CHEK2 Is a Multiorgan Cancer Susceptibility Gene

• Published in: American journal of human genetics Vol. 75; no. 6; pp. 1131 - 1135
• Main Authors: Cybulski, C., Górski, B., Huzarski, T., Masojć, B., Mierzejewski, M., Dębniak, T., Teodorczyk, U., Byrski, T., Gronwald, J., Matyjasik, J., Złowocka, E., Lenner, M., Grabowska, E., Nej, K., Castaneda, J., Mędrek, K., Szymańska, A., Szymańska, J., Kurzawski, G., Suchy, J., Oszurek, O., Witek, A., Narod, S.A., Lubiński, J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-12-2004; University of Chicago Press; The American Society of Human Genetics
• Subjects: Biological and medical sciences; Case-Control Studies; Checkpoint Kinase 2; DNA Primers; Gene Frequency; Genetic Predisposition to Disease - genetics; Genetic Variation; Humans; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - genetics; Odds Ratio; Poland; Polymorphism, Restriction Fragment Length; Protein-Serine-Threonine Kinases - genetics; Tumors; Poland; Human; Sensitivity; Chek2 gene; Multiple; Genetics; Malignant tumor; Genetic determinism
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/426403

A single founder allele of the
CHEK2 gene has been associated with predisposition to breast and prostate cancer in North America and Europe. The CHEK2 protein participates in the DNA damage response in many cell types and is therefore a good candidate for a multisite cancer susceptibility gene. Three founder alleles are present in Poland. Two of these result in a truncated CHEK2 protein, and the other is a missense substitution of an isoleucine for a threonine. We ascertained the prevalence of each of these alleles in 4,008 cancer cases and 4,000 controls, all from Poland. The majority of the common cancer sites were represented. Positive associations with protein-truncating alleles were seen for cancers of the thyroid (odds ratio [OR] 4.9;
P=.0006), breast (OR 2.2;
P=.02), and prostate (OR 2.2;
P=.04). The missense variant I157T was associated with an increased risk of breast cancer (OR 1.4;
P=.02), colon cancer (OR 2.0;
P=.001), kidney cancer (OR 2.1;
P=.0006), prostate cancer (OR 1.7;
P=.002), and thyroid cancer (OR 1.9;
P=.04). The range of cancers associated with mutations of the
CHEK2 gene may be much greater than previously thought.