Mutations in the CHEK2 gene increase the risk of breast cancer, particularly among women who also have a family history of the disease. These results were published in the Journal of Clinical Oncology.
Mutations in the BRCA1 and BRCA2 genes are known to greatly increase a woman’s lifetime risk of breast and ovarian cancer, but mutations in other genes—such as CHEK2—are likely to contribute to breast cancer risk as well.
Mutations in the CHEK2 gene have been reported to increase breast cancer risk by up to three-fold. The risk associated with a CHEK2 mutation, however, may vary by a woman’s family history of breast cancer. CHEK2 mutations may increase breast cancer risk to a greater extent among women with a family history of the disease.
To explore the relationships among CHEK2 mutations, family history of breast cancer, and risk of breast cancer, researchers conducted a study in Poland. Information was collected about more than 7,000 women with BRCA1-negative breast cancer and more than 4,000 women without breast cancer.
The researchers considered both first-degree and second-degree family history of breast cancer. First-degree relatives are parents, offspring, and siblings. Second-degree relative are grandparents, grandchildren, aunts and uncles, nephews and nieces, and half siblings.
- A particular type of CHEK2 mutation (a truncating mutation) was found in 3% of the women with breast cancer and in less than 1% of the women without breast cancer.
- Among women with a first- or second-degree family history of breast cancer, risk of breast cancer was five times higher among those with a CHEK2 mutation than among those without a CHEK2 mutation. Among women without a family history of breast cancer, risk of breast cancer was three-times higher among those with a CHEK2 mutation.
- Assuming a lifetime risk of breast cancer of 6% (the general-population risk seen in Poland; this is lower than what is seen in the United States), the lifetime risk of breast cancer for a woman with a CHEK2 mutation was estimated to be 20% if there was no family history of breast cancer, 28% if one second-degree relative had breast cancer, 34% if one first-degree relative had breast cancer, and 44% if both a first- and second-degree relative had breast cancer.
Because patterns of gene mutations and baseline risks of breast cancer differ across countries, these results may not be applicable to the United States. The results suggest, however, that CHEK2 gene mutations do contribute to some cases of breast cancer, and that risk may be particularly high for women who have both a CHEK2 gene mutation and a family history of breast cancer.
Reference: Cybulski C, Wokolorczyk D, Jakubowska A et al. Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. Journal of Clinical Oncology. Early online publication August 29, 2011.
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