Evaluation of early-life factors and early-onset colorectal cancer among men and women in the UK Biobank

Author(s):  
Valerie Gausman ◽  
Peter S. Liang ◽  
Kelli O’Connell ◽  
Elizabeth D. Kantor ◽  
Mengmeng Du
2020 ◽  
Vol 158 (6) ◽  
pp. S-496
Author(s):  
Arif A. Arif ◽  
Daljeet Chahal ◽  
Caroline Speers ◽  
Mary A. De Vera ◽  
Sharlene Gill ◽  
...  

Author(s):  
Jeong Eun Kim ◽  
Jaeyong Choi ◽  
Chang-Ohk Sung ◽  
Yong Sang Hong ◽  
Sun Young Kim ◽  
...  

AbstractThe global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Author(s):  
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  
...  

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Luisa Saldana Ortega ◽  
Kathryn E. Bradbury ◽  
Amanda J. Cross ◽  
Jessica S. Morris ◽  
Marc J. Gunter ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Z Raisi-Estabragh ◽  
A Jaggi ◽  
N Aung ◽  
S Neubauer ◽  
S Piechnik ◽  
...  

Abstract Introduction Cardiac magnetic resonance (CMR) radiomics use voxel-level data to derive quantitative indices of myocardial tissue texture, which may provide complementary risk information to traditional CMR measures. Purpose In this first stage of our work, establishing the performance characteristics of CMR radiomics in relation to disease outcomes, we aimed to elucidate differences in radiomic features by sex and age in apparently healthy adults. Methods We defined a healthy cohort from the first 5,065 individuals completing the UK Biobank Imaging Enhancement, limiting to white Caucasian ethnicity, and excluding those with major co-morbidities, or cardiovascular risk factors/symptoms. We created evenly distributed age groups: 45–54 years, 55–64 years, 65–74 years. Radiomics features were extracted from left ventricle segmentations, with normalisation to body surface area. We compared mean values of individual features between the sexes, stratified by age and separately between the oldest and youngest age groups for each sex. Results We studied 657 (309 men, 358 women) healthy individuals. There were significant differences between radiomics features of men and women. Different features appeared more important at different age groups. For instance, in the youngest age group “end-systolic coarseness” showed greatest difference between men and women, whilst “end-diastolic run percentage” and “end-diastolic high grey level emphasis” showed most variation in the oldest and middle age groups. In the oldest age groups, differences between men and women were most predominant in the texture features, whilst in the younger groups a mixture of shape and texture differences were observed. We demonstrate significant variation between radiomics features by age, these differences are exclusively in texture features with different features implicated in men and women (“end-diastolic mean intensity” in women, “end-systolic sum entropy in men”). Conclusions There are significant age and sex differences in CMR radiomics features of apparently healthy adults, demonstrating alterations in myocardial architecture not appreciated by conventional indices. In younger ages, shape and texture differences are observed, whilst in older ages texture differences dominate. Furthermore, texture features are the most different features between the youngest and oldest hearts. We provide proof-of-concept data indicating CMR radiomics has discriminatory value with regard to two characteristics strongly linked to cardiovascular outcomes. We will next elucidate relationships between CMR radiomics, cardiac risk factors, and clinical outcomes, establishing predictive value incremental to existing measures. Funding Acknowledgement Type of funding source: Other. Main funding source(s): European Union's Horizon 2020 research and innovation programme (825903),British Heart Foundation Clinical Research Training Fellowship (FS/17/81/33318)


2021 ◽  
Author(s):  
Jinhee Hur ◽  
Ebunoluwa Otegbeye ◽  
Hee-Kyung Joh ◽  
Katharina Nimptsch ◽  
Kimmie Ng ◽  
...  

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