GSTM1 copy number and promoter haplotype as predictors for risk of recurrence and/or second primary tumor in patients with head and neck cancer

Zhang, Xuemei; Huang, Maosheng; Wu, Xifeng; Kadlubar, Susan; Lin, Jie; Yu, Xinfeng; Fan, Chun‐Yang; Kadlubar, Fred F.

doi:10.2147/pgpm.s35949

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…Approximately 27% of Black individuals and 50% of White and Asian individuals are homozygous carriers of the GSTM1 deletion or null allele (GSTM1[0]) (13). Those with the deletion variant lack GSTM1 enzyme function (14)(15)(16)(17)(18)(19). Chimpanzees are the only other primate species that have the common GSTM1 deletion, reaching 0.41 (41%) in allele frequency among these primates (20).…”

Section: Introductionmentioning

confidence: 99%

Role of GSTM1 in Hypertension, CKD, and Related Diseases across the Life Span

Levy

2022

Kidney360

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Over twenty years after the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, chronic kidney disease (CKD) remains a major public health burden with very limited therapeutic options to halt or slow kidney disease progression at all ages. The general consensus is that oxidative stress contributes to CKD development and progression. Yet, to date, there is no clear evidence that broad use of antioxidant therapy provides a beneficial effect in CKD. Understanding the specific pathophysiologic mechanisms in those who are genetically most susceptible to oxidative stress is a crucial step to inform therapy in an individualized medicine approach, taking into account differing exposures and risks across the lifespan. GSTM1 (glutathione-S-transferase mu 1) is a phase II enzyme involved in inactivation of reactive oxygen species and metabolism of xenobiotics. In particular, those with the highly prevalent GSTM1 null genotype (GSTM1(0/0)) may be more susceptible to kidney disease progression due to impaired capacity to handle the increased oxidative stress burden in disease states and might specifically benefit from therapy that targets the redox imbalance mediated by loss of GSTM1 enzyme. In this review, we will discuss the studies implicating the role of GSTM1 deficiency in kidney and related diseases from experimental rodent models to humans, from the prenatal period through senescence, and the potential underlying mechanism.

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Section: Introductionmentioning

confidence: 99%

Role of GSTM1 in Hypertension, CKD, and Related Diseases across the Life Span

Levy

2022

Kidney360

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“…Head and neck cancer is one of the most common cancers worldwide. In 2012, about 52,000 new cases were diagnosed in the United States and of these, about 11,500 patients will die from the disease [1] . The current standard of care for head and neck cancer includes surgical resection of the tumor followed by radiation and chemotherapy [2] .…”

Section: Introductionmentioning

confidence: 99%

The Rapalogue, CCI-779, Improves Salivary Gland Function following Radiation

et al. 2014

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The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.

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