BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition

Pia Vahteristo (Corresponding Author), Kirsi Syrjäkoski, Tuomas Heikkinen, Hannaleena Eerola, Kristiina Aittomäki, Karl von Smitten, Kaija Holli, Carl Blomqvist, Olli Kallioniemi, Heli Nevanlinna

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Abstract

BARD1 (BRCA1-associated RING-domain 1) is a tumor suppressor whose protein product interacts with BRCA1, and in which rare somatic and germline mutations have been reported in breast, uterine, and endometrial cancers. We aimed to evaluate whether there are BARD1 genetic variants that contribute to breast cancer risk by screening the gene for germline alterations in 45 Finnish familial breast cancer patients and in seven patients with both breast and ovarian cancer. Two of the missense alterations identified (Cys557Ser and Val507Met) were recently suggested to associate with an increased breast cancer risk. We also analyzed these variants in large and independent series of familial and unselected breast cancer patients and healthy controls. No clearly deleterious mutations were detected in the initial mutation screening. No association of the Cys557Ser and breast cancer risk was observed as the variant was found altogether in 1.4% (16/1181) of familial and 2.2% (34/1565) of unselected breast cancer patients, and in 2.5% (27/1083) of healthy controls. The frequency of the Val-allele of the Val507Met variant was modestly higher among breast cancer patients than among healthy controls, although the difference did not reach statistical significance. No statistically significant association of the Cys557Ser or Val507Met variants with any clinicopathologic parameters was observed. These results suggest that the contribution of the BARD1 germline variants to breast cancer predisposition is very limited, and that neither Cys557Ser nor Val507Met have an effect on familial breast cancer susceptibility.
Original languageEnglish
Pages (from-to)167-172
Number of pages6
JournalEuropean Journal of Human Genetics
Volume14
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fingerprint

Breast Neoplasms
Tumor Suppressor Proteins
Uterine Neoplasms
Mutation
Germ-Line Mutation
Endometrial Neoplasms
Early Detection of Cancer
Gene Frequency
Ovarian Neoplasms
Genes
Familial Breast Cancer

Keywords

  • BARD1
  • BRCA1 interacting protein
  • breast cancer risk
  • germline mutation

Cite this

Vahteristo, P., Syrjäkoski, K., Heikkinen, T., Eerola, H., Aittomäki, K., von Smitten, K., ... Nevanlinna, H. (2006). BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition. European Journal of Human Genetics, 14, 167-172. https://doi.org/10.1038/sj.ejhg.5201542
Vahteristo, Pia ; Syrjäkoski, Kirsi ; Heikkinen, Tuomas ; Eerola, Hannaleena ; Aittomäki, Kristiina ; von Smitten, Karl ; Holli, Kaija ; Blomqvist, Carl ; Kallioniemi, Olli ; Nevanlinna, Heli. / BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition. In: European Journal of Human Genetics. 2006 ; Vol. 14. pp. 167-172.
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title = "BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition",
abstract = "BARD1 (BRCA1-associated RING-domain 1) is a tumor suppressor whose protein product interacts with BRCA1, and in which rare somatic and germline mutations have been reported in breast, uterine, and endometrial cancers. We aimed to evaluate whether there are BARD1 genetic variants that contribute to breast cancer risk by screening the gene for germline alterations in 45 Finnish familial breast cancer patients and in seven patients with both breast and ovarian cancer. Two of the missense alterations identified (Cys557Ser and Val507Met) were recently suggested to associate with an increased breast cancer risk. We also analyzed these variants in large and independent series of familial and unselected breast cancer patients and healthy controls. No clearly deleterious mutations were detected in the initial mutation screening. No association of the Cys557Ser and breast cancer risk was observed as the variant was found altogether in 1.4{\%} (16/1181) of familial and 2.2{\%} (34/1565) of unselected breast cancer patients, and in 2.5{\%} (27/1083) of healthy controls. The frequency of the Val-allele of the Val507Met variant was modestly higher among breast cancer patients than among healthy controls, although the difference did not reach statistical significance. No statistically significant association of the Cys557Ser or Val507Met variants with any clinicopathologic parameters was observed. These results suggest that the contribution of the BARD1 germline variants to breast cancer predisposition is very limited, and that neither Cys557Ser nor Val507Met have an effect on familial breast cancer susceptibility.",
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author = "Pia Vahteristo and Kirsi Syrj{\"a}koski and Tuomas Heikkinen and Hannaleena Eerola and Kristiina Aittom{\"a}ki and {von Smitten}, Karl and Kaija Holli and Carl Blomqvist and Olli Kallioniemi and Heli Nevanlinna",
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Vahteristo, P, Syrjäkoski, K, Heikkinen, T, Eerola, H, Aittomäki, K, von Smitten, K, Holli, K, Blomqvist, C, Kallioniemi, O & Nevanlinna, H 2006, 'BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition', European Journal of Human Genetics, vol. 14, pp. 167-172. https://doi.org/10.1038/sj.ejhg.5201542

BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition. / Vahteristo, Pia (Corresponding Author); Syrjäkoski, Kirsi; Heikkinen, Tuomas; Eerola, Hannaleena; Aittomäki, Kristiina; von Smitten, Karl; Holli, Kaija; Blomqvist, Carl; Kallioniemi, Olli; Nevanlinna, Heli.

In: European Journal of Human Genetics, Vol. 14, 2006, p. 167-172.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition

AU - Vahteristo, Pia

AU - Syrjäkoski, Kirsi

AU - Heikkinen, Tuomas

AU - Eerola, Hannaleena

AU - Aittomäki, Kristiina

AU - von Smitten, Karl

AU - Holli, Kaija

AU - Blomqvist, Carl

AU - Kallioniemi, Olli

AU - Nevanlinna, Heli

PY - 2006

Y1 - 2006

N2 - BARD1 (BRCA1-associated RING-domain 1) is a tumor suppressor whose protein product interacts with BRCA1, and in which rare somatic and germline mutations have been reported in breast, uterine, and endometrial cancers. We aimed to evaluate whether there are BARD1 genetic variants that contribute to breast cancer risk by screening the gene for germline alterations in 45 Finnish familial breast cancer patients and in seven patients with both breast and ovarian cancer. Two of the missense alterations identified (Cys557Ser and Val507Met) were recently suggested to associate with an increased breast cancer risk. We also analyzed these variants in large and independent series of familial and unselected breast cancer patients and healthy controls. No clearly deleterious mutations were detected in the initial mutation screening. No association of the Cys557Ser and breast cancer risk was observed as the variant was found altogether in 1.4% (16/1181) of familial and 2.2% (34/1565) of unselected breast cancer patients, and in 2.5% (27/1083) of healthy controls. The frequency of the Val-allele of the Val507Met variant was modestly higher among breast cancer patients than among healthy controls, although the difference did not reach statistical significance. No statistically significant association of the Cys557Ser or Val507Met variants with any clinicopathologic parameters was observed. These results suggest that the contribution of the BARD1 germline variants to breast cancer predisposition is very limited, and that neither Cys557Ser nor Val507Met have an effect on familial breast cancer susceptibility.

AB - BARD1 (BRCA1-associated RING-domain 1) is a tumor suppressor whose protein product interacts with BRCA1, and in which rare somatic and germline mutations have been reported in breast, uterine, and endometrial cancers. We aimed to evaluate whether there are BARD1 genetic variants that contribute to breast cancer risk by screening the gene for germline alterations in 45 Finnish familial breast cancer patients and in seven patients with both breast and ovarian cancer. Two of the missense alterations identified (Cys557Ser and Val507Met) were recently suggested to associate with an increased breast cancer risk. We also analyzed these variants in large and independent series of familial and unselected breast cancer patients and healthy controls. No clearly deleterious mutations were detected in the initial mutation screening. No association of the Cys557Ser and breast cancer risk was observed as the variant was found altogether in 1.4% (16/1181) of familial and 2.2% (34/1565) of unselected breast cancer patients, and in 2.5% (27/1083) of healthy controls. The frequency of the Val-allele of the Val507Met variant was modestly higher among breast cancer patients than among healthy controls, although the difference did not reach statistical significance. No statistically significant association of the Cys557Ser or Val507Met variants with any clinicopathologic parameters was observed. These results suggest that the contribution of the BARD1 germline variants to breast cancer predisposition is very limited, and that neither Cys557Ser nor Val507Met have an effect on familial breast cancer susceptibility.

KW - BARD1

KW - BRCA1 interacting protein

KW - breast cancer risk

KW - germline mutation

U2 - 10.1038/sj.ejhg.5201542

DO - 10.1038/sj.ejhg.5201542

M3 - Article

VL - 14

SP - 167

EP - 172

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -

Vahteristo P, Syrjäkoski K, Heikkinen T, Eerola H, Aittomäki K, von Smitten K et al. BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition. European Journal of Human Genetics. 2006;14:167-172. https://doi.org/10.1038/sj.ejhg.5201542