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 language | English |
|---|---|
| Pages (from-to) | 140-143 |
| Number of pages | 4 |
| Journal | Cancer Detection and Prevention |
| Volume | 32 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2008 |
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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 journal › Article
}
TY - JOUR
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
PY - 2008
Y1 - 2008
N2 - 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.
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.
KW - BRCA-mutation negative familial cases
KW - Breast cancer susceptibility
KW - Ins16bp and Arg72Pro polymorphisms
KW - Low-penetrance allele
KW - p53 haplotypes
UR - http://www.scopus.com/inward/record.url?scp=47749137322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47749137322&partnerID=8YFLogxK
U2 - 10.1016/j.cdp.2008.06.003
DO - 10.1016/j.cdp.2008.06.003
M3 - Article
VL - 32
SP - 140
EP - 143
JO - Cancer Detection and Prevention
JF - Cancer Detection and Prevention
SN - 0361-090X
IS - 2
ER -