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<p>This study investigates combine effect of low BMI and possible pharmacogenetic influence of <i>ABC</i> gene polymorphisms in treatment responses of BC patients. BMI was analysed prior to commencement of chemotherapy. Clinical response was evaluated by radiological imaging and categorised as per RECISTv.1 criteria. SNPs (C1236T, C3435T, C58626A) in <i>ABCB1</i> and <i>ABCC2</i> gene were selected. 148 patients were analysed using PCR-RFLP. <i>ABCC2</i> (58626AA) was significantly associated with treatment non-responsiveness in all genetic models namely dominant (OR 2.954; [1.442–6.051]; <i>p</i> = <i>0.003</i>), recessive (OR 5.723; [2.48–13.20]; <i>p</i> &lt; <i>0.0001</i>), codominant (χ<sup>2</sup> 21.219; <i>p</i> &lt; <i>0.0001</i>). The proportion of ORR and NRs were significantly different between low (&lt;18.5) and high (≥18.5) BMI classes (OR 16.097; [7.12–36.35]; <i>p</i> &lt; <i>0.0001)</i>. Furthermore, when treatment response was combined with BMI groups, significant associations were observed for C58626A SNP across all genetic models among low BMI group: dominant (OR 3.324; [1.012–10.406]; <i>p</i> = <i>0.041</i>), recessive (OR 7.250; [1.533–34.278]; <i>p</i> = <i>0.012</i>) and codominant (χ<sup>2</sup> 8.657; <i>p</i> = <i>0.013</i>). Both PFS (35.31 months; <i>p</i> = <i>0.005</i>) and OS (39.75 months; <i>p</i> = <i>0.032</i>) were lowered among AA genotype (<i>ABCC2</i>) while the hazard risk of this genotype was further increased in low BMI patients (HR 1.963). 3435CT genotypes in <i>ABCB1</i> gene showed 87% reduction in risk of death (HR 0.13; <i>p</i> = <i>0.025</i>). Low BMI independently and jointly with 58626AA genotype of <i>ABCC2</i> gene was responsible for poor chemotherapy response and survival outcome among AC-T regimen receiving BC patients. Together, this study underscores the importance of genetic counselling and nutritional assessment for favourable treatment outcomes.</p>

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Impact of low BMI and ABCC2 genotype on the clinical response of sequential anthracycline-taxane chemotherapy receiving breast cancer patients: a hospital-based study

  • 期刊论文

  • 发表日期：

    2025年7月16日

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  • Tanuma Mistry,
  • Sanghamitra Sengupta,
  • R. Suresh Kumar,
  • Nisha Thakur,
  • Partha Nath,
  • Neyaz Alam,
  • Vilas D. Nasare

摘要

This study investigates combine effect of low BMI and possible pharmacogenetic influence of ABC gene polymorphisms in treatment responses of BC patients. BMI was analysed prior to commencement of chemotherapy. Clinical response was evaluated by radiological imaging and categorised as per RECISTv.1 criteria. SNPs (C1236T, C3435T, C58626A) in ABCB1 and ABCC2 gene were selected. 148 patients were analysed using PCR-RFLP. ABCC2 (58626AA) was significantly associated with treatment non-responsiveness in all genetic models namely dominant (OR 2.954; [1.442–6.051]; p = 0.003), recessive (OR 5.723; [2.48–13.20]; p < 0.0001), codominant (χ2 21.219; p < 0.0001). The proportion of ORR and NRs were significantly different between low (<18.5) and high (≥18.5) BMI classes (OR 16.097; [7.12–36.35]; p < 0.0001). Furthermore, when treatment response was combined with BMI groups, significant associations were observed for C58626A SNP across all genetic models among low BMI group: dominant (OR 3.324; [1.012–10.406]; p = 0.041), recessive (OR 7.250; [1.533–34.278]; p = 0.012) and codominant (χ2 8.657; p = 0.013). Both PFS (35.31 months; p = 0.005) and OS (39.75 months; p = 0.032) were lowered among AA genotype (ABCC2) while the hazard risk of this genotype was further increased in low BMI patients (HR 1.963). 3435CT genotypes in ABCB1 gene showed 87% reduction in risk of death (HR 0.13; p = 0.025). Low BMI independently and jointly with 58626AA genotype of ABCC2 gene was responsible for poor chemotherapy response and survival outcome among AC-T regimen receiving BC patients. Together, this study underscores the importance of genetic counselling and nutritional assessment for favourable treatment outcomes.