Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss

Xu, Hong‐Xi; Robinson, Giles; Huang, Jie; Lim, Joshua Yew Suang; Zhang, Hui; Bass, Johnnie K.; Broniscer, Alberto; Chintagumpala, Murali; Bartels, Ute; Gururangan, S.; Hassall, Tim; Fisher, Michael J.; Cohn, Richard J.; Yamashita, Tetsuji; Teitz, Tal; Zuo, Jian; Onar‐Thomas, Arzu; Gajjar, Amar; Stewart, Clinton F.; Yang, Jun

doi:10.1038/ng.3217

Cited by 111 publications

(125 citation statements)

References 37 publications

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“…Ototoxicity has been significantly studied, mainly as this is a side effect mostly associated with platin therapy and due to the number of patients that experience this toxicity: 70% of children require a hearing aid after prolonged treatment with a platin drug (Xu et al 2015).…”

Section: Predicting Toxic Side Effectsmentioning

confidence: 99%

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The state-of-play and future of platinum drugs

Apps

Choi

Wheate

2015

Endocrine-Related Cancer

229

142

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The year 2015 marks the 50th anniversary since the discovery of the anticancer potential of cisplatin and it remains just as useful now as it did back then, especially for the treatment of some endocrine-related cancers like ovarian and testicular carcinomas. Since its discovery, five other platin drugs have received approval in various countries. While several new platin drugs are in preclinical development, in the last decade only two new platin drugs have entered clinical trials, LA-12 and dicycloplatin, reflecting a shift in research focus from new drug design to improved formulations of already approved platin drugs. These formulations include their encapsulation with macrocycles to slow and prevent their degradation by proteins and peptides; their attachment to nanoparticles to passively target solid tumours through the enhanced permeability and retention effect and their coordination to important nutrients, proteins, antibodies and aptamers for active tumour targeting. These formulation methods have all shown potential but none have yet yielded a new marketable medicine containing a platin drug. The reasons for this are problems of consistent drug loading, controlling the location and timing of drug release and the inherent toxicity of some of the drug delivery vehicles. In addition to drug delivