scholarly journals APC Mutations Are Not Confined to Hotspot Regions in Early-Onset Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3829
Author(s):  
Alan Aitchison ◽  
Christopher Hakkaart ◽  
Robert C. Day ◽  
Helen R. Morrin ◽  
Frank A. Frizelle ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Young People ◽  
Early Onset ◽  
Older Patients ◽  
High Rate ◽  
Early Event ◽  
Mutation Status ◽  
Apc Mutations ◽  
Apc Mutation ◽  
Early Onset Colorectal Cancer

While overall colorectal cancer (CRC) cases have been declining worldwide there has been an increase in the incidence of the disease among patients under 50 years of age. Mutation of the APC gene is a common early event in CRC but is reported at lower rates in early-onset colorectal cancer (EOCRC) than in older patients. Here we investigate the APC mutation status of a cohort of EOCRC patients in New Zealand using a novel sequencing approach targeting regions of the gene encompassing the vast majority of known APC mutations. Using this strategy we find a higher rate (72%) of APC mutation than previously reported in EOCRC with mutations being spread throughout the gene rather than clustered in hotspots as seen with sporadic mutations in older patients. The rate of mutations falling within hotspots was similar to those previously seen in EOCRC and as such our study has implications for sequencing strategies for EOCRC patients. Overall there were low rates of both loss of heterozygosity and microsatellite instability whereas a relatively high rate (40%) of APC promoter methylation was found, possibly reflecting increasing exposure of young people to pro-oncogenic lifestyle factors.

scholarly journals The gut microbiome and potential implications for early-onset colorectal cancer

2020 ◽  
Vol 9 (3) ◽  
pp. CRC25
Author(s):  
Reetu Mukherji ◽  
Benjamin A Weinberg
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Early Onset ◽  
Older Patients ◽  
Fusobacterium Nucleatum ◽  
Distal Colon ◽  
Gastrointestinal Cancers ◽  
Human Gut ◽  
Colon And Rectal Cancer ◽  
Early Onset Colorectal Cancer

Recently, there has been an unexpected trend toward increased incidence of colorectal cancer in younger individuals, particularly distal colon and rectal cancer in those under age 50. There is evidence to suggest that the human gut microbiome may play a role in carcinogenesis. The microbiome is dynamic and varies with age, geography, ethnicity and diet. Certain bacteria such as Fusobacterium nucleatum have been implicated in the development of colorectal and other gastrointestinal cancers. Recent data suggest that bacteria can alter the inflammatory and immune environment, influencing carcinogenesis, lack of treatment response and prognosis. Studies to date focus on older patients. Because the microbiome varies with age, it could be a potential explanation for the rise in early-onset colorectal cancer.

Su1008 CLINICAL AND PATHOLOGIC CHARACTERISTICS OF EARLY ONSET COLORECTAL CANCER (EOCRC).

2020 ◽  
Vol 158 (6) ◽  
pp. S-496
Author(s):  
Arif A. Arif ◽  
Daljeet Chahal ◽  
Caroline Speers ◽  
Mary A. De Vera ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Early Onset Colorectal Cancer

scholarly journals High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer

2021 ◽  
Author(s):  
Jeong Eun Kim ◽  
Jaeyong Choi ◽  
Chang-Ohk Sung ◽  
Yong Sang Hong ◽  
Sun Young Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Large Scale ◽  
Late Onset ◽  
Age Groups ◽  
The Cancer Genome Atlas ◽  
Whole Genome ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Early Onset Colorectal Cancer

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.

scholarly journals Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Author(s):  
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Early Onset ◽  
Low Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Pathogenic Variants ◽  
Predisposing Genes ◽  
The Mean ◽  
Early Onset Colorectal Cancer

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.

Abstract 838: Sugar-sweetened beverage intake and risk of early-onset colorectal cancer

2021 ◽  
Author(s):  
Jinhee Hur ◽  
Ebunoluwa Otegbeye ◽  
Hee-Kyung Joh ◽  
Katharina Nimptsch ◽  
Kimmie Ng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Sugar Sweetened Beverage ◽  
Sweetened Beverage ◽  
Early Onset Colorectal Cancer
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