Leucemia linfoblástica aguda: avaliação da proporção digital 2D:4D e histórico familiar de fissuras orais

Abstract

Approximately 6,000 cases of acute lymphoblastic leukemia (ALL) are diagnosed every year in the USA, over half of which occur in children and adolescents. . In Brazil, the incidence of LLA is about 40 cases per million people under 15 years of age and the peak incidence between two and five years. Studies associate the occurrence of acute leukemia with in utero exposure to estrogen and the altered expression of Homeobox (HOX) genes. These genes play a significant role in hematopoiesis and leukemogenesis, in addition to acting concomitantly in the differentiation of the fingers in the prenatal period and in craniofacial development, particularly of non-syndromic cleft lip and palate (NSCL/P). The ratio between the index finger and the ring finger, known as the 2D:4D ratio, has been proposed as a marker for HOX activity and prenatal hormone exposure. The present study therefore investigated the relationship between ALL and 2D:4D ratio and history of NSCL/P, to ascertain the existence of a specific digital pattern related to ALL, and to verify if families with individuals diagnosed with leukemia more frequently report a family history of NSCL/P than families without cases of the disease. Two case-control studies were performed. In the first study 129 individuals participated, being 43 patients diagnosed with ALL (case group) and 86 clinically healthy individuals (control group). In the second study, a total of 175 individuals participated, 50 patients with ALL (case group) and 125 clinically healthy individuals (control group). The data collection of the first study involved the measuring of the lengths of the index and ring fingers of the right and left hands using a digital caliper to calculate the 2D:4D ratio, verification of the clinical file and application of questionnaires. In the second study, questionnaires were applied to obtain information about family history of NSCL/P in firstdegree relatives of patients affected by ALL. Statistical analysis was subsequently performed using the SPSS® Version 23.0 for Windows® program, adopting a significance of 5%. To compare the mean 2D:4D ratios between the groups, the student's t-test for independent samples and the Mann-Whitney test were used, while the chi-square test and Fisher's exact test were used in relation to the history of oral clefts. It can be observed that individuals from the case group had very similar mean 2D:4D ratios to the control group (p>0.05), revealing the absence of a specific digital pattern in patients affected by ALL. Individuals diagnosed with leukemia report more frequently a history of oral clefts in families than clinically healthy individuals (chi-square, p = 0.02; Fisher's exact test, p = 0.08) suggesting an association between NSCL/P and ALL. These results suggest that the 2D: 4D ratio is not a marker for this type of cancer in this population and the association between NSCL/P and ALL could indicate mechanisms and participation of common genes, such as HOX family genes.