Keywords
brain neoplasm - head trauma - association - risk factors - epidemiology
Introduction
Brain tumors are significant cause of death and disability worldwide with substantial
implications for public health and health care systems. Established risk factors,
such as radiation exposure and genetic predisposition, have been well-documented.[1]
[2]
[3]
[4] However, the potential association between head injuries and brain tumors remains
controversial and has yet to be conclusively established.[1] Despite historical speculation and ongoing debate, no definitive evidence has validated
head injury as a major risk factor for brain tumor development. This knowledge gap
persists, despite the increasing prevalence of traumatic brain injuries globally.[2]
[3]
Several epidemiological studies conducted globally have produced conflicting results.
Some studies suggest a significant association, while others found no substantial
evidence.[4] For instance, a study in Taiwan involving 75,292 patients with a history of head
injury found no association between head injury and meningioma, regardless of age,
gender, or severity.[5] In contrast, another cohort study in Taiwan with a sample size of 30,000 participants
demonstrated a significant correlation between head injury and malignant brain tumors.[6] Similarly, in Sweden, a study of 311,006 hospitalized patients with head injuries
between 1965 and 1994 reported no significant association,[7] whereas a study conducted in Brazil reported a 46% increased risk of brain tumor
development among patients with prior head injuries compared to 36% in a control group.[8] Other studies in France, Germany, and the United States have similarly reported
no substantial link, while research in Denmark suggested a modest increase in brain
tumor risk associated with head injuries.[9]
[10]
[11]
[12] In addition to head injuries, exposure to carcinogenic chemicals such as organic
solvents,[13] lubricating oil,[14] acrylonitrile and vinyl chloride,[15] formaldehyde,[16] polycyclic aromatic hydrocarbons,[17] and phenolic compounds[18] are associated with a higher prevalence of brain tumors. Notably, this increase
was more pronounced among white male workers compared to women and individuals with
darker skin.[19] This suggests that multiple environmental and occupational factors may interplay
with biological mechanisms underlying brain tumor etiology. The variation in findings
regarding head injuries and brain tumors may stem from differences in study design,
population characteristics, control of confounding factors, and latency periods, emphasizing
the need for rigorous, well-designed research to clarify this association.
Afghanistan's high burden of traumatic brain injuries, attributed to prolonged conflict,
frequent accidents, and inadequate infrastructure, necessitates an investigation into
their potential correlation with brain tumor development. This study aims to elucidate
this association within the Afghan population by analyzing variables such as age,
sex, injury frequency, and latency periods. The outcomes will contribute to a deeper
understanding of tumorigenic risk factors and inform evidence-based public health
interventions.
Research Method
Case–control study.
Study Setting
The research was conducted in the Neurosurgery Department of Aliabad University Hospital,
Kabul, Afghanistan.
Sampling Method and Sample Size
Based on international research and using the Epi Info formula, this study included
64 cases and 159 controls. Convenience sampling was used, and the samples have two
types of characteristics:
|
Two-sided confidence level
|
95%
|
Kelsey
|
Fleiss
|
Fleiss W/CC
|
|
Power
|
80%
|
64
|
66
|
72
|
|
Ratio of controls to cases
|
2.5
|
159
|
163
|
179
|
|
Percent of controls exposed
|
25%
|
223
|
229
|
251
|
|
Odd ratio
|
3%
|
|
|
|
|
Percent of cases with exposure
|
47%
|
|
|
|
Inclusion Criteria
Sixty-four patients with a minimum age of 16 diagnosed with brain tumors in their
computed tomography (CT) scan or magnetic resonance imaging (MRI) report were included
as cases, and 159 individuals matched by age and gender, who had undergone brain imaging
(brain CT scan or MRI) for another valid reason but did not have a brain tumor diagnosis
in their brain MRI or CT scan report, were included as controls.
Exclusion Criteria
Patients diagnosed with brain tumors less than 1 year after the head injury or those
suspected of having preexisting tumors before the head injury but undetected due to
the absence of clear symptoms were excluded from the study. Additionally, secondary
brain tumors with primary lesions detected in other body parts were excluded.
Data Collection and Analysis
Data was obtained from hospitalized patients in the Neurosurgery Department of Aliabad
University Hospital between October 2022 and September 2023 using a designed questionnaire.
Brain tumor diagnosis was based on the brain CT scan or brain MRI report. Head injury
inclusion criteria were based on specific characteristics such as loss of consciousness
for more than 10 minutes, repeated dizziness and vomiting, or a history of hospitalization
after head injury [1]. Collected data was analyzed using SPSS 24 software.
Variables
The relationship between brain tumors and previous head injury was studied considering
age, gender, frequency of head injury, and time elapsed since the head injury.
Resources
An adequate number of hospitalized patients with necessary examinations were available
at the Neurosurgery Department of Aliabad University Hospital.
Limitations
In certain cases, distinguishing between primary and secondary brain tumors was challenging.
Such cases were excluded from the study.
Ethical Considerations
This study was approved by the Institutional Review Board of the Kabul University
of Medical Science Research Center. Before the study commenced, the purpose and significance
were explained to each participant. During data collection, informed consent was obtained
from all participants (cases and controls). Participants' involvement was entirely
voluntary.
Results
This study consisted of total 223 participants, of which 64 were diagnosed with brain
tumors (case group) based on the CT scan or MRI reports. The remaining 159 individuals
were not evidenced for brain tumors based on imaging reports (control group). Similarly,
62 individuals had a history of head injury (exposed group), while 161 others had
no history of head injury (unexposed group), as shown in [Table 1]. The participants were categorized into different age groups, and the highest incidence
of brain tumors (71.9%) was observed in the age group of 36 to 65 years as indicated
in [Table 2]. Most participants in the exposed group (77.4%) experienced head injuries only once,
and 80.6% of them had a history of head injury within 1 to 10 years as presented in
[Tables 3] and [4]. In terms of gender distribution, male participants were more prevalent in both
the case group (56.3% male and 43.7% female) and the control group (72.3% male and
27.7% female). The distribution of participants in the study was imbalanced in gender
as shown in [Table 5].
Table 1
Group of case, control, and exposure (head injury)
|
Frequency
|
Percent
|
Cumulative percent
|
|
Group of case: brain tumor
|
64
|
28.7
|
28.7
|
|
Group of control: not brain tumor
|
159
|
71.3
|
100
|
|
Total
|
223
|
100
|
|
|
Exposed to head injury
|
62
|
27.8
|
27.8
|
|
Not exposed to head injury
|
161
|
72.2
|
100
|
|
Total
|
223
|
100
|
|
Table 2
Age of participants in groups—case and control
|
Age groups
|
|
Case: brain tumor
|
Control: no brain tumor
|
Total
|
|
16–25 y
|
Frequency
|
7
|
45
|
52
|
|
Percent
|
10.9
|
0.283
|
23.3
|
|
26–35 y
|
Frequency
|
2
|
21
|
23
|
|
Percent
|
3.1
|
0.132
|
10.3
|
|
36–45 y
|
Frequency
|
14
|
14
|
28
|
|
Percent
|
21.9
|
0.088
|
12.6
|
|
46–55 y
|
Frequency
|
15
|
34
|
49
|
|
Percent
|
23.4
|
0.214
|
22
|
|
56–65 y
|
Frequency
|
17
|
23
|
40
|
|
Percent
|
26.6
|
0.145
|
17.9
|
|
66 y or more
|
Frequency
|
9
|
22
|
31
|
|
Percent
|
14.1
|
0.138
|
13.9
|
|
Total
|
Frequency
|
64
|
159
|
223
|
|
Percent
|
100
|
100
|
100
|
Note: Based on this table, the highest occurrence of brain tumors (71.9%) is found
in the age group of 36 to 65 years.
Table 3
Frequency of exposure (exposed to head injury)
|
Frequency
|
Percent
|
Cumulative percent
|
|
One time
|
48
|
77.4
|
77.4
|
|
More than one time
|
14
|
22.6
|
100
|
|
Total
|
62
|
100
|
|
Note: It can be observed that the majority of participants (77.4%) have experienced
a single occurrence of head injury.
Table 4
Period of exposure (exposed to head injury)
|
Frequency
|
Percent
|
Cumulative percent
|
|
1–5 y
|
27
|
43.5
|
43.5
|
|
6–10 y
|
23
|
37.1
|
80.6
|
|
11–15 y
|
6
|
9.7
|
90.3
|
|
16 y or more
|
6
|
9.7
|
100
|
|
Total
|
62
|
100
|
|
Note: According to the above table, the majority of participants (80.6%) have a history
of head injury in the 1- to 10-year age range.
Table 5
Participants' gender in group of case, control, exposed, and nonexposed
|
|
Female
|
Male
|
Total
|
|
Case: brain tumor
|
Frequency
|
28
|
36
|
64
|
|
Percent
|
43.7
|
56.3
|
100
|
|
Control: no brain tumor
|
Frequency
|
44
|
115
|
159
|
|
Percent
|
27.7
|
72.3
|
100
|
|
Total
|
Frequency
|
72
|
151
|
223
|
|
Percent
|
32.3
|
67.7
|
100
|
|
Pearson chi-square test: Value: 5.395. Degree of freedom: 1. p-Value: 0.02
|
|
Exposed to head injury
|
Frequency
|
21
|
41
|
62
|
|
Percent
|
33.9
|
66.1
|
100
|
|
Not exposed to head injury
|
Frequency
|
51
|
110
|
161
|
|
Percent
|
31.7
|
68.3
|
100
|
|
Total
|
Frequency
|
72
|
151
|
223
|
|
Percent
|
32.3
|
67.7
|
100
|
|
Pearson chi-square test: Value: 0.099. Degree of freedom: 1. p-Value: 0.754
|
Statistical analysis showed a significant association (p-value: 0.002) and an odds ratio of 2.585 (95% confidence interval = 1.388–4.815).
