Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility

Jong, Mirjam M. de; Nolte, Ilja M.; Meerman, Gerard J. te; Graaf, Winette T.A. van der; Oosterwijk, Jan C.; Kleibeuker, Jan H.; Schaapveld, Michael; Vries, Elisabeth G.E. de

doi:10.1136/jmg.39.4.225

Cited by 203 publications

(136 citation statements)

References 246 publications

(173 reference statements)

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“…Some of the remaining 20% of cases are associated with mutations of various genes: e.g., Cowden syndrome (the PTEN tumor suppressor), , and the androgen receptor (Harris et al, 1992;Cannon-Albright and Skolnick, 1996;Greene, 1997). These known genes do not account for 100% of hereditary breast cancers, suggesting there may another susceptibility gene (BRCA3) to be discovered (de Jong et al, 2002).…”

Section: Hereditary Breast Cancersmentioning

confidence: 99%

BRCA1 gene in breast cancer

Rosen

Fan

Pestell

et al. 2003

Journal Cellular Physiology

242

195

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The BRCA1 gene was identified and cloned in 1994 based on its linkage to early onset breast cancer and breast-ovarian cancer syndromes in women. While inherited mutations of BRCA1 are responsible for about 40-45% of hereditary breast cancers, these mutations account for only 2-3% of all breast cancers, since the BRCA1 gene is rarely mutated in sporadic breast cancers. However, BRCA1 expression is frequently reduced or absent in sporadic cancers, suggesting a much wider role in mammary carcinogenesis. Since BRCA1 was cloned in 1994, its molecular function has been the subject of intense investigation. These studies have revealed multiple functions of the BRCA1 that may contribute to its tumor suppressor activity, including roles in: cell cycle progression, several highly specialized DNA repair processes, DNA damage-responsive cell cycle checkpoints, regulation of a set of specific transcriptional pathways, and apoptosis. Many of these functions are linked to protein:protein interactions involving different portions of the 1,863 amino acid (aa) BRCA1 protein. BRCA1 functions in cell cycle progression and the DNA damage response appear to be regulated by distinct and specific phosphorylation events, but the molecular pathways activated by these phosphorylations are only beginning to be unraveled. In addition, the reason that BRCA1 mutation carriers develop specific tumor types (breast and ovarian cancers in women and possibly prostate cancers in men) is not clearly understood. Elucidation of the precise molecular functions of the BRCA1 gene product will greatly enhance our understanding of the pathogenesis of hereditary as well as sporadic mammary carcinogenesis.

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Section: Hereditary Breast Cancersmentioning

confidence: 99%

BRCA1 gene in breast cancer

Rosen

Fan

Pestell

et al. 2003

Journal Cellular Physiology

242

195

View full text Add to dashboard Cite

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“…Patients with Petz-Jeghers syndrome have been found to be at increased risk of breast cancer (Boardman et al, 1998). This syndrome is caused by truncating mutations in the LKB1 gene, but its involvement in breast cancer appears to be only in patients with the syndrome (Hemminki et al, 1998;Jenne et al, 1998;de Jong et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Models of genetic susceptibility to breast cancer

2006

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One of the most important risk factors for breast cancer is family history of the disease, indicating that genetic factors are important determinants of breast cancer risk. A number of breast cancer susceptibility genes have been identified, the most important being BRCA1 and BRCA2. However, it is estimated that all the currently known breast cancer susceptibility genes accounts for less than 25% of the familial aggregation of breast cancer. In this paper, we review the evidence for other breast cancer susceptibility genes arising from twin studies, pedigree analysis and studies of phenotypes associated with breast cancer, and the progress towards finding other breast cancer susceptibility genes through linkage and association studies. Taken together, the available evidence indicates that susceptibility to breast cancer is mediated through variants in many genes, each conferring a moderate risk of the disease. Such a model of susceptibility has implications for both risk prediction and for future gene identification studies.

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“…DNA DSB repair pathways are of etiologic importance during tumorigenesis, particularly breast cancer tumorigenesis. Several high-penetrant mutations in DSB repair genes have been found to be involved in breast cancer, including BRCA1, BRCA2, and ATM (12). As high-penetrant mutations explain only a small percentage of breast cancer, recent efforts have focused on common variants in DNA repair pathways, and nominally, significant results have been observed (13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

A Role for XRCC4 in Age at Diagnosis and Breast Cancer Risk

Allen‐Brady

Cannon‐Albright

Neuhausen

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Genetic variants in DNA repair genes influence the ability to repair damaged DNA. Unrepaired or improperly repaired DNA may lead to genetic instability and carcinogenesis. We evaluated the role of four tagging single nucleotide polymorphisms (tSNP) in the DNA repair gene, XRCC4, and its association with breast cancer risk and age at diagnosis of breast cancer in 464 cases and 576 controls selected to be BRCA1/2 mutation negative from high-risk Utah pedigrees. We observed a significant association for two 4-locus tSNP haplotypes and age at diagnosis. Carriage of one haplotype was associated with later diagnosis (haplotype frequency, 0.039; mean age at diagnosis, 67.17 years; P = 0.001), and carriage of the other was associated with earlier diagnosis (haplotype frequency, 0.214; mean age at diagnosis, 54.04 years; P = 0.0085). For breast cancer risk, two 2-locus tSNP haplotypes explained the observed association as well as extended four-locus haplotypes. The two 2-locus haplotypes were nominally associated with breast cancer risk, one for reduced risk (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = 0.014) and one for increased risk (odds ratio, 1.30; 95% confidence interval, 1.02-1.67; P = 0.033). Moreover, one of the tSNPs is in strong linkage disequilibrium (D ¶ = 1.00) with an XRCC4 SNP found to be significantly associated with breast cancer risk in Taiwan, hence, confirming their findings. Our results suggest that XRCC4 may play a role in the age at diagnosis and risk of breast cancer in non-BRCA1/2, heritable breast cancer cases. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1306-10)

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Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility

Cited by 203 publications

References 246 publications

BRCA1 gene in breast cancer

BRCA1 gene in breast cancer

Models of genetic susceptibility to breast cancer

A Role for XRCC4 in Age at Diagnosis and Breast Cancer Risk

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