Association between Brain Tumors and Head Injury: A Hospital-Based Case–Control Study in Afghanistan

Abstract

Objectives

Brain tumors pose a significant global health challenge, contributing to both mortality and disability. While various risk factors have been proposed, the association between head injuries and brain tumor development remains debated. Understanding this link is particularly crucial in resource-limited regions like Afghanistan. This study aims to investigate the potential correlation between head injuries and brain tumor development in the Afghan population.

Materials and Methods

This case–control study was conducted at Ali Abad University Hospital in Kabul from October 2022 to September 2023. Data were collected from 64 patients diagnosed with brain tumors (cases) and 159 matched controls without tumors. Patient demographics and history of head injuries were recorded and analyzed.

Results

The association between head injury and brain tumor incidence was assessed using the chi-square test and logistic regression. An odds ratio (OR) with a 95% confidence interval (CI) was calculated to determine the strength of the association, with statistical significance set at p < 0.05. A history of head injury was reported in 42.2% of brain tumor cases, compared to 22% in the control group (p = 0.002). Individuals with a history of head injury had significantly higher odds of developing a brain tumor (OR = 2.585; 95% CI = 1.388–4.815). Most brain tumor cases (71.9%) were aged 36 to 65 years, with a gender distribution of 56.3% male and 43.7% female. In contrast, the control group had a higher proportion of males (72.3%).

Conclusion

This study suggests a significant correlation between head injuries and brain tumor development, aligning with findings from global research on this debated relationship. Further large-scale studies across Afghanistan are needed to validate these findings and provide deeper insights into the potential risks associated with head injuries and brain tumor development.

 

MissingLinkText

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.

 

MissingLinkText

Study Setting

The research was conducted in the Neurosurgery Department of Aliabad University Hospital, Kabul, Afghanistan.

 

MissingLinkText

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%

 

MissingLinkText

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.

 

MissingLinkText

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.

 

MissingLinkText

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.

 

MissingLinkText

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.

 

MissingLinkText

Resources

An adequate number of hospitalized patients with necessary examinations were available at the Neurosurgery Department of Aliabad University Hospital.

 

MissingLinkText

Limitations

In certain cases, distinguishing between primary and secondary brain tumors was challenging. Such cases were excluded from the study.

 

MissingLinkText

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.

 

MissingLinkText

 

MissingLinkText

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

 

MissingLinkText

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?

 

MissingLinkText

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.

 

MissingLinkText

 

MissingLinkText

Conflict of Interest

None declared.

Note

A recommendation for a comprehensive and national cohort study conducted at a larger scale throughout Afghanistan, to reach a more reliable and generalizable conclusion at the national level. Considering that this research was designed as a case–control study in the most important national center for brain tumor treatment in Afghanistan, “Ali Abad University Hospital - Kabul City,” and with an adequate number of case and control samples, this study represents the first nationwide study and its results are highly credible. This research was limited to a sample collected within 1 year from a single neurosurgery center. All information presented in the manuscript has been rigorously based on empirical data and supported by robust academic evidence. Data has been clearly and transparently represented, maintaining integrity and openness throughout the research process. Every effort was undertaken to provide a comprehensive and accurate account, with full transparency to allow for scrutiny and verification of the findings by the academic community.

