DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F20%3A00518088" target="_blank" >RIV/68378041:_____/20:00518088 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/20:10396555 RIV/00216208:11140/20:10396555

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32516" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32516</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ijc.32516" target="_blank" >10.1002/ijc.32516</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Popis výsledku v původním jazyce

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 x 10(-6)) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 x 10(-6)). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 x 10(-6). Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.

Název v anglickém jazyce

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Popis výsledku anglicky

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 x 10(-6)) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 x 10(-6)). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 x 10(-6). Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30302 - Epidemiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Cancer

ISSN

0020-7136

e-ISSN

—

Svazek periodika

146

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

363-372

Kód UT WoS článku

000498734300006

EID výsledku v databázi Scopus

2-s2.0-85068514355