TY  - JOUR
AU  - Zheng, Guoqiao
AU  - Catalano, Calogerina
AU  - Bandapalli, Obul Reddy
AU  - Paramasivam, Nagarajan
AU  - Chattopadhyay, Subhayan
AU  - Schlesner, Matthias
AU  - Sijmons, Rolf
AU  - Hemminki, Akseli
AU  - Dymerska, Dagmara
AU  - Lubinski, Jan
AU  - Hemminki, Kari
AU  - Försti, Asta
TI  - Cancer Predisposition Genes in Cancer-Free Families.
JO  - Cancers
VL  - 12
IS  - 10
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2020-02078
SP  - 2770
PY  - 2020
N1  - #EA:C050#LA:B062#LA:C050#LA:C020#
AB  - Familial clustering, twin concordance, and identification of high- and low-penetrance cancer predisposition variants support the idea that there are families that are at a high to moderate excess risk of cancer. To what extent there may be families that are protected from cancer is unknown. We wanted to test genetically whether cancer-free families share fewer breast, colorectal, and prostate cancer risk alleles than the population at large. We addressed this question by whole-genome sequencing (WGS) of 51 elderly cancer-free individuals whose numerous (ca. 1000) family members were found to be cancer-free ('cancer-free families', CFFs) based on face-to-face interviews. The average coverage of the 51 samples in the WGS was 42x. We compared cancer risk allele frequencies in cancer-free individuals with those in the general population available in public databases. The CFF members had fewer loss-of-function variants in suggested cancer predisposition genes compared to the ExAC data, and for high-risk cancer predisposition genes, no pathogenic variants were found in CFFs. For common low-penetrance breast, colorectal, and prostate cancer risk alleles, the results were not conclusive. The results suggest that, in line with twin and family studies, random environmental causes are so dominant that a clear demarcation of cancer-free populations using genetic data may not be feasible.
LB  - PUB:(DE-HGF)16
C6  - pmid:32992489
DO  - DOI:10.3390/cancers12102770
UR  - https://inrepo02.dkfz.de/record/163838
ER  -