Gronwald J, Cybulski C, Piesiak W, Suchy J, Huzarski T, Byrski T, Gorski B, Debniak T, Szwiec M, Wokolowczyk D, Matuszewski M, Sun P, Lubinski J, Narod S A
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Br J Cancer. 2009 May 5;100(9):1508-12. doi: 10.1038/sj.bjc.6605038.
It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1-6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2-8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4-7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer.
准确了解与各种CHEK2突变相关的癌症范围以及每种突变所对应的终生癌症风险非常重要。我们希望确定携带CHEK2突变的家族中家族病史、突变类型与癌症风险之间的关系。我们从波兰各地的医院收集了2012名未经挑选的乳腺癌女性、2007名前列腺癌男性以及1934名结肠癌患者的血样和家系信息。对所有5953份样本进行了4种CHEK2始祖突变的基因检测，共鉴定出533名携带者。我们估计，2544名一级亲属在75岁前患任何癌症的风险为22.3%。在调整突变类型后，乳腺癌先证者的亲属患乳腺癌的风险远高于前列腺癌或结肠癌患者的亲属（风险比=3.6；95%置信区间=2.1 - 6.2；P = 0.0001）。同样，前列腺癌先证者的亲属患前列腺癌的风险高于乳腺癌或结肠癌患者的亲属（风险比=4.4；95%置信区间=2.2 - 8.7；P = 0.0001），结肠癌先证者的亲属患结肠癌的风险高于前列腺癌或乳腺癌患者的亲属（风险比=4.2；95%置信区间=2.4 - 7.
