Correlation between Digit Ratio and Incidence of Meningioma and its Clinical Profiles

Background: Proliferation and progression of meningioma were influenced by the balance of estrogen and testosterone. Digit Ratio (DR) was a sign of prenatal exposure to estrogen and testosterone. This study intends to find the relationship between Digit Ratio and meningioma. Aim: To determine the relationship between DR and incidence of Meningioma and its Clinical Profiles (age at the onset, sex, Body Mass Indec (BMI) and histopathology grading) Methods: Analytical observational study was used with case-control design. Case group consisted of patients clinically and histopathologically diagnosed with meningioma (n=25). Patients who were not diagnosed with primary intracranial tumors were included in the control group (n=25). Matched group were conducted. Subjects of this study were patients of RSUP dr Kariadi in the period of January 2016-August 2017. This study was conducted by collecting data consisted of DR, age, sex, BMI, and grading histopathology. Tests used in this study are Chi-Square Test, Mann-Whitney Test and Fishers exact Test. Results: Digit Ratio Mean for right, left and right-left difference were 1.0041; 1.0104 and 0.0357 while for the right and left DR cutoff value 0.993; 0.989. There is a relationship between right and left Digit Ratio and incidence of meningioma (p = 0,000) with OR (Odds Ratio) Right DR = 11.17(CI95% 2,864 – 43,464) and OR left DR = 16,00 (CI95% 4,002 – 63,975). There is a relationship between Right Digit Ratio andBMI case group (p = 0,022). There is no relationship of Digit Ratio and age at onset, gender and histopathology grading (p <0.05). Conclusion: DR is risk factor of Meningioma


Introduction
Meningioma is the primary intracranial benign tumor which is originates from the pia tissue and arachnoid 1 . Meningioma is associated with Body Mass Index (BMI). Meningioma is also associated with high estrogen, progesterone, androgen activity and insulinlike growth factor. 4 Recent studies investigated the impact of prenatal exposure of steroid hormones corelates to the ratio of finger length. Measurement of Digit Ratio (DR), or more precisely the Secondto-Fourth (2D: 4D) ratio, which is a sign of exposure to testosterone and prenatal estrogen and increased sensitivity to testosterone and esterogen 6 . In patients with a history of high estrogen exposure in prenatal, it will increase the sensitivity of some related receptors. Among them are Estrogen Receptor (ER), Progesterone Receptor (PR), and Fibroblast Growth Factor Receptor 1 (FGFR1). 7,8 The relationship between DR to the incidence of Meningioma and its clinical profile were elucidated.

Method
This was an observational analytic study with case-control study design. One group was a group of patients diagnosed with meningioma and one group was people without meningiomas with the same characteristics as the case group selected by matching method. The data taken were the primary data. Consecutive sampling was conducted. The independent variable was DR. The dependent variables were the incidence of meningioma and its clinical profile, which consisted of age at the onset of symptoms, BMI, gender and histopathologic Grading. Ethical Clearance: This study was approved by ethics Committee of Diponegoro University.

Results
The numbers of samples obtained from July to September were 50 samples with 25 samples of meningioma patients included in the case group and 25 samples of patients diagnosed in addition to Meningioma that included inclusion criteria and excluded exclusion criteria  Based on the age characteristic, the case group, the youngest age was 20 years old and the oldest was 62 years with the average age of 43.92 years. In the control group, the youngest age was 20 years old and the oldest was 60 years with the average age of 42.32 years. Thus, it was concluded that case and control groups were matched groups for gender and age.

BMI (case)
Mann-Whitney Grade III 1 (5,9)  In theory, the Digit Ratio value shows the prenatal balance of estrogen and progesterone. In the study, it was concluded that the value of right and left Digit Ratio over the value of cutoff point has a higher risk for experiencing meningioma. It is in line that the Digit Ratio value of more than 1 has a higher prenatal estrogen tendency 38 . Whereas in Meningioma, one of the tumor developments is affected by the balance of reproductive hormones, especially high estrogen 39 . Furthermore, in histopathology review, ER + was obtained in patients with Meningioma. This is associated with a Digit Ratio value greater than 1 and above the cutoff point in this study. 16 In the whole group and control group, there was no significant correlation between Right Digit Ratio to BMI p = 0,619 (p> 0,05  40 . The process of formation and growth of the tumor mass is influenced by estrogenic circulation. In patients with a Digit Ratio greater than 1 have a predisposition for dominant prenatal estrogen, and this is associated with the incidence of meningioma. 31 In this study, weight and height measurements were taken when patients were still able to be cooperated, in patients with impaired awareness and limb disability, weight and height data were taken at the time of admission to the hospital seen from medical records. Then, the difference in measuring instruments used (the scales on the wards, the scales at the emergency room, and the scales brought by the researcher for home visits) is also one of the limitations of this study. This study, only explaining the presence or absence of relationships and the magnitude of risk factors, but cannot explain why it can affect each other. It is hoped that further research with regard to ER histopathology of meningioma can be a bridge connecting Digit Ratio relation to meningioma occurrence. This study also used consecutive sampling due to the small prevalence of cases and limited time of research. In subsequent research, it is desirable to use sampling methods that better represent actual populations.

Conclusions and suggestions Conclusion
Based on the results of research that has been discussed, it was found that the DR is a risk factor of Meningioma.

Suggestion
Based on the conclusions of this study, the researcher gives suggestions for the next research, it is expected to improve the short comings of this study, among others, increasing the number of samples and length of research. Then, in this study, only explains the relationship without explaining the cause of each variable. The next researcher is expected to