Catechol-O-methyltransferase genotype (Val158met) modulates cancer-related fatigue and pain sensitivity in breast cancer survivors

Abstract

Cancer-related fatigue and pain after surgery are the most frequent and most incapacitating cancer-related symptoms after breast cancer treatment. Genetic influence of cancer-related fatigue and pain has not been previously investigated. Our aim was to examine the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on cancer-related fatigue, post-mastectomy pain, and pressure pain hypersensitivity in breast cancer survivors. One-hundred and twenty-eight (n = 128) breast cancer survivors who were treated with radiotherapy and chemotherapy participated in this study. After amplifying Val158Met polymorphisms by polymerase chain reaction, COMT genotype was divided into Val/Val, valine/methionine (Val/Met), or Met/Met. The Piper fatigue scale (PFS) was used to assess cancer-related fatigue. Neck and shoulder/axillary pain intensity was assessed with a numerical pain rate scale (0-10). Finally, pressure pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal joints, deltoid muscles, second metacarpal, and tibialis anterior muscles. Breast cancer survivors carrying the Met/Met genotype reported higher levels of fatigue (all subscales, P < 0.001), higher neck pain intensity, and lower PPT over C5-C6 joints and deltoid muscles (all, P < 0.001) relative to those with Val/Met or Val/Val genotypes. The results suggest that breast cancer survivors carrying the Met/Met genotype exhibit higher fatigue, neck pain, and pressure pain hypersensitivity over the neck and shoulder area. This study is important because it strives to understand the factors that predispose some breast cancer survivors to more cancer-related fatigue and increased pain sensitivity.

The genetic variants underlying breast cancer treatment-induced chronic and late toxicities: A systematic review

“…1 The included studies examined the genetic associations underlying one of the four treatment-induced toxicities, cardiotoxicity (N = 5), cognitive dysfunction (N = 2), fatigue (N = 4) and peripheral neuropathy (N = 8) [11,12,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. Table 1 summarizes the genetic variants that were positively associated with each toxicity.…”

“…Fatigue (Table 5) Four of the studies examined the genetic associations underlying fatigue [33][34][35][36]. The COMT gene and the genes expressing proinflammatory cytokines were investigated (IL1B-511, IL6-174, TNF-308, IL6R and C-reactive protein).…”

Genetic polymorphisms associated with common symptoms experienced by breast cancer patients

“…An earlier study [63] has revealed an association between catechol-O-methyltransferase (COMT) gene and the risk for having fatigue in breast cancer patients following breast surgery. Patients with homozygous (Met/Met) or heterozygous (Val/Met) for COMT allele variant (rs4680) had higher fatigue scores when compared with those carrying the wild type (Val/ Val).…”

“…While polymorphisms in COMT and SLC6A4 have been previously linked with fatigue [63,64], other SNPs and/or haplotypes in ADRB2, BDNF, CYP3A4, GALR1, GCH1, NPY1R HapA04, SLC6A1, SLC6A2, SLC6A3, NOS1 and TAC1 are being linked to fatigue or energy or both for the first time in breast cancer patients [53]. Of note is the presence of the three genes (NOS1, SLC6A2 and SLC6A4) that were associated with both fatigue and energy, thus further strengthening the hypothesis that fatigue and energy level though commonly grouped together are distinct symptoms.…”

“…At the time of this review, only a single study [63] reported on the influence of neurotransmitter gene polymorphisms on pain in breast cancer patients where patients harbouring the Met/Met or Val/Met genotypes for COMT (rs4680) were more likely to experience greater sensitivity to pain as compared to those carrying the Val/Val genotype. Additional studies are suggested to explore the roles of as many SNPs as possible in the COMT gene as predictors of higher sensitivity to pain in breast cancer patients and other cancer types.…”