To our knowledge, this is the first study investigating this topic to be conducted in the Levant region, a highly consanguineous region. Given the study was conducted in a countrywide centre for all of the country’s paediatric oncologies in the Paediatrics Hospital, it is likely that this is a representative sample of the prevalence and distribution for paediatric oncologies. It is hard to study socioeconomic status in Syria as the standards are much different than other countries, and it is not socially acceptable to ask about the monthly income .
Jaber et al.  demonstrated that marriages between people of the same kinship were not associated with an increased risk of cancer. However, such marriages have been associated with higher risks of congenital malformations, abortions, stillbirths, recessive gene disorders and other types of morbidity and mortality. Furthermore, Kurita et al.  described 20 families in which familial leukaemia occurred in several siblings, six of the aforementioned families had consanguineous marriages and parents were first cousins (30%), compared to just (4.5%) of families with non-familial leukaemia (p < 0.01).
A study in the UAE with 117 patients, 69 of which were ALL patients, suggested that consanguinity was a protective factor among lymphoma patients. The prevalence of consanguinity was lowered from 50.5% in the general population to 12% in non-Hodgkin lymphoma and 14% in Hodgkin lymphoma, but they also found that leukaemia incidence had increased in consanguineous patients . An earlier study also conducted in the UAE suggested that in consanguinity versus non-consanguinity, the relative risk of leukaemia was 1.66, but it did not specify the type of leukaemia . This was also the case in a Qatari study  conducted on 21 patients with leukaemia where there was a higher prevalence of consanguinity in leukaemia patients without specifying the type.
In this study, the investigators found that fourth-degree consanguinity of the parents was associated with less incidence of ALL among children.
Several studies have reported consanguinity as a causative factor in leukaemia among patients with no apparent recessive gene disorder [11, 23,24,25,26,27]. In addition, it may be that clustering of malignancies in consanguineous families could also be explained by these families being affected by the same environmental factors through living in common residences, contributing to the development of a certain phenotype. However, we found no such an association with family history and ALL.
In addition, the results of our study are consistent with those of Jastaniah and colleagues in their study . This study was conducted on 642 ALL patients, which is the largest and most recent study conducted on the subject. This study showed a lower frequency of ALL in a consanguineous union than in a non-consanguineous union. Therefore, these suggested protective factors being inherited in consanguineous unions rather than permissive factors. However, we excluded inheritable medical conditions that my dispose to having leukaemia such as Fanconi’s anaemia.
Consanguinity raises the rate of homozygosity for the embryo for such oncogenes, which makes it a knock-out embryo. However, at times, this renders the embryo incompatible with life which justifies the increased incidence of foetal wastage from abortions, stillbirths and neonatal deaths [2, 18]. This leads to a decreased frequency in this oncogene which could mask a higher incidence of this tumour in this population . Still, despite the increased foetal mortality from repeated abortions in the offspring in consanguineous marriages, one Bahraini study  showed there might be no significant difference in the rates of foetal wastage than originally identified.
In our study, we showed that fourth-degree consanguinity was associated with less incidence of ALL. However, this may suggest that our sample was affected by Neyman’s bias (survival bias), indicating that children with consanguineous parents died before reaching diagnosis of ALL because they suffered from more aggressive leukaemia. This might be mostly prominent for third-degree consanguinity, not the fourth degree, as closer degree might have had a greater effect that our sample was able to demonstrate this protective factor of consanguinity. Furthermore, we may also speculate that consanguinity carries more risks of other fatal pathologies, causing a higher mortality in children before presenting with leukaemia. These factors could explain the lower incidence of leukaemia among the consanguinity population. Additionally, evolutionary mechanism could contribute to decrease the incidence of hereditary factors that lead to death before reproductive age in a homozygous state, causing these recessive factors to keep running through generations of consanguineous families.
One previous study compared the median age of diagnosis for childhood cancer between consanguineous and non-consanguineous groups and did not identify a significant statistical difference .
We did not find a significant difference in the incidence of ALL between Al-Jazira region and other regions (p > 0.05), suggesting the regional environmental factors had no significant effect on the incidence of leukaemia. This is consistent with the previous study showing no definitive link established between environmental factors and ALL [30, 31]. This is important as Syrians may be frequently predisposed to leukaemogenic substances  which may explain why ALL in Syria has distinguished features such as higher incidence of L2 and T-ALL .
Sample size, not including many centres and not including many confounding factors such as genes, is one of major limitations of this study in addition to the study design. This might affect the generalisability of results, but given that this is one of the few studies in the aspect and due to the very limited resources in Syria, we believe that these results can be used for future studies.