COMT Val158Met Affects the Analgesic Response to Acupuncture Among Cancer Survivors With Chronic Pain.

Catechol-O-methyltransferase (COMT) is the major enzyme involved in the catabolism of dopamine, a neurotransmitter in the brain's reward system. The common COMT polymorphism Val158Met (rs4680 G>A) modulates pain response to opioids through a reward-motivated mechanism; however, its role in nonpharmacological pain medicine has not been clinically characterized. We genotyped 325 participants from a randomized controlled trial of cancer survivors with chronic musculoskeletal pain. We found that carrying methionine at position 158 (158Met) of COMT, encoded by the A allele, significantly increased the analgesic response to electroacupuncture (74% vs 50%; odds ratio [OR]: 2.79; 95% confidence interval [CI]: 1.31, 6.05; P < .01), but not to auricular acupuncture (68% vs 60%; OR: 1.43; 95% CI: .65, 3.12; P = .37) or usual care (24% vs 18%; OR: 1.46; 95% CI: .38, 7.24; P = .61) compared to Val/Val. These findings raise the possibility that COMT Val158Met might be an important predictor of analgesic response to electroacupuncture, providing novel insights into precision nonpharmacologic pain management tailored to individual genetic backgrounds. PERSPECTIVE: This work suggests the modulating effects of the polymorphism in COMT Val158Met on the response to acupuncture. Further research needs to validate these findings, increase the mechanistic understanding of acupuncture, and guide further development of acupuncture as a precision pain management strategy.

The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study.

BACKGROUND: There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. METHODS: Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. RESULTS: Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression (two-sided Student's t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student's t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. CONCLUSIONS: Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.