Molecular Genetic Epidemiology 

Overview

For common cancers, such as breast, prostate, colorectal and lung cancers, familial risk for a person who has an affected family member is typically around 2.0; approximately 5-20% of cases are familial when two generations are considered. Based on various lines of evidence, it is unlikely that environmental factors contribute essentially to the familial clustering of any of these cancers, with the exception of lung cancer. Known susceptibility genes are estimated to explain some 15-30% of the familial clustering of breast, prostate and colorectal cancers but only about 1% of the familial clustering of lung cancer. The recently identified low-penetrance genes/loci explain a large proportion of cancer occurrence (population-attributable fraction) but explain only a small proportion of the known familial risks for these cancers. This apparent paradox is explained by the high allele frequency of the loci and the low conferred risk. However, the true functional gene variants may be much rarer and their contribution to familial risk would be higher. For many relatively common cancers, such as bladder cancer and non-Hodgkin lymphoma, only low-penetrance genes are known, and they have negligible contribution to the familial risk. Thus, there are large gaps in knowledge on the genetic basis of familial cancer that the Molecular Genetic Epidemiology group aims to address.

Significant accomplishments of the past 5 years

The Molecular Genetic Epidemiology group has:

• described familial risks and provided clinically useful risk estimates for all types of cancer (Oncologist 2008, 13:239-47).
• described familial clustering of histology-specific nervous system tumors (Lancet Oncol 2009 10:481-8).
• shown that mortality in cancers such as prostate cancer is familial, which is likely to be explained by inherited prognosis-related genes (J Clin Oncol 2008, 26:1705-9).
• provided guidelines for cancer screening in individuals with a family history of breast and prostate cancers (Oncologist 2009, 14:1209-17).
• participated in a number of studies to find low-penetrance genes for colorectal, breast, skin, nervous sytem and bladder cancers and for melanoma and childhood leukemia Nat Genet 2008, 40:623-30; Nat Genet 2009, 41:221-7; Nat Genet 2009, 41:899-904; Nat Genet 2009, 41:909-14; Blood 2010, 115:1765-7).
  

5 most significant publications of the past 5 years

Hemminki K, Ji J, Försti A, Sundquist J, Lenner P: Concordance of survival in family members with prostate cancer. J Clin Oncol 2008, 26:1705-9

Hemminki K, Lenner P, Sundquist J, Lorenzo Bermejo J: Risk of subsequent solid tumors after non-Hodgkin lymphoma: effect of diagnostic age and time since diagnosis. J Clin Oncol 2008, 26:1850-7

Tomlinson IP, Webb E, Carvajal-Carmona L, …,  Hemminki K, Vodicka P, Naccarati A, Lipton L, Ho JW, Cheng KK, Sham PC, Luk J, Agúndez JA, Ladero JM, de la Hoya M, Caldés T, Niittymäki I, Tuupanene S, Karhu A, Aaltonen L, Cazier JB, Campbell H, Dunlop MG, Houlston RS: A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet 2008, 40:623-30

Anderson LA, Pfeiffer RM, Rapkin JS, Gridley G, Mellemkjaer L, Hemminki K, Björkholm M, Goldin LR, Caporaso NR, Landgren O: Survival patterns among lymphoma patients with a family history of lymphoma. J Clin Oncol 2008, 26:4958-65

Hemminki K, Tretli S, Sundquist J, Johannesen TB, Granström C; Familial risks in nervous system tumours: histology-specific analysis from Sweden and Norway. Lancet Oncol 2009, 10:481-88

Contact

Prof. Dr. Kari Hemminki
German Cancer Research Center (DKFZ)
Molecular Genetic Epidemiology
Im Neuenheimer Feld 580
69120 Heidelberg

Tel: 06221.421800
Fax: 06221.421810
k.hemminki@dkfz.de

News

Felix Burda Awards was granted to DKFZ and NCT for engagement in the colon cancer prevention 

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