower incidence of ovarian cancer. Among carriers of BRCA1 mutations who developed a breast cancer, its onset occurred 2.4 years earlier in individuals with intermediate HTT alleles (≥27) than in those with a CAG tract <27. Finally, in patients with sporadic HER2 breast cancer, metastasis increased by a factor of 11.10 per 10 additional CAG repeats in HTT. We concluded that whereas long CAG length could be associated with lower cancer incidence, it could also be paradoxically associated with cancer severity (age of apparition and metastasis development).

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