Colorectal cancer (CRC) as one of the most common types of cancer accounting for many mortalities and morbidities worldwide[1]. Many epidemiological studies have estimated the risk of CRC in individuals with a family history of the disease [43]. Several environmental and hereditary factors are known as the risk factors for CRC [44]. In addition, patients with inherited conditions such as, Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and Familial Adenomatous Polyposis (FAP) as well those with a positive family history of CRC in relatives are at a higher risk of developing this condition [45].
Our study revealed a positive association between having positive family history of CRC and the risk of CRC in EMRO region. In a study conducted by a María Del Pilar Ramírez-Díaz, the role of family history was proved as an effective factor in the occurrence of the CRC [46].These results can be related to the common or similar gene sequence in family members that create mechanisms to facilitate the development of the CRC.
There are several well-stablished gene mutations related to CRC cancer development. These mutations can be attributed to different classes of genes[47]. Familial adenomatous polyposis (FAP) is an example of mutation in a Tumor Suppressor gene, APC[48]. Another similar polyposis syndrome related to CRC development is MutY human homologue associated polyposis (MAP) which is caused by a DNA repair gene alteration named MYH[49].
Lynch syndrome also known as hereditary non polyposis colon cancer (HNPCC) is a common predisposing condition of CRC accounting for 2–5% of all cases, is a result of mutation in DNA mismatch repair genes mainly affecting MLH1, MSH2 and MSH6.4[50].
Our subgroup analysis showed that CRC was seen more than 2 times in those whose First-degree relatives were affected. In a meta-analysis conducted by Adam S, people with at least one positive first-degree family history have a higher risk of developing CRC[51]. In a study conducted by Mehraban Far, a positive family history of CRC in first-degree relatives significantly increased risk of CRC [9].
Another result obtained from our meat-analysis was that having a family history of any types of cancer increase the risk of developing CRC. It is of importance that family history of CRC is more likely to cause CRC than having a positive family history of ANY cancer.
These differences can be discussed in several aspects. This could be because some cancers are less likely to be transmitted through inheritance and genetics. Newschaffer et al demonstrated that a positive history of breast cancer did not increase the risk of colorectal cancer and in some sub groups it could be announce as a protective factor[52]. In a recent study by Beebe-Dimmer et al, Positive family history of Prostate cancer did not significantly increase the risk of CRC[53]. In addition, EMRO region people may have a higher susceptibility for CRC than other cancers due to genetical reasons. Environmental status and food habits in this region can resulted in increased risk of CRC than other non-gastrointestinal cancers. However, these results could be due to better CRC screening in this region to identifying Suspicious and possible cases for early treatment.
One of the important points in the final results of our Meta-analysis is the greater effect of having a first-degree family history of ANY cancer group on increasing the risk of CRC. This result is an alarm and a serious warning for people who have this positive family history. Early detection of CRC can significantly prevent the potential risks of mortality and morbidity.