Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2013
HOXB13 mutation and prostate cancer: studies of siblings and aggressive disease.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Witte John S, Mefford Joel, Plummer Sarah J, Liu Jinghua, Cheng Iona, Klein Eric A, Rybicki Benjamin A, Casey Graham
Аннотация
BACKGROUND: Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans.
METHODS: We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans.
RESULTS: In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10(-17)), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P < 1 × 10(-5).
CONCLUSIONS: The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men.
IMPACT: Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer.
METHODS: We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans.
RESULTS: In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10(-17)), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P < 1 × 10(-5).
CONCLUSIONS: The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men.
IMPACT: Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer.