Colorectal Cancer in North-Eastern Iran: a retrospective, comparative study of early-onset and late-onset cases based on data from the Iranian hereditary colorectal cancer registry

Abstract Background The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. Methods This retrospective study, carried out over a three-year follow-up period (2014–2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years. Results From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS. Conclusion The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.

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Colorectal Cancer in Iran: A Retrospective, Comparative Study of Early-onset and Late-onset Cases in north-eastern Iran based on the Iranian Hereditary Colorectal Cancer Registry

10.21203/rs.3.rs-137344/v1 ◽

2021 ◽

Author(s):

Benyamin Hoseini ◽

Zahra Rahmatinejad ◽

Ladan Goshayeshi ◽

Robert Bergquist ◽

Fatemeh Rahmatinejad ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Young Patients ◽

City Hospital ◽

Genetic Characteristics ◽

Eastern Iran ◽

North Eastern ◽

Tumour Location

Abstract Background: Generally, the incidence rate of colorectal cancer (CRC) is increasing among young patients (aged <49 years), while the reasons for the rising incidence are unclear. Indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent manner. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and pathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. Methods: This retrospective study was carried out over a three-year follow-up period (2014-2017) and included 562 CRC patients in three Mashhad City hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and familial features together with information on the presence of genetic mismatch repair-deficiency in relation to final patient status (surviving versus deceased cases). Analyses using R studio software were performed on early-onset CRC (n=222) and late-onset CRC (n=340) groups produced by division at the age of 50 years. Results: From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC compared to men (56% vs. 44 %) , while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, while it was 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal, and proximal), the frequencies were 61%, 28% and 11%, respectively, but the variation did not reach statically significance. There was a dramatic difference with regard to the history of CRC in second-degree relatives (SDR) and that of the combination of first-degree relatives and SDR (p=0.001 and p=0.03, respectively). Expression of the MLH1 and PMS2 genes were significantly different between survivors and deceased, however this finding was not observed with regard to the MSH6 and the MSH2 genes. Conclusion: The variation of demographic, pathological and genetic characteristics of CRC between early-onset and late-onset cancers of this kind emphasizes the need for a well-defined algorithm to identify high-risk patients.

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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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Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

Molecular Cancer ◽

10.1186/1476-4598-9-100 ◽

2010 ◽

Vol 9 (1) ◽

pp. 100 ◽

Cited By ~ 54

Author(s):

Marianne Berg ◽

Trude H Agesen ◽

Espen Thiis-Evensen ◽

INFAC-study group [infac] ◽

Marianne A Merok ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

High Resolution ◽

Gene Expression Data ◽

Early Onset ◽

Late Onset ◽

Expression Data ◽

Susceptibility Loci ◽

Genome Profiles

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Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20040968 ◽

2019 ◽

Vol 20 (4) ◽

pp. 968 ◽

Cited By ~ 6

Author(s):

Edurne Álvaro ◽

Juana M. Cano ◽

Juan L. García ◽

Lorena Brandáriz ◽

Susana Olmedillas-López ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Cpg Island ◽

Low Frequency ◽

Tumor Location ◽

Molecular Characteristics ◽

Braf Mutations ◽

Rectal Cancers

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.

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Global Transcriptome Differences Between Early-Onset and Late-Onset Colorectal Cancer

The American Journal of Gastroenterology ◽

10.14309/00000434-201510001-01399 ◽

2015 ◽

Vol 110 ◽

pp. S604-S605

Author(s):

Xi Emily. Zheng ◽

Manish A. Shah ◽

Xiaoping Zou ◽

Levi Waldron

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Late Onset ◽

Global Transcriptome

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Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa164 ◽

2020 ◽

Author(s):

Xiaobin Zheng ◽

Jinhee Hur ◽

Long H Nguyen ◽

Jie Liu ◽

Mingyang Song ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Diet Quality ◽

Early Onset ◽

Strong Support ◽

Healthy Eating Index ◽

Malignant Potential ◽

Poor Diet ◽

Increased Risk

Abstract Background The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed under age 50 has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. Methods In a prospective cohort study (Nurses’ Health Study II), we evaluated two empirical dietary patterns (Western and prudent) and three recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous/villous histology, high-grade dysplasia, or ≥ 3 adenomas), among 29474 women with ≥1 lower endoscopy before age 50 (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We documented 1157 early-onset adenomas with 375 of high-risk. Western diet was positively, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (OR [95% CI] for the highest versus lowest quintile: Western = 1.67 [1.18 to 2.37]; prudent = 0.69 [0.48 to 0.98]; DASH = 0.65 [0.45 to 0.93]; AMED = 0.55 [0.38 to 0.79]; AHEI-2010 = 0.71 [0.51 to 1.01]; all P trend≤.03), driven by those identified in the distal colon and rectum (all P trend≤.04 except AMED: Ptrend=.14). Conclusion Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

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Su1662 – Time to Diagnosis of Early-Onset Vs. “Late-Onset” Colorectal Cancer: is There a Difference?