• References

• 1 Annegers JF, Laws Jr ER, Kurland LT, Grabow JD. Head trauma and subsequent brain tumors. Neurosurgery 1979; 4 (03) 203-206
• 2 Pavlovic D, Pekic S, Stojanovic M, Popovic V. Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary 2019; 22 (03) 270-282
• 3 Barnholtz-Sloan JS, Ostrom QT, Cote D. Epidemiology of brain tumors. Neurol Clin 2018; 36 (03) 395-419
• 4 Rasheed S, Rehman K, Akash MSH. An insight into the risk factors of brain tumors and their therapeutic interventions. Biomed Pharmacother 2021; 143: 112119
• 5 Kuan AS, Chen YT, Teng CJ, Wang SJ, Chen MT. Risk of meningioma in patients with head injury: a nationwide population-based study. J Chin Med Assoc 2014; 77 (09) 457-462
• 6 Chen Y-H, Keller JJ, Kang J-H, Lin H-C. Association between traumatic brain injury and the subsequent risk of brain cancer. J Neurotrauma 2012; 29 (07) 1328-1333
• 7 Nygren C, Adami J, Ye W. et al. Primary brain tumors following traumatic brain injury–a population-based cohort study in Sweden. Cancer Causes Control 2001; 12 (08) 733-737
• 8 Monteiro GTR, Pereira RA, Koifman RJ, Koifman S. Head injury and brain tumours in adults: a case-control study in Rio de Janeiro, Brazil. Eur J Cancer 2006; 42 (07) 917-921
• 9 Cabaniols C, Giorgi R, Chinot O. et al. Links between private habits, psychological stress and brain cancer: a case-control pilot study in France. J Neurooncol 2011; 103 (02) 307-316
• 10 Carpenter AV, Flanders WD, Frome EL, Cole P, Fry SA. Brain cancer and nonoccupational risk factors: a case-control study among workers at two nuclear facilities. Am J Public Health 1987; 77 (09) 1180-1182
• 11 Schlehofer B, Blettner M, Becker N, Martinsohn C, Wahrendorf J. Medical risk factors and the development of brain tumors. Cancer 1992; 69 (10) 2541-2547
• 12 Inskip PD, Mellemkjaer L, Gridley G, Olsen JH. Incidence of intracranial tumors following hospitalization for head injuries (Denmark). Cancer Causes Control 1998; 9 (01) 109-116
• 13 Walter J, Schwarting J, Plesnila N, Terpolilli NA. Influence of organic solvents on secondary brain damage after experimental traumatic brain injury. Neurotrauma Rep 2020; 1 (01) 148-156
• 14 Thomas TL, Waxweiler RJ, Crandall MS. et al. Brain cancer among OCAW members in three Texas oil refineries. Ann N Y Acad Sci 1982; 381 (01) 120-129
• 15 Kielhorn J, Melber C, Wahnschaffe U, Aitio A, Mangelsdorf I. Vinyl chloride: still a cause for concern. Environ Health Perspect 2000; 108 (07) 579-588
• 16 Tulpule K, Dringen R. Formaldehyde in brain: an overlooked player in neurodegeneration?. J Neurochem 2013; 127 (01) 7-21
• 17 De Roos AJ, Rothman N, Brown M. et al. Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors. Neuro-oncol 2006; 8 (02) 145-155
• 18 Perrone L, Sampaolo S, Melone MAB. Bioactive phenolic compounds in the modulation of central and peripheral nervous system cancers: facts and misdeeds. Cancers (Basel) 2020; 12 (02) 454
• 19 Thomas TL, Waxweiler RJ. Brain tumors and occupational risk factors: a review. Scand J Work Environ Health 1986; •••: 1-15
• 20 Ostrom QT, Francis SS, Barnholtz-Sloan JS. Epidemiology of brain and other CNS tumors. Curr Neurol Neurosci Rep 2021; 21 (12) 68
• 21 Finger CE, Moreno-Gonzalez I, Gutierrez A, Moruno-Manchon JF, McCullough LD. Age-related immune alterations and cerebrovascular inflammation. Mol Psychiatry 2022; 27 (02) 803-818
• 22 Khazaei Z, Goodarzi E, Borhaninejad V. et al. The association between incidence and mortality of brain cancer and human development index (HDI): an ecological study. BMC Public Health 2020; 20 (01) 1696
• 23 Connelly JM, Malkin MG. Environmental risk factors for brain tumors. Curr Neurol Neurosci Rep 2007; 7 (03) 208-214
• 24 Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG. Does neuroinflammation fan the flame in neurodegenerative diseases?. Mol Neurodegener 2009; 4: 47
• 25 Xiong Y, Mahmood A, Chopp M. Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities. Chin J Traumatol 2018; 21 (03) 137-151

Publication History

Article published online:
10 March 2025