The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

Koppert, Linetta B.; Schutte, Mieke; Abbou, Mustaffa; Tilanus, Hugo W.; Dinjens, Winand N.M.

doi:10.1038/sj.bjc.6601551

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…Our findings support those of recent case-control studies that have also found no significant association between the CHEK2 1100delC mutation and non -breast cancers (8,(30)(31)(32)(33). There was some evidence for an increase in the risk of cancer before the age of 50 years, although the only cancer sites for which this was statistically significant were lung and colorectal cancer.…”

Section: Discussionsupporting

confidence: 80%

A Multicenter Study of Cancer Incidence in CHEK2 1100delC Mutation Carriers

Thompson

Seal

Schutte

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The CHEK2 1100delC protein-truncating mutation has a carrier frequency of f0.7% in Northern and Western European populations and confers an f2-fold increased risk of breast cancer. It has also been suggested to increase risks of colorectal and prostate cancer, but its involvement with these or other types of cancer has not been confirmed. The incidence of cancer other than breast cancer in 11,116 individuals from 734 non-BRCA1/2 breast cancer families from the United Kingdom, Germany, Netherlands, and the United States was compared with that predicted by population rates. Relative risks (RR) to carriers and noncarriers were estimated by maximum likelihood, via the expectation-maximization algorithm to allow for unknown genotypes. Sixty-seven families contained at least one tested CHEK2 1100delC mutation carrier. There was evidence of underreporting of cancers in male relatives (422 cancers observed, 860 expected) but not in females (322 observed, 335 expected); hence, we focused on cancer risks in female carriers. The risk of cancers other than breast cancer in female carriers was not significantly elevated, although a modest increase in risk could not be excluded (RR, 1.18; 95% confidence interval, 0.64-2.17). The carrier risk was not significantly raised for any individual cancer site, including colorectal cancer (RR, 1.60; 95% confidence interval, 0.54-4.71). However, between ages 20 to 50 years, the risks of colorectal and lung cancer were both higher in female carriers than noncarriers (P = 0.041 and 0.0001, respectively). There was no evidence of a higher prostate cancer risk in carriers than noncarriers (P = 0.26), although underreporting of male cancers limited our power to detect such a difference. Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2542 -5)

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Section: Discussionsupporting

confidence: 80%

A Multicenter Study of Cancer Incidence in CHEK2 1100delC Mutation Carriers

Thompson

Seal

Schutte

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In humans, it is located in 22q12.1, and encodes a cell cycle checkpoint kinase that is implicated in DNA damage responses (9,19) . Following the occurrence of double-stranded DNA breaks, CHEK2 is activated through phosphorylation by ATM.…”

Section: Introductionmentioning

confidence: 99%

CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families

Abud

Prolla

Koehler‐Santos³

et al. 2012

Arq. Gastroenterol.

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-Context -CHEK2 encodes a cell cycle checkpoint kinase that plays an important role in the DNA damage repair pathway, activated mainly by ATM (Ataxia Telangiectasia Mutated) in response to double-stranded DNA breaks. A germline mutation in CHEK2, 1100delC, has been described as a low penetrance allele in a significant number of families with breast and colorectal cancer in certain countries and is also associated with increased risk of contralateral breast cancer in women previously affected by the disease. About 5%-10% of all breast and colorectal cancers are associated with hereditary predisposition and its recognition is of great importance for genetic counseling and cancer risk management. Objectives -Here, we have assessed the frequency of the CHEK2 1100delC mutation in the germline of 59 unrelated Brazilian individuals with clinical criteria for the hereditary breast and colorectal cancer syndrome. Methods -A long-range PCR strategy followed by gene sequencing was used. Results -The 1100delC mutation was encountered in the germline of one (1.7%) individual in this high risk cohort. This indicates that the CHEK2 1100delC is not commonly encountered in Brazilian families with multiple diagnoses of breast and colorectal cancer. Conclusion -These results should be confirmed in a larger series of families and further testing should be undertaken to investigate the molecular mechanisms underlying the hereditary breast and colorectal cancer phenotype.

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“…In an esophageal cancer study, Koppert et al found 1.5% of 551 cases and 1.4% of 644 controls carry the CHEK2 ∗ 1100delC mutation [ 63 ]. Similarly, there is no patient with CHEK2 ∗ 1100delC mutation among 91 German head and neck cancer patients [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, there is no patient with CHEK2 ∗ 1100delC mutation among 91 German head and neck cancer patients [ 64 ]. Therefore, the authors concluded that the CHEK2 ∗ 1100delC mutation has no major contribution in carcinogenesis in the esophagus [ 63 ] and head and neck [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

CHEK2^∗1100delC Mutation and Risk of Prostate Cancer

2014

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Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 ∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating that CHEK2 ∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

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The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

Cited by 7 publications

References 25 publications

A Multicenter Study of Cancer Incidence in CHEK2 1100delC Mutation Carriers

A Multicenter Study of Cancer Incidence in CHEK2 1100delC Mutation Carriers

CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families

CHEK2^∗1100delC Mutation and Risk of Prostate Cancer

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The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

Cited by 7 publications

References 25 publications

A Multicenter Study of Cancer Incidence in CHEK2 1100delC Mutation Carriers

A Multicenter Study of Cancer Incidence in CHEK2 1100delC Mutation Carriers

CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families

CHEK2∗1100delC Mutation and Risk of Prostate Cancer

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CHEK2^∗1100delC Mutation and Risk of Prostate Cancer