Alarming recent rises in 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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Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer

Diseases of the Colon & Rectum ◽

10.1007/bf02235756 ◽

1998 ◽

Vol 41 (4) ◽

pp. 434-440 ◽

Cited By ~ 26

Author(s):

Ying Yuan ◽

Hye-Jung Han ◽

Shu Zheng ◽

Jae-Gahb Park

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Germline Mutations ◽

Hereditary Nonpolyposis ◽

Early Onset Colorectal Cancer

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

10.1158/1538-7445.am2021-838 ◽

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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Abstract 101: Racial differences in somatic mutations among patients with early-onset colorectal cancer

10.1158/1538-7445.am2021-101 ◽

2021 ◽

Author(s):

Andreana N. Holowatyj ◽

Wanqing Wen ◽

Timothy Gibbs ◽

Kay M. Washington ◽

Paulette D. Chandler ◽

...

Keyword(s):

Colorectal Cancer ◽

Racial Differences ◽

Early Onset ◽

Somatic Mutations ◽

Early Onset Colorectal Cancer

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Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women

Gut ◽

10.1136/gutjnl-2020-323450 ◽

2021 ◽

pp. gutjnl-2020-323450

Author(s):

Jinhee Hur ◽

Ebunoluwa Otegbeye ◽

Hee-Kyung Joh ◽

Katharina Nimptsch ◽

Kimmie Ng ◽

...

Keyword(s):

Colorectal Cancer ◽

Young Adults ◽

Early Onset ◽

Cox Proportional Hazards ◽

Adolescents And Young Adults ◽

Health Study ◽

Birth Cohorts ◽

Sugar Sweetened Beverage ◽

Sweetened Beverage ◽

Early Onset Colorectal Cancer

ObjectiveSugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined.DesignIn the Nurses’ Health Study II (1991–2015), we prospectively investigated the association of SSB intake in adulthood and adolescence with EO-CRC risk among 95 464 women who had reported adulthood beverage intake using validated food frequency questionnaires (FFQs) every 4 years. A subset of 41 272 participants reported beverage intake at age 13–18 years using a validated high school-FFQ in 1998. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% CIs.ResultsWe documented 109 EO-CRC cases. Compared with individuals who consumed <1 serving/week of SSBs in adulthood, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR 2.18; 95% CI 1.10 to 4.35; ptrend=0.02), with a 16% higher risk (RR 1.16; 95% CI 1.00 to 1.36) per serving/day increase. Each serving/day increment of SSB intake at age 13–18 years was associated with a 32% higher risk of EO-CRC (RR 1.32; 95% CI 1.00 to 1.75). Replacing each serving/day of adulthood SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk or total milk was associated with a 17%–36% lower risk of EO-CRC.ConclusionHigher SSB intake in adulthood and adolescence was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among adolescents and young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.

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