RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers

Boning Gao, Xian Jin Xie, Chunxian Huang, David S. Shames, Tina T L Chen, Cheryl M. Lewis, Aihua Bian, Bifeng Zhang, Olufunmilayo I. Olopade, Judy E. Garber, David M. Euhus, Gail E. Tomlinson, John D. Minna

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Abstract

The tumor suppressor gene RASSF1A regulates cell cycle progression, apoptosis, and microtubule stability and is inactivated by promoter methylation in ∼50% of breast cancers. It has been shown previously that the polymorphism A133S in RASSF1A reduces its ability to regulate cell cycle progression and this polymorphism is associated with an increased risk of breast cancer. We analyzed the frequency of RASSF1A A133S in 190 Caucasian women without breast cancer and 653 patients with breast cancer including 138 BRCA1 and BRCA2 (BRCA1/2) mutation carriers, 395 non-BRCA1/2 mutations carriers, and 120 untested for BRCA1/2 mutations. Patients with breast cancer had a higher frequency of A133S than the controls [P = 0.017; odds ratios (OR), 1.71; 95% confidence intervals (95% CI), 1.10-2.66]. There is also a higher frequency of A133S in patients with higher familial breast cancer risk (P = 0.029; OR, 1.76; 95% CI, 1.06-2.92) and patients carrying BRCA1/2 mutations (P = 0.037, OR, 1.82; 95% CI, 1.04-3.18). Importantly, we found that the co-occurrence of a BRCA1 or BRCA2 mutation and A133S in RASSF1A was associated with earlier onset of breast cancer compared with those individuals with either a BRCA1/2 mutation or the A133S polymorphism alone (36.0 versus 42.0 years old, P = 0.002). Our data suggest that the presence of the RASSF1A A133S polymorphism is associated with breast cancer pathogenesis in general and modifies breast cancer age of onset in BRCA1/2 mutations carriers. Our results warrant a large-scale study to examine the effect of the A133S polymorphism in the development of breast and other types of cancers.

Original languageEnglish (US)
Pages (from-to)22-25
Number of pages4
JournalCancer Research
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2008

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Breast Neoplasms
Mutation
Odds Ratio
Confidence Intervals
Cell Cycle
Tumor Suppressor Genes
Age of Onset
Microtubules
Methylation
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers. / Gao, Boning; Xie, Xian Jin; Huang, Chunxian; Shames, David S.; Chen, Tina T L; Lewis, Cheryl M.; Bian, Aihua; Zhang, Bifeng; Olopade, Olufunmilayo I.; Garber, Judy E.; Euhus, David M.; Tomlinson, Gail E.; Minna, John D.

In: Cancer Research, Vol. 68, No. 1, 01.01.2008, p. 22-25.

Research output: Contribution to journalArticle

Gao, B, Xie, XJ, Huang, C, Shames, DS, Chen, TTL, Lewis, CM, Bian, A, Zhang, B, Olopade, OI, Garber, JE, Euhus, DM, Tomlinson, GE & Minna, JD 2008, 'RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers', Cancer Research, vol. 68, no. 1, pp. 22-25. https://doi.org/10.1158/0008-5472.CAN-07-5183
Gao, Boning ; Xie, Xian Jin ; Huang, Chunxian ; Shames, David S. ; Chen, Tina T L ; Lewis, Cheryl M. ; Bian, Aihua ; Zhang, Bifeng ; Olopade, Olufunmilayo I. ; Garber, Judy E. ; Euhus, David M. ; Tomlinson, Gail E. ; Minna, John D. / RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers. In: Cancer Research. 2008 ; Vol. 68, No. 1. pp. 22-25.
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abstract = "The tumor suppressor gene RASSF1A regulates cell cycle progression, apoptosis, and microtubule stability and is inactivated by promoter methylation in ∼50{\%} of breast cancers. It has been shown previously that the polymorphism A133S in RASSF1A reduces its ability to regulate cell cycle progression and this polymorphism is associated with an increased risk of breast cancer. We analyzed the frequency of RASSF1A A133S in 190 Caucasian women without breast cancer and 653 patients with breast cancer including 138 BRCA1 and BRCA2 (BRCA1/2) mutation carriers, 395 non-BRCA1/2 mutations carriers, and 120 untested for BRCA1/2 mutations. Patients with breast cancer had a higher frequency of A133S than the controls [P = 0.017; odds ratios (OR), 1.71; 95{\%} confidence intervals (95{\%} CI), 1.10-2.66]. There is also a higher frequency of A133S in patients with higher familial breast cancer risk (P = 0.029; OR, 1.76; 95{\%} CI, 1.06-2.92) and patients carrying BRCA1/2 mutations (P = 0.037, OR, 1.82; 95{\%} CI, 1.04-3.18). Importantly, we found that the co-occurrence of a BRCA1 or BRCA2 mutation and A133S in RASSF1A was associated with earlier onset of breast cancer compared with those individuals with either a BRCA1/2 mutation or the A133S polymorphism alone (36.0 versus 42.0 years old, P = 0.002). Our data suggest that the presence of the RASSF1A A133S polymorphism is associated with breast cancer pathogenesis in general and modifies breast cancer age of onset in BRCA1/2 mutations carriers. Our results warrant a large-scale study to examine the effect of the A133S polymorphism in the development of breast and other types of cancers.",
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AU - Gao, Boning

AU - Xie, Xian Jin

AU - Huang, Chunxian

AU - Shames, David S.

AU - Chen, Tina T L

AU - Lewis, Cheryl M.

AU - Bian, Aihua

AU - Zhang, Bifeng

AU - Olopade, Olufunmilayo I.

AU - Garber, Judy E.

AU - Euhus, David M.

AU - Tomlinson, Gail E.

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