Associations of body mass index at different ages with early-onset colorectal cancer

It has been acknowledged that excess body weight increases the risk of colorectal cancer (CRC); however, there is little evidence on the impact of body mass index (BMI) on CRC patients’ long-term oncologic results in Asian populations. We studied the influence of BMI on overall survival (OS), disease-free survival (DFS), and CRC-specific survival rates in CRC patients from the administrative claims datasets of Taiwan using the Kaplan–Meier survival curves and the log-rank test to estimate the statistical differences among BMI groups. Underweight patients (<18.50 kg/m2) presented higher mortality (56.40%) and recurrence (5.34%) rates. Besides this, they had worse OS (aHR:1.61; 95% CI: 1.53–1.70; p-value: < 0.0001) and CRC-specific survival (aHR:1.52; 95% CI: 1.43–1.62; p-value: < 0.0001) rates compared with those of normal weight patients (18.50–24.99 kg/m2). On the contrary, CRC patients belonging to the overweight (25.00–29.99 kg/m2), class I obesity (30.00–34.99 kg/m2), and class II obesity (≥35.00 kg/m2) categories had better OS, DFS, and CRC-specific survival rates in the analysis than the patients in the normal weight category. Overweight patients consistently had the lowest mortality rate after a CRC diagnosis. The associations with being underweight may reflect a reverse causation. CRC patients should maintain a long-term healthy body weight.

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

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00583-1 ◽

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.

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

Cancers ◽

10.3390/cancers13153857 ◽

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.

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