Abstract A011: Ethnic variation in GSTM1-null polymorphism and its association with cancer risk in the Brazilian population

Abstract Aim: to investigate the frequency of the GSTM1-null genetic polymorphism in the Brazilian population stratified by ethnic background; and to examine its association with cancer and other diseases. This work provides the first systematic synthesis of GSTM1-null frequencies across ethnically diverse Brazilian subpopulations, highlighting significant disparities and potential gene-disease interactions. Methods. A systematic literature review was conducted following the PRISMA-P protocol. Searches were performed in PubMed, LILACS, and Medline (as of December 2024), without restrictions on time or language. Inclusion criteria comprised studies reporting GSTM1-null frequencies stratified by skin color or ethnic background within Brazil. Studies were excluded if deemed methodologically weak based on the STROBE assessment tool. Eligible publications were synthesized to estimate GSTM1-null prevalence by geographic region and self-reported skin color. Associations between the GSTM1-null genotype and disease incidence were examined by ethnic group. Results: Nine cross-sectional studies evaluated individuals categorized as white (n=1,834), brown (n=789), black (n=590), and Amerindian (n=155). The overall GSTM1-null frequency was 44.9%, with whites exhibiting the highest prevalence (51.1%), followed by browns (38.4%), Amerindians (34.8%), and blacks (33.4%). In Southeastern Brazil, whites showed an even higher frequency (53.6%) compared to browns (41.6%) and blacks (29.6%). Cross-sectional studies presented lower GSTM1-null frequencies (44.9%) relative to control groups (48.0%) in case-control studies. Among ten case-control studies analyzed (excluding Amerindians), GSTM1-null genotype was significantly associated with increased cancer risk across multiple groups: black-skinned individuals (OR=2.72; 95% CI: 1.44–5.17), solid tumors in whites (OR=1.55; 1.21–1.98), gastric cancer in whites (OR=4.44; 2.49–7.92), and osteosarcoma in browns (OR=3.50; 1.04–11.77). Additionally, associations were found between GSTM1-null and chronic myeloid leukemia (CML) (OR=0.61; 0.21–0.77), and lung cancer (OR=1.96; 1.01–3.78). Conclusion: These findings underscore the genetic heterogeneity within Brazil’s ethnically diverse population and suggest that GSTM1-null polymorphism may play a significant role in modulating cancer susceptibility across distinct ethnic groups. The study contributes novel, unpublished epidemiological insights and supports the need for further research into gene–environment interactions and disease risk stratification in mixed-ancestry populations. Citation Format: Rafaela S.S. Costa, Ilce Ferreira da. Silva. Ethnic variation in GSTM1-null polymorphism and its association with cancer risk in the Brazilian population [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr A011.