Risk of Breast Cancer in Women With a <i>CHEK2</i> Mutation With and Without a Family History of Breast Cancer

Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Masojć, Bartłomiej; Dębniak, Tadeusz; Górski, Bohdan; Blecharz, Paweł; Narod, Steven A.; Lubiński, Jan

doi:10.1200/jco.2010.34.0778

Cited by 230 publications

(185 citation statements)

References 37 publications

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“…Thus, the breast cancer risk estimates for c.1100delC mutation carriers are influenced by family history. The lifetime risk of breast cancer for carriers of CHEK2 truncating mutations is estimated to range from 20% for a woman with no affected relative to 44% for a woman with a first-and a second-degree relative affected (27). Interestingly, the CHEK2 missense-mutation I157T is a lower-risk allele with approximately 1.5-fold elevated cancer risk among unselected and familial cases, whereas it associates specifically with approximately fourfold increased risk of lobular breast cancer (28).…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer

Kiiski

Pelttari

Khan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

160

170

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Inherited predisposition to breast cancer is known to be caused by loss-of-function mutations in BRCA1, BRCA2, PALB2, CHEK2, and other genes involved in DNA repair. However, most families severely affected by breast cancer do not harbor mutations in any of these genes. In Finland, founder mutations have been observed in each of these genes, suggesting that the Finnish population may be an excellent resource for the identification of other such genes. To this end, we carried out exome sequencing of constitutional genomic DNA from 24 breast cancer patients from 11 Finnish breast cancer families. From all rare damaging variants, 22 variants in 21 DNA repair genes were genotyped in 3,166 breast cancer patients, 569 ovarian cancer patients, and 2,090 controls, all from the Helsinki or Tampere regions of Finland. In Fanconi anemia complementation gene M (FANCM), nonsense mutation c.5101C>T (p.Q1701X) was significantly more frequent among breast cancer patients than among controls [odds ratio (OR) = 1.86, 95% CI = 1.26-2.75; P = 0.0018], with particular enrichment among patients with triplenegative breast cancer (TNBC; OR = 3.56, 95% CI = 1.81-6.98, P = 0.0002). In the Helsinki and Tampere regions, respectively, carrier frequencies of FANCM p.Q1701X were 2.9% and 4.0% of breast cancer patients, 5.6% and 6.6% of TNBC patients, 2.2% of ovarian cancer patients (from Helsinki), and 1.4% and 2.5% of controls. These findings identify FANCM as a breast cancer susceptibility gene, mutations in which confer a particularly strong predisposition for TNBC.breast cancer | DNA repair | FANCM | exome sequencing | triple-negative breast cancer B reast cancer is the most common cancer affecting women worldwide. It is also the principal cause of death from cancer among women globally, accounting for 14% of all cancer deaths (1). The etiology of breast cancer is multifactorial, and the risk depends on various factors like age, family history, and reproductive, hormonal, or dietary factors. The majority of breast cancers are sporadic, but approximately 15% of cases show familial aggregation (2, 3). Since the identification of the first breast and ovarian cancer susceptibility genes breast cancer 1 and 2 (BRCA1 and BRCA2, respectively) by linkage analysis and positional cloning, several breast cancer susceptibility genes and alleles with different levels of risk and prevalence in the population have been recognized. BRCA1 and BRCA2 mutation carriers have more than 10-fold increased risk of breast cancer compared with women in

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Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer

Kiiski

Pelttari

Khan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

160

170

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“…Sanger sequencing identified 619 variants within the targeted region, of which eight were a common 16 base insertion not expected to be detected by NGS [13]. Of the remaining 611 Sanger identified variants; there were no false negatives within our data set, resulting in 100% sensitivity.…”

Section: Analytical Sensitivitymentioning

confidence: 92%

“…Another clinically normal sample harbored a c.1100delC variant in CHEK2. Mutations in this gene are known to be of lower penetrance, increasing a patient's risk of breast cancer or Li-Fraumeni like syndrome, but at a lower penetrance where it's not entirely unusual that we could find a mutation in a normal donor sample [3,13].…”

Section: Accuracymentioning

confidence: 97%

Clinical Validation of a Next Generation Sequencing Panel Test for Hereditary Colorectal Cancer

MJ¹,

LM²

2016

J Med Diagn Meth

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Background: Application of next generation sequencing (NGS) is revolutionizing the clinical molecular diagnostics industry. As this occurs, guidelines for validating NGS processes are limited, non-specific, and rapidly evolving. NGS validation projects are complex and expensive, so the validation experiments must be carefully considered, while being certain all current and evolving regulatory requirements are met.

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“…Raised expression of a number of genes due to single nucleotide polymorphisms (SNPs) increases the breast cancer incidence risk [4,5]. Many researchers have demonstrated that genetic polymorphisms are one of the reasons for the individual difference in the incidence of cancer [6].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-18 Gene Polymorphism and Some Risk Factors in Iraqi Patients With Breast Cancer

Al-Askeri

Jabir²,

Jaber³

2016

Asian J Pharm Clin Res

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Objective: Breast cancer is the most diagnosed cancer in women, which leads to death in a lot of women with breast cancer. The major risk factors associated with breast cancer risk related to family history, age, clinical history, lifestyle factors, long-period hormonal exposure, and single nucleotide polymorphisms in many genes showed possible links with breast cancer incidence risk in different people populations. Our study aimed to figure out the correlation between smoking, lodging and family history, and other factors with the risk of breast cancer.Methods: Blood sample from female patients with breast cancer and healthy individuals were collected and subjected to tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique for −607 C/A mutation of an interleukin (IL-18) gene and SPSS 18 software analyzed the results statically. Results:Results showed no association between lodging and smoking with risk of breast cancer, (p>0.05), while the association between the risk and family history were obvious (p<0.05). Conclusion:The results obtained by T-ARMS-PCR technique did not show the association between −607 C/An alternation of IL-18 gene and breast cancer (p>0.05) in the individuals examined in our study.

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Risk of Breast Cancer in Women With a CHEK2 Mutation With and Without a Family History of Breast Cancer

Cited by 230 publications

References 37 publications

Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer

Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer

Clinical Validation of a Next Generation Sequencing Panel Test for Hereditary Colorectal Cancer

Interleukin-18 Gene Polymorphism and Some Risk Factors in Iraqi Patients With Breast Cancer

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