Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer

X.-L. Zhu, X. Han, X.-F. Xin, H.-J. Song, H. Guo

Department of Anesthesiology, First Affiliated Hospital of Jiamusi University, Jiamusi, China. jmsdxhx@163.com

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• Pharmacology

OBJECTIVE: To investigate the correlations of analgesic dosage of morphine with solute carrier family 6 member 4 (SLC6A4) gene polymorphisms in patients with lung cancer.

PATIENTS AND METHODS: A total of 200 lung cancer patients without cancer pain were selected as painless group, and another 200 lung cancer patients with cancer pain as cancer pain group. Visual Analogue Scale (VAS) was applied to grade the pain, the patients in cancer pain group were treated with morphine, and the dosage of morphine within 24 h was recorded. Then, the genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood of the research subjects, and the polymorphisms rs1042173 and rs7224199 of SLC6A4 gene were detected.

RESULTS: There was a difference in the genotype distribution of SLC6A4 gene rs7224199 between painless group and cancer pain group (p=0.004), and the frequency of GG genotype was remarkably higher in cancer pain group [75 (0.375)]. The frequency of heterozygous model AC of rs1042173 and recessive model GT + TT of rs7224199 in cancer pain group was evidently lower than that in painless group (p=0.048, p=0.043). Besides, the lung cancer patients in cancer pain group had markedly lower frequency of AG haplotype (p=0.000), but notably higher frequency of AT (p=0.000) and CG (p=0.000) haplotypes of SLC6A4 gene rs1042173 and rs7224199 than those in painless group. No significant differences in genotypes of SLC6A4 gene rs1042173 (p=0.241) and rs7224199 (p=0.316) were detected among the degrees of cancer pain in cancer pain group. The analgesic dosage of morphine for the lung cancer patients was prominently correlated with the genotypes of SLC6A4 gene rs1042173 in cancer pain group. Moreover, in cancer pain group, there were significant differences in the dosage within 24 h (p=0.025), at 24 h after weight correction (p=0.001) and at 24 h after correction of weight and body surface area (p=0.000) among the genotypes, and the morphine dosage for the patients with CC genotype was significantly lower. Furthermore, the morphine dosage within 24 h (p=0.047), at 24 h after weight correction (p=0.042) and at 24 h after correction of weight and body surface area (p=0.031) were distinctly associated with the haplotypes of SLC6A4 gene in cancer pain group, of which the patients with CT haplotype were administered with a remarkably lower morphine dosage.

CONCLUSIONS: The morphine dosage for analgesia has significant correlations with SLC6A4 gene polymorphisms in patients with lung cancer.

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