CHEK2-Positive Breast Cancers in Young Polish Women

• Published in: Clinical cancer research Vol. 12; no. 16; pp. 4832 - 4835
• Main Authors: CYBULSKI, Cezary, GORSKI, Bohdan, NAROD, Steven A, LUBINSKI, Jan, HUZARSKI, Tomasz, BYRSKI, Tomasz, GRONWALD, Jacek, DEBNIAK, Tadeusz, WOKOŁORCZYK, Dominika, JAKUBOWSKA, Anna, KOWALSKA, Elzbieta, OSZUREK, Oleg
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-08-2006
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Checkpoint Kinase 2; CHEK2; CHK2; Female; gene; germ line mutations; Gynecology. Andrology. Obstetrics; Humans; Infant, Newborn; Male; Mammary gland diseases; Medical sciences; Middle Aged; Mutation; Pharmacology. Drug treatments; Poland - epidemiology; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - genetics; tumor characteristics; Tumors; Poland; Europe; Human; Mammary gland diseases; Breast cancer; Malignant tumor; Young adult
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-0158

Purpose: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers.
Experimental Design: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2 -positive cases and CHEK2 -negative cases were compared.
Results: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups.
Conclusion: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.