Evaluation of genetic polymorphisms and quality of life in women with ovarian carcinoma

Author(s)

Amanda Canato Ferracini

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2021-04-23

Examining board members

Priscila Gava Mazzola; Luiz Carlos Zeferino; Cássia Raquel Teatin Juliato; Daniela Oliveira de Melo; Leonardo Régis Leira Pereira

• Advisor: Sophie Françoise Mauricette Derchain; Priscila Gava Mazzola

Abstract

Introduction: The detection of polymorphisms associated with toxicity and response to chemotherapy, survival, addition with QOL, can contribute to the personalized care of women with ovarian carcinoma undergoing chemotherapy with carboplatin and paclitaxel. Objectives: To evaluate the association between polymorphisms and hematological toxicity and neurotoxicity, response to chemotherapy, survival and QOL in women with ovarian carcinoma. Methods: For this study, women with histological diagnosis of ovarian carcinoma treated at Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Center for Integral Attention to Women's Health (CAISM) of the State University of Campinas (UNICAMP) from January 2014 to July 2019 with follow-up until July 2020. Polymorphisms GSTM1, GSTT1, GSTP1 c.313A>G ABCB1 c.1236C> T, ABCB1 c.3435C>T and ABCB1 c.2677G> T/A were analyzed by the multiplex polymerase chain reaction (PCR) or real-time PCR method. The association between polymorphisms and hematological and neurological toxicity was assessed and variants with p <0.05 were included in multiple regression analyzes. The prospective QOL study used cross-sectional analysis at the beginning of the study and longitudinal analysis from the beginning to the end of 12 months after chemotherapy. QOL was assessed at the beginning of the study, in the 6th cycle and 12 months after chemotherapy using the FACT-O questionnaire. The clinical-pathological characteristics and the chemotherapy regimen were evaluated and tested for associations with QOL measurements. Results: For the evaluation of polymorphisms, 112 women with ovarian carcinoma were included. Women with GSTP1 c.313A> G had an OR = 0.17 (95% CI: 0.04 to 0.69, p = 0.01, dominant model) for anemia and an OR = 0.27 (95% CI: 0.12 to 0.64, p <0.01); and OR = 0.18 (95% CI 0.03 to 0.85, p = 0.03, dominant or recessive model), respectively, for thrombocytopenia. The AG genotype of GSTP1 c.313A> G was associated with a lower risk of dose delay (OR = 0.35, 95% CI: 0.13 to 0.90, p = 0.03). ABCB1 c.1236C> T increased the chance of thrombocytopenia (OR = 3.50 (95% CI 1.12–10.97, p = 0.03), while ABCB1 c.3435C> T increased the risk of neurotoxicity grade 2 and 3 [OR = 3.61 (95% CI: 1.08 to 121.01, p = 0.03)], both in the recessive model (CC + CT vs. TT). Among the 38 women included, 27 (80.1%) answered the QOL questionnaires for one year, with an advanced stage, high levels of CA-125 and neoadjuvant chemotherapy showed worse scores in the initial diagnosis (p <0.05), however, in the longitudinal analysis there was an improvement significant in the mean of the QOL scores during one year in women with ovarian carcinoma (p <0.05). Conclusion: Polymorphism is a potential predictor of hematological toxicity and neurotoxicity. Clinical and pathological characteristics, such as stage, presence of residual disease after surgery and type of chemotherapy, correlated with QOL scores. At the one-year follow-up, women who underwent chemotherapy showed an improvement in QOL (AU)

• FAPESP's process: 16/22335-2 - Evaluation of genetic markers and quality of life in women with ovarian carcinoma
• Grantee: Amanda Canato Ferracini
• Support Opportunities: Scholarships in Brazil - Doctorate