A higher percentage of participants in the case group (42.2%) compared to the control
group (22%) had a history of head injury as shown in [Table 6]. However, regarding the frequency of exposure, 77.8% of the case group and 77.1%
of the control group had experienced head injuries only once as presented in [Table 7].
Table 6
Association of case and control with exposure (head injury)
|
|
Exposed to head injury
|
Not exposed to head injury
|
Odds
|
Total
|
|
Group of case: brain tumor
|
Frequency
|
27
|
37
|
0.73
|
64
|
|
Percent
|
42.2
|
57.8
|
|
100
|
|
Group of control: no brain tumor
|
Frequency
|
35
|
124
|
0.28
|
159
|
|
Percent
|
22
|
78
|
|
100
|
|
Total
|
Frequency
|
62
|
161
|
|
223
|
|
Percent
|
27.8
|
72.2
|
|
100
|
|
Pearson chi-square test: Value: 9.253. Degree of freedom: 1. p-Value: 0.002
|
|
Odds ratio for groups case and control with 95% confident interval: Lower: 1.388.
Upper: 4.815. Value: 2.585
|
Table 7
Association of case and control with frequency of exposure (head injury)
|
|
One time
|
More than one time
|
Total
|
|
Case: brain tumor
|
Frequency
|
21
|
6
|
27
|
|
Percent
|
77.8
|
22.2
|
100
|
|
Control: not brain tumor
|
Frequency
|
27
|
8
|
35
|
|
Percent
|
77.1
|
22.9
|
100
|
|
Total
|
Frequency
|
48
|
14
|
62
|
|
Percent
|
77.4
|
22.6
|
100
|
|
Pearson chi-square test: Value: 0.004. Degree of freedom: 1. p-Value: 0.953
|
Discussion
This study sheds light on the complex and controversial link between head injuries
and brain tumors, contributing to the global debate on this issue. By analyzing data
from 223 participants at the Neurosurgery Department of Ali Abad University Hospital
in Kabul, Afghanistan, we provide fresh insights into a topic of concern. We found
that 71.9% of brain tumor cases occurred in individuals aged 36 to 65 years. These
findings are aligned with the age distribution reported in studies from the United
States and Taiwan.[5]
[10] This raises an important question: Why is this age group disproportionately affected?
Potential explanations for this could be cumulative environmental exposures,[20] age-related declines in immune surveillance,[21] or other factors yet to be investigated. These findings emphasize the need for further
research to investigate the mechanisms of brain tumors in terms of mutations, gene
regulation, and brain tissue dynamics.
Regarding gender, 56.3% of cases were male and 43.7% were female, showing a slight
predominance in males. This minor disparity is consistent with studies from Taiwan
and the United States. However, the difference is not significant enough to draw firm
conclusions. Considering this finding, it appears that males may be slightly more
susceptible to brain tumors without significance, potentially due to environmental
and occupational exposures that increase their risk.[22]
[23] To better understand gender-specific risks, further independent and large-scale
research is needed to clarify this disparity.
Further, we also evaluated whether head injuries could be considered a risk factor
for brain tumors. We observed a notable association: 42% of the participants in the
case group had a history of head trauma. These findings highlight the potential biological
mechanism through which head trauma might influence tumor development by repeatedly
triggering chronic inflammation of the brain, or disruption of blood–brain barrier
integrity, or cellular alterations promoting tumorigenesis.[24]
[25] These findings were consistent with other studies conducted around the world, including
ones from Denmark and Brazil, which reported a similar link between brain tumors and
head trauma. However, large-scale investigations from Sweden, Germany, and the United
States reported no significant correlation between head trauma and tumors. This global
discrepancy raises critical queries: Are certain categories of head injuries more
likely to cause long-term cellular damage, or are certain populations more genetically
prone to develop tumors after trauma?
In our study, most head injury patients (77.4% of the exposed group) experienced a
single head injury, with most injuries occurring 1 to 10 years prior to tumor diagnosis.
Interestingly, there was no significant correlation between head injuries and tumor
development. This suggests that tumor progression may not be primarily influenced
by head injuries. However, is it possible that factors, such as injury type, location,
or severity, play a more substantial role, which are potential directions for future
investigation?
Conclusion
This study demonstrates that there is a significant and positive relationship between
the development of brain tumors and head injuries, and head injuries are considered
a potential contributing factor to the occurrence of brain tumors. However, comparing
the findings of this research with international studies indicates that the relationship
between brain tumors and head injuries is a controversial subject, and it remains
difficult to reject or confirm this association definitively.
