Colorectal Cancer

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WHO-ICD-10 version:2010

Neoplasms

Malignant neoplasms

OMIM Number

114500

Mode of Inheritance

Autosomal dominant, Somatic mutations

Gene Map Locus

1p13.2, 1p36.13,2p25.1,3p22.1, 3q26.3,4p16.3, 4q31.3 ,5q22.2,7q11.23 ,8p22.1, 8q22.1 ,9q32-q33,11p11.2, 11q13.3,14q24.3, 14q32.33,15q15.1,17p11.2, 17p13.1, 17q24.1,20q11.23, 20q13.2,22q13.2

Description

Colorectal cancer is a heterogeneous disease that is common in both men and women. In addition to lifestyle and environmental risk factors, gene defects can contribute to an inherited predisposition to CRC. CRC is caused by changes in different molecular pathogenic pathways, such as chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Chromosome instability is the most common alteration and is present in almost 85% of all cases. [From OMIM]

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
114500.G.1.1Lebanon Neoplasm of the large intestineNM_004612.4:c.51_78=, NM_004612.4:c.52_54GCG[6]HeterozygousIbrahim et al. 2014 Study with 96 colore...
613659.G.1.2LebanonUnknown Neoplasm of the large intestineCYP2E1*6 Allele NM_000773.4:c.967+1143T>A, CYP1A1*2A Allele NG_061374.1:g.11229T>CHeterozygousDarazy et al. 2011 57 patients with col...

Other Reports

Jordan

Arafa et al. (2011) conducted a study among first degree relatives of colorectal cancer cases for early detection and screening for colon cancer in AL-Bashir hospital in Jordan.  All individuals included in the study were above 40 years of age.  Among 3574 subjects, 153 (4.3%) individuals were complaining of signs and symptoms suggestive of CRC.  Of the latter, 58 (37.9%) did not accept colonoscopy examination.  Of the 95 individuals who underwent colonoscopy, 2 were confirmed of having CRC.  The 2 cases were referred to the hospital for treatment and follow up.

Mahasneh et al. (2012) conducted a study in 49 (5 women and 44 men) lung cancer patients, 54 (26 women and 28 men) colorectal cancer patients and 99 (7 women and 92 men) cancer-free controls. Using PCR-RFLP, the polymorphisms of NAT2 gene were screened. Five types of the alleles were found, the wild type WT (NAT2*4) allele and the M1 (NAT2*5A), M2 (NAT2*6A), M3 (NAT2*7), and the M4 (NAT2*14A) polymorphisms caused by point mutations in the NAT2 gene. The M2 polymorphism was apparent in the lung and colorectal cancer patients.

Kuwait

Behbehani et al. (1995) studied the correlation between survival and serum Carcino-Embryonic Antigen (CEA) levels in 464 colorectal carcinoma patients. Overall 5-year survival rate was calculated at 59.2%, and the survival rate decreased with increasing CEA levels. The post-operative longitudinal pattern of CEA was also noted. Patients with an increasing pattern were found to have the least 5-year survival rate (30.1%). Multivariate regression analysis revealed the stage of the disease, initially elevated serum CEA, age over 60-years, location of cancer in the rectum, and a pattern of CEA levels increasing after surgery to be independent ominous prognostic indicators.

Khoursheed et al. (2002) studied normal and malignant tissue samples from patients who underwent resection of colorectal cancer in a Kuwaiti hospital between 1998 and 2000, with an aim to determine the expression of CD44 antigen in these tissues. In all, there were 49 patients (22 females and 27 males; mean age: 55.7 years). All tumors were adenocarcinomas. In 12 patients, the tumor was in the rectum, while in the remaining it was colonic. Immunohistochemical studies using monoclonal antibodies against CD44 showed positive staining in 41% of malignant epithelial tissue as compared to 10% of normal tissue, while both normal and malignant cells showed high staining in the stromal cells. No correlation was found between the level of CD44 expression and clinical parameters, such as Dukes classification, degree of histological differentiation, sex, and size of tumor. However, a significantly higher expression of CD44 was noticed in the epithelium of rectal cancer compared to colonic cancer.

