The p53 Arg72Pro and Ins16bp polymorphisms and their haplotypes are not associated with breast cancer risk in BRCA-mutation negative familial cases

Giovanna De Vecchi, Paolo Verderio, Sara Pizzamiglio, Siranoush Manoukian, Loris Bernard, Valeria Pensotti, Sara Volorio, Fernando Ravagnani, Paolo Radice, Paolo Peterlongo

Research output: Contribution to journalArticle

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Abstract

Background: Germline disease-causing mutations in BRCA1 and BRCA2 genes confer high risk of breast and ovarian cancer, but account approximately for only 15% of familial cases. Theoretical models and experimental observations have indicated that the remaining familial aggregations would be explained by low-penetrance alleles. Moreover, alleles acting as genetic modifiers would modulate the breast cancer risk in carriers of BRCA mutations. The Ins16bp and Arg72Pro polymorphisms of p53 were implicated in breast cancer and recently it has been shown that these polymorphisms could have an effect when combined as specific haplotypes. Here, we investigated the possible role of the Ins16bp and Arg72Pro polymorphisms and their haplotypes as low-penetrance alleles in familial breast cancer. Methods: The Ins16bp and Arg72Pro polymorphisms were genotyped in a total of 350 familial index cases affected with breast cancer and negative for mutations in BRCA genes, and 352 controls. The Ins16bp and Arg72Pro polymorphisms were studied separately, and as haplotypes and haplotypes combinations. Results: None of the performed analyses resulted statistically significant. Conclusions: These observations suggested that neither the Ins16bp or Arg72Pro polymorphisms considered separately, nor any related haplotype, were associated with breast cancer risk in BRCA-mutation negative familial cases.

Original languageEnglish
Pages (from-to)140-143
Number of pages4
JournalCancer Detection and Prevention
Volume32
Issue number2
DOIs
Publication statusPublished - 2008

Fingerprint

Haplotypes
Breast Neoplasms
Mutation
Penetrance
Alleles
BRCA2 Gene
BRCA1 Gene
Ovarian Neoplasms
Theoretical Models
Genes

Keywords

  • BRCA-mutation negative familial cases
  • Breast cancer susceptibility
  • Ins16bp and Arg72Pro polymorphisms
  • Low-penetrance allele
  • p53 haplotypes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The p53 Arg72Pro and Ins16bp polymorphisms and their haplotypes are not associated with breast cancer risk in BRCA-mutation negative familial cases. / De Vecchi, Giovanna; Verderio, Paolo; Pizzamiglio, Sara; Manoukian, Siranoush; Bernard, Loris; Pensotti, Valeria; Volorio, Sara; Ravagnani, Fernando; Radice, Paolo; Peterlongo, Paolo.

In: Cancer Detection and Prevention, Vol. 32, No. 2, 2008, p. 140-143.

Research output: Contribution to journalArticle

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abstract = "Background: Germline disease-causing mutations in BRCA1 and BRCA2 genes confer high risk of breast and ovarian cancer, but account approximately for only 15{\%} of familial cases. Theoretical models and experimental observations have indicated that the remaining familial aggregations would be explained by low-penetrance alleles. Moreover, alleles acting as genetic modifiers would modulate the breast cancer risk in carriers of BRCA mutations. The Ins16bp and Arg72Pro polymorphisms of p53 were implicated in breast cancer and recently it has been shown that these polymorphisms could have an effect when combined as specific haplotypes. Here, we investigated the possible role of the Ins16bp and Arg72Pro polymorphisms and their haplotypes as low-penetrance alleles in familial breast cancer. Methods: The Ins16bp and Arg72Pro polymorphisms were genotyped in a total of 350 familial index cases affected with breast cancer and negative for mutations in BRCA genes, and 352 controls. The Ins16bp and Arg72Pro polymorphisms were studied separately, and as haplotypes and haplotypes combinations. Results: None of the performed analyses resulted statistically significant. Conclusions: These observations suggested that neither the Ins16bp or Arg72Pro polymorphisms considered separately, nor any related haplotype, were associated with breast cancer risk in BRCA-mutation negative familial cases.",
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T1 - The p53 Arg72Pro and Ins16bp polymorphisms and their haplotypes are not associated with breast cancer risk in BRCA-mutation negative familial cases

AU - De Vecchi, Giovanna

AU - Verderio, Paolo

AU - Pizzamiglio, Sara

AU - Manoukian, Siranoush

AU - Bernard, Loris

AU - Pensotti, Valeria

AU - Volorio, Sara

AU - Ravagnani, Fernando

AU - Radice, Paolo

AU - Peterlongo, Paolo

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AB - Background: Germline disease-causing mutations in BRCA1 and BRCA2 genes confer high risk of breast and ovarian cancer, but account approximately for only 15% of familial cases. Theoretical models and experimental observations have indicated that the remaining familial aggregations would be explained by low-penetrance alleles. Moreover, alleles acting as genetic modifiers would modulate the breast cancer risk in carriers of BRCA mutations. The Ins16bp and Arg72Pro polymorphisms of p53 were implicated in breast cancer and recently it has been shown that these polymorphisms could have an effect when combined as specific haplotypes. Here, we investigated the possible role of the Ins16bp and Arg72Pro polymorphisms and their haplotypes as low-penetrance alleles in familial breast cancer. Methods: The Ins16bp and Arg72Pro polymorphisms were genotyped in a total of 350 familial index cases affected with breast cancer and negative for mutations in BRCA genes, and 352 controls. The Ins16bp and Arg72Pro polymorphisms were studied separately, and as haplotypes and haplotypes combinations. Results: None of the performed analyses resulted statistically significant. Conclusions: These observations suggested that neither the Ins16bp or Arg72Pro polymorphisms considered separately, nor any related haplotype, were associated with breast cancer risk in BRCA-mutation negative familial cases.

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