Gastroenterology ◽

10.1016/s0016-5085(19)38400-8 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-602

Author(s):

Thomas F. Imperiale ◽

Laura Myers ◽

Kayla L. Chin ◽

Carrie J. Ballard ◽

Jessica Coffing ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Late Onset ◽

Time To Diagnosis

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Incident Crohn’s Disease as a Risk Factor for Colorectal Cancer in the First 10 Years after Diagnosis: A Nationwide Population-Based Study

Journal of Clinical Medicine ◽

10.3390/jcm10204663 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4663

Author(s):

Hyunil Kim ◽

Ji Hoon Kim ◽

Jung Kuk Lee ◽

Dae Ryong Kang ◽

Su Young Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Early Onset ◽

Late Onset ◽

Age Groups ◽

Population Based ◽

Hazard Ratios ◽

Increased Risk ◽

Cox Proportional Hazard Regression

We investigated the risk of colorectal cancer (CRC) in patients with Crohn’s disease (CD) using the claims data of the Korean National Health Insurance during 2006–2015. The data of 13,739 and 40,495 individuals with and without CD, respectively, were analyzed. Hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression tests. CRC developed in 25 patients (0.18%) and 42 patients (0.1%) of the CD and non-CD groups, respectively. The HR of CRC in the CD group was 2.07 (95% confidence interval (CI), 1.25–3.41). The HRs of CRC among men and women were 2.02 (95% CI 1.06–3.87) and 2.10 (95% CI, 0.96–4.62), respectively. The HRs of CRC in the age groups 0–19, 20–39, 40–59, and ≥60 years were 0.07, 4.86, 2.32, and 0.66, respectively. The HR of patients with late-onset CD (≥40 years) was significantly higher than that of those with early-onset CD (<40 years). CD patients were highly likely to develop CRC. Early-onset CD patients were significantly associated with an increased risk of CRC than matched individuals without CD. However, among CD patients, late-onset CD was significantly associated with an increased risk of CRC.

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Risk factors and clinical characteristics of early-onset colorectal cancer vs. late-onset colorectal cancer

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0000000000002000 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Milena Di Leo ◽

Raffaella A. Zuppardo ◽

Marta Puzzono ◽

Ilaria Ditonno ◽

Alessandro Mannucci ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Early Onset ◽

Clinical Characteristics ◽

Late Onset ◽

Early Onset Colorectal Cancer

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Diagnostic Performance of First Trimester Screening of Preeclampsia Based on Uterine Artery Pulsatility Index and Maternal Risk Factors in Routine Clinical Use

Diagnostics ◽

10.3390/diagnostics10040182 ◽

2020 ◽

Vol 10 (4) ◽

pp. 182

Author(s):

Max Mönckeberg ◽

Valentina Arias ◽

Rosario Fuenzalida ◽

Santiago Álvarez ◽

Victoria Toro ◽

...

Keyword(s):

High Risk ◽

Early Onset ◽

Diagnostic Performance ◽

Uterine Artery ◽

Late Onset ◽

First Trimester ◽

Maternal Risk ◽

Predictive Algorithm ◽

First Trimester Of Pregnancy ◽

Early Onset Preeclampsia

Preeclampsia is a pregnancy-specific disorder defined by new onset of hypertension and proteinuria after 20 weeks of gestation. The early detection of patients at risk of developing preeclampsia is crucial, however, predictive models are still controversial. We aim to evaluate the diagnostic performance of a predictive algorithm in the first trimester of pregnancy, in order to identify patients that will subsequently develop preeclampsia, and to study the effect of aspirin on reducing the rate of this complication in patients classified as high risk by this algorithm. A retrospective cohort including 1132 patients attending prenatal care at Clínica Dávila in Santiago, Chile, was conceived. The risk of developing preeclampsia (early and late onset) was calculated using algorithms previously described by Plasencia et al. Patients classified as high risk, in the first trimester of pregnancy, by these algorithms, were candidates to receive 100 mg/daily aspirin as prophylaxis at the discretion of the attending physician. The overall incidence of preeclampsia in this cohort was 3.5% (40/1132), and the model for early onset preeclampsia prediction detected 33% of patients with early onset preeclampsia. Among the 105 patients considered at high risk of developing preeclampsia, 56 received aspirin and 49 patients did not. Among those who received aspirin, 12% (7/56) developed preeclampsia, which is equal to the rate of preeclampsia (12% (6/49)) of those who did not receive this medication. Therefore, the diagnostic performance of an algorithm combining uterine artery Doppler and maternal factors in the first trimester predicted only one third of patients that developed preeclampsia. Among those considered at high risk for developing the disease using this algorithm, aspirin did not change the incidence of preeclampsia, however, this could be due either to the small study sample size or the type of the study, a retrospective, non-interventional cohort study.

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