Al Mulla et al. (2006) reported the first attempt to study early-stage colorectal cancer at the genomic level using genome-wide scanning DNA methodologies. Primary tumors from 70 patients with early-stage forms of sporadic colorectal cancers were examined. In all causes there was no evidence of lymph node or distance metastasis at the time of surgery. Microsatellite analysis showed that most of cancers analyzed were microsatellite stable. Metaphase-based comparative genomic hybridization (CGH) was used to seek genomic markers capable of predicting metastatic behavior in this cohort of microsatellite-stable early-stage CRC and the aberrations confirmed independently in a subset of patients using microarray-based CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Al Mulla et al. (2006) found that this study demonstrated a relationship between loss of chromosomes 1p, 4, 5q, 8p, 9p, 14q, 18p and gain of chromosomes 1q, 8q and 13q and metastatic recurrence of early-staged CRC after surgical intervention. It was found that metastatic primary tumors exhibited more complex genomic aberrations than non-metastatic primary tumors, loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis and loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumors with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumors with loss of any one of the two chromosomes. Al Mulla et al. (2006) concluded that genetic profiling of primary tumors of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Thus, they suggested that the molecular genetic features of primary tumors should be considered in the mainstream management of patients with this specific stage of the disease.

Lebanon

Ibrahim et al (2018) studied the molecular characteristics of 645 Lebanese colorectal cancer patients, and found mutations in RAS (38.5%), BRAF (12.9%), and PI3KCA (11.1%) genes.

Qatar

Rasul et al. (2001) undertook a retrospective study of patients diagnosed with colorectal cancer in Qatar between the years 1994 and 1998. A total of 75 Qatari patients (26 males, 19 females; mean age: 57.1 years) were diagnosed with colorectal cancer in this period. The average annual incidence of this condition was calculated as 7.5 per 100,000 individuals. This is significantly lower than reports from other countries, probably due to an increased dietary intake of fruits and vegetables, and reduced incidence of alcohol consumption and smoking among the Qataris. The age range of 60-70 years had the most number of patients (12). However, unlike other reports from Western countries, the number of patients below the age of 40 was fairly high in this study (9). Rasul et al. (2001) attributed this to the higher percentage of younger people in the Qatari population, necessitating that future screening programs be targeted at this group. Most patients were in stage Duke B16 and C16. Histopahologically, adenocarcinoma (14) was the most common type. The most common site of tumor presentations were the descending and sigmoid colon (56%). Follow-up study revealed that the 5-year survival rate was fairly good at 55%.

Bener et al. (2008) retrospectively studied the Qatar National Cancer Registry to assess the trend in various cancer incidences in Qatar. Colon and Rectal cancers were diagnosed in 23 and 10 Qatari patients between 1991 and 1996, 38 and 7 Qataris between 1997 and 2001 and in 43 and 19 Qataris between 2002 and 2006, respectively.

Saudi Arabia

Isbister (1992) conducted a study to compare data pertaining colorectal cancer collected from tumour registry at King Faisal Specialist Hospital & Research Centre and New Zealand, a 'high risk' country for colorectal cancer. The Saudi cancer registry yielded a total of 622 colorectal cancer cases (321 males, 207 females; 538 Saudi nationals) registered between 1975 and 1989, which were compared with 2,420 patients with colorectal adenocarcinoma registered in the New Zealand registry between 1968 and 1970. Of the 622 patients from Saudi Arabia, 119 were below the age of 40-years. In addition, the less well-differentiated tumours, such as mucinous and signet ring carcinomas, tended to be more common among the younger patients. This was different from the observation in the New Zealand data, where these aggressive cancers were found more in older patients, prompting Isbister (1992) to suggest that colorectal cancer in countries with lower incidence might be more aggressive that those in countries with higher incidence.

Al-Ahwal and Al-Ghamdi (2006) studied the clinical features and risk factors associated with colorectal cancer in Saudi Arabia. Over a 10-year period (1993-2002), a total of 33 Saudi patients were diagnosed with colorectal cancer in the Western Region of the country. The number of males was higher than females in this patient population. Analysis of the risk factors showed that among the Saudi patients, the most common risk factors for the development of CRC were use of non-steroidal anti-inflammatory drugs (93.9%), and high fat intake (72.7%), obesity(30.3%), and rarely, familial factors (15.2%), polyps (12.1%), and inflammatory bowel disease (6.1%). Of the five Saudis with familial risk factors, three had a positive family history for colorectal cancer; one had a family history of ovarian and uterine cancer, while the fifth had a family history of adenomatus polyposis syndrome.

Ibrahim et al. (2008) designed a model to assess the future burden of colorectal cancer in Saudi Arabia. ASRs for CRC in the country taken from the National Cancer Registry database showed a progressively rising rate for both males and females (3.38 in 1994 versus 5.84 in 2003). Ibrahim et al. (2008) attributed this to the increase in exposure to dietary risk factors, lack of nationwide screening, and the increase in the age of the population. The incidence of and mortality due to CRC in males was found to be equal to that in less developed countries, however, it was higher in the case of females. Ibrahim et al. (2008) tried to predict the future CRC burden in the country using an estimate of an increase of 0 to 2% in ASR. Even with this conservative estimate, they predicted an increase of fourfold in the incidence rate of CRC by 2030, and recommended that health authorities ready themselves to face this expected surge.

A study by Abubaker et al. (2008) assessed the PIK3CA mutational status in a series of 410 Middle Eastern colorectal cancer (CRC) patients in Saudi Arabia. The study detected PIK3CA mutations in 12% of the CRC cohort. This highlighted the high prevalence of genetic alterations in PI3K/AKT pathway in the group of patients with CRC. Moreover, there was a strong association between PIK3CA mutations and microsatellite instability (P=0.0046). On the other hand, the gene PTEN was inactivated in 66% of the CRC group, and this inactivation was more frequent in microsatellite stable CRC cases (P=0.043). These findings indicate possible involvement of PIK3CA mutations in the development/progression of microsatellite instable colorectal cancer.

Khabaz et al. (2016) carried out a study to determine if GSTM1 gene polymorphism increases the risk of developing colorectal cancer in Saudi patients.  Tissue samples were obtained from 83 colorectal cancer affected individuals and 35 unaffected controls.  All patients with a family history of colorectal cancer were excluded from this study.  The mean age of the cancer patients was 57.8 years and the average tumor size was 5 cm.  By carrying out PCR and gene sequencing assays it was found that 83% of the colorectal cancer cases carried the null genotype (GSTM1*0/*0) while the remaining 17% were either the GSTM1wt/wt or GSTM1wt/*0 genotypes.  In comparison, only 65% of the controls carried the null genotype.  The authors found a statistically significant association between the GSTM1 null genotype and the risk of colorectal cancer [p=0.03706, OR=2.57 (1.04-6.35)]. 

Semlali et al. (2016) conducted a study to determine the association between TLR4 polymorphisms and the risk of developing colon cancer in Saudi Arab individuals.  A total of 115 colon cancer affected patients and 102 healthy controls were recruited for the study.  An analysis revealed that the expression of TLR4 was significantly higher in colon cancer tissues than normal tissues (p<0.001).  The expression levels of cytokines (IL-1b1, IL-6, IL-8, IL-17) were also significantly higher in colon cancer tissues.  The variant rs10759931 showed a strong association with colon cancer irrespective of gender or age [p<0.00001, OR=0.086 (0.04-0.18)]. The polymorphism rs2770150 (was associated with an increased risk of colon cancer in women over the age of 50 [p<0.00084, OR=0.188 (0.074-0.48)] and was linked to the post-menopausal decrease in levels of female sex hormones. 

Syria

The Centre for Arab Genomic Studies Work Group (2004) conducted a retrospective study for cancers described at AlQassimi Hospital in Sharjah from years 2002-2004. Only one case of colon cancer was described in year 2003 in a 50-year-old male from Syria. No further details could be obtained.

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