The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting.
Patients and Methods
Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2∗1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2∗1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n = 2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2∗1100delC status of relatives was unknown.
Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4–2.7), p < 0.001) was observed in sisters of CHEK2∗1100delC positive index cases compared to sisters of CHEK2∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0–2.4) for mothers of CHEK2 positive versus negative index cases (p = 0.041). For second primary breast cancers HR was increased in CHEK2∗1100delC positive index cases (HR 2.1, 95% CI: 1.3–3.3, p = 0.003) and their sisters (HR 2.6, 95% CI: 1.1–6.1, p = 0.025).
There is an excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive non-BRCA1/2 familial breast cancer patients compared to non-CHEK2∗1100delC familial breast cancer relatives.
Genotyping for the CHEK2∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs.
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- Low-penetrance susceptibility to breast cancer due to CHEK2∗1100delC in noncarriers of BRCA1 or BRCA2 mutations.Nat Genet. 2002; 31: 55-59
- CHK2 kinase: cancer susceptibility and cancer therapy – two sides of the same coin?.Nat Rev Cancer. 2007; 7: 925-936
- CHEK2∗1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9065 controls from 10 studies.Am J Hum Genet. 2004; 74: 1175-1182
- Testing for CHEK2 in the cancer genetics clinic: ready for prime time?.Clin Genet. 2010; 78: 1-7
- Family history, genetic testing, and clinical risk prediction: pooled analysis of CHEK2∗1100delC in 1828 bilateral breast cancers and 7030 controls.Cancer Epidemiol Biomarkers Prev. 2009; 18: 230-234
- CHEK2∗1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls.J Clin Oncol. 2008; 26: 542-548
- Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.J Clin Oncol. 2011; 29: 3747-3752
- Polygenic susceptibility to breast cancer and implications for prevention.Nat Genet. 2002; 31: 33-36
- The CHEK2∗1100delC variant acts as a breast cancer risk modifier in non-BRCA1/2 multiple-case families.Cancer Res. 2003; 63: 8153-8157
- Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58209 women with breast cancer and 101986 women without the disease.Lancet. 2001; 358: 1389-1399
- Time to check CHEK2 in families with breast cancer?.J Clin Oncol. 2008; 26: 519-520
- CHEK2, breast cancer, and the understanding of clinical utility.Clin Genet. 2010; 78: 8-10
- CHEK2∗1100delC homozygosity is associated with a high breast cancer risk in women.J Med Genet. 2011; 48: 860-863
- Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband.Br J Cancer. 2009; 100: 1508-1512
- CHEK2 1100delC is a susceptibility allele for HNPCC-related colorectal cancer.Clin Cancer Res. 2008; 14: 4989-4994
- Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility.Eur J Cancer. 2011; 47: 2546-2551
- Risk of breast cancer in families of multiple affected women and men.Breast Cancer Res Treat. 2011; 132: 723-728
- Interaction between CHEK2∗1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study.Lancet. 2005; 366: 1554-1557
- Excess risk for contralateral breast cancer in CHEK2∗1100delC germline mutation carriers.Breast Cancer Res Treat. 2004; 83: 91-93
- Risk for contralateral breast cancer among carriers of the CHEK2∗1100delC mutation in the WECARE Study.Br J Cancer. 2008; 98: 728-733
- BRCA1, BRCA2 and CHEK2 c.1100 delC mutations in patients with double primaries of the breasts and/or ovaries.J Med Genet. 2010; 47: 561-566
- A multicenter study of cancer incidence in CHEK2 1100delC mutation carriers.Cancer Epidemiol Biomarkers Prev. 2006; 15: 2542-2545
Published online: February 18, 2013
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