Cancer variation associated with the position of the mutation in the BRCA2 gene

Jan Lubinski, Catherine M. Phelan, Parviz Ghadirian, Henry T. Lynch, Judy Garber, Barbara Weber, Nadine Tung, Douglas Horsman, Claudine Isaacs, Alvaro N A Monteiro, Ping Sun, Steven A. Narod

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Abstract

Inherited mutations of the BRCA2 gene give rise to a multi-site cancer phenotype which includes breast cancer (in female and males), ovarian, pancreatic and prostate cancer, ocular and other melanomas, laryngeal, colon and stomach cancers. Interpretation of test results and risk assessment is therefore complex. It has been proposed that families with mutations in the ovarian cancer cluster region (OCCR) of exon 11 (nucleotides 3035-6629) express a higher ratio of ovarian to breast cancer, than families with mutations elsewhere in the BRCA2 gene. In this study we have investigated the presence of 7 types of cancer (ovary, male breast, pancreas, prostate, colon, stomach and melanoma) in first- and second-degree relatives of mutation-positive individuals in 440 families with a BRCA2 mutation. We reviewed histories of cancer in relatives among families with mutations distributed throughout the gene. Families with ovarian cancer were more likely to harbour mutations in the OCCR (nucleotides 3035-6629) than elsewhere in the gene (OR = 2.21; P = 0.0002). We also compared cancer risks according to ethnic group. Ashkenazi Jewish families with the 6174delT founder mutation were more likely to have a family member with ovarian cancer (OR = 1.58; P = 0.002) and less likely to have a family member with prostate cancer (OR = 0.62; P = 0.04) than were non-Jewish families. In contrast, a reduced presence of ovarian cancer was found in families of French-Canadian ancestry, compared to other ancestries (OR = 0.37; P = 0.0026). A high risk of male breast cancer was observed with the 6503delTT mutation (OR = 15.7; P = 0.023). Families of Polish ancestry had a reduced frequency of pancreatic cancer (OR = 0.0; P = 0.03) compared to families of other ethnic origins. In conclusion, both the position of mutation and the ethnic background of the family appear to contribute to the phenotypic variation observed in families with BRCA2 mutations.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalFamilial Cancer
Volume3
Issue number1
DOIs
StatePublished - 2004

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BRCA2 Gene
Mutation
Neoplasms
Ovarian Neoplasms
Male Breast Neoplasms
Pancreatic Neoplasms
Melanoma
Prostatic Neoplasms
Eye Neoplasms
Nucleotides
Laryngeal Neoplasms

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics

Cite this

Lubinski, J., Phelan, C. M., Ghadirian, P., Lynch, H. T., Garber, J., Weber, B., ... Narod, S. A. (2004). Cancer variation associated with the position of the mutation in the BRCA2 gene. Familial Cancer, 3(1), 1-10. https://doi.org/10.1023/B:FAME.0000026816.32400.45

Cancer variation associated with the position of the mutation in the BRCA2 gene. / Lubinski, Jan; Phelan, Catherine M.; Ghadirian, Parviz; Lynch, Henry T.; Garber, Judy; Weber, Barbara; Tung, Nadine; Horsman, Douglas; Isaacs, Claudine; Monteiro, Alvaro N A; Sun, Ping; Narod, Steven A.

In: Familial Cancer, Vol. 3, No. 1, 2004, p. 1-10.

Research output: Contribution to journalArticle

Lubinski, J, Phelan, CM, Ghadirian, P, Lynch, HT, Garber, J, Weber, B, Tung, N, Horsman, D, Isaacs, C, Monteiro, ANA, Sun, P & Narod, SA 2004, 'Cancer variation associated with the position of the mutation in the BRCA2 gene', Familial Cancer, vol. 3, no. 1, pp. 1-10. https://doi.org/10.1023/B:FAME.0000026816.32400.45
Lubinski, Jan ; Phelan, Catherine M. ; Ghadirian, Parviz ; Lynch, Henry T. ; Garber, Judy ; Weber, Barbara ; Tung, Nadine ; Horsman, Douglas ; Isaacs, Claudine ; Monteiro, Alvaro N A ; Sun, Ping ; Narod, Steven A. / Cancer variation associated with the position of the mutation in the BRCA2 gene. In: Familial Cancer. 2004 ; Vol. 3, No. 1. pp. 1-10.
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AU - Ghadirian, Parviz

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AU - Garber, Judy

AU - Weber, Barbara

AU - Tung, Nadine

AU - Horsman, Douglas

AU - Isaacs, Claudine

AU - Monteiro, Alvaro N A

AU - Sun, Ping

AU - Narod, Steven A.

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