Age-specific familial risks in cancer as clues to germline genetic and environmental causes: focus on colorectal, endometrial, prostate, kidney, breast and lung cancers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F25%3A10494730" target="_blank" >RIV/00216208:11140/25:10494730 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lMN_kXGXGK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lMN_kXGXGK</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13053-024-00301-8" target="_blank" >10.1186/s13053-024-00301-8</a>

Result language

angličtina

Original language name

Age-specific familial risks in cancer as clues to germline genetic and environmental causes: focus on colorectal, endometrial, prostate, kidney, breast and lung cancers

Original language description

BACKGROUND: The Swedish Family-Cancer Database (FCD) is the largest source of data on familial cancer in the world, including practically complete family structures and individual cancer diagnoses from the high-quality cancer registry. We present a novel application of FCD by analyzing age-specific familial risks and interpreting them through likely causes, such as germline pathogenic variants and/or environmental exposures. MAIN BODY: The basic assumption for this approach is that a discrete familial clustering in a narrow age-interval is not random but may provide causal clues. For this analysis we selected reasonably common cancers to meaningfully scrutinize familial risk through adulthood in which cancers are diagnosed, that included colorectal (CRC) and endometrial cancers, prostate and kidney cancers and breast and lung cancers. The interpretation is based on the literature. The highest familial relative risks for CRC and endometrial cancers were found at ages 40-44 years, matching the peak impact of mismatch repair gene mutations. However endometrial cancer showed also a small early onset component which could not be explained. Age-related familial risks for breast, prostate and kidney cancers also matched data from large-scale sequencing; these included the early onset component in kidney cancer which was likely due to VHL mutations. Age distribution of familial lung cancer was unique in showing a wide peak extending from middle to old ages, which would be consistent with a combination of direct genetic effects and indirect influence on inheritance of smoking dependence. CONCLUSIONS: The present review of age-specific familial risks and age-of-onset data from the literature may allow an interpretation that the familial and germline landscapes are reasonably harmonious for relatively early onset cancers but at higher ages no discrete peaks can be found which may implicate attenuated impact of high-risk genes and polygenic influence.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Hereditary Cancer in Clinical Practice

ISSN

1731-2302

e-ISSN

1897-4287

Volume of the periodical

23

Issue of the periodical within the volume

1

Country of publishing house

PL - POLAND

Number of pages

9

Pages from-to

7

UT code for WoS article

001428255000003

EID of the result in the Scopus database

2-s2.0-85218421545