Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study

Broeks, Annegien; Braaf, Linde M.; Huseinovic, Angelina; Nooijen, Anke; Urbanus, Jos; Hogervorst, Frans B.L.; Schmidt, Marjanka K.; Klijn, Jan G.M.; Russell, Nicola S.; Leeuwen, Flora E. van; Veer, Laura J. van ’t

doi:10.1186/bcr1668

Cited by 82 publications

(54 citation statements)

References 38 publications

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“…5,[13][14][15][16][17][18][19] For homozygous carriers, our observations indicate that (contralateral) breast cancer risk may be as high as to justify preventive mastectomy (or at least intensified screening), but longitudinal studies on more cases are needed to arrive at more accurate risk estimates.…”

Section: Discussionmentioning

confidence: 93%

“…3,[10][11][12][13] Breast cancer patients heterozygous for 1100delC also have an increased risk of developing contralateral breast cancer when compared with wild-type breast cancer patients. 5,[13][14][15][16][17][18][19][20] The contralateral breast cancer risk may be even higher when radiotherapy has been given to treat the first tumor. 15,19 It must be noted that in women who also carry a pathogenic BRCA1/2 mutation the 1100delC allele does not seem to modify breast cancer risk.…”

Section: Introductionmentioning

confidence: 99%

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CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

et al. 2013

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The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4-32.6, P ¼ 0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

et al. 2013

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“…The germline mutation 1100delC truncates the CHEK2 protein, thereby abolishing the kinase function (Wu et al, 2001). Epidemiological evidence to substantiate increased radiosensitivity among carriers is, however, sparse (Bernstein et al, 2006;Broeks et al, 2007). Also, although a study conducted in Belgium suggested that breast cancer patients with a CHEK2*1100-delC mutation are, in general, not characterised by a distinct enhanced chromosomal radiosensitivity, this conclusion was based on only four breast cancer cases with the mutation who were compared with healthy controls without the mutation (Baeyens et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

et al. 2008

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The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985 -1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR) ¼ 1.8, 95% confidence interval (CI) ¼ 0.6 -5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI ¼ 0.8 -8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.

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“…Our study provides additional insights into the findings of the few published studies that have examined risk of CBC associated with RT among BRCA1/BRCA2 carriers (12,(26)(27)(28)(29)(30). The multi-center follow-up study of breast cancer patients attending high risk clinics conducted by Pierce and colleagues (28, 31) compared patients treated with breastconserving surgery and RT.…”

Section: Discussionmentioning

confidence: 95%

“…Their finding of an increased risk of CBC among carriers is also consistent with ours. In a case-only study, Broeks et al examined 247 CBC cases to identify carriers of a germline mutation in ATM, BRCA1/BRCA2, or CHEK2 (26) and found an interaction of RT with carriers of these mutations. However, this study only examined risk by aggregating genes and the extent of interaction attributable to BRCA1/BRCA2 carrier status was not reported.…”

Section: Discussionmentioning

confidence: 99%

Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report

Recht¹

2014

Breast Diseases: A Year Book Quarterly

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Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study

Abstract: Introduction Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer.

Cited by 82 publications

References 38 publications

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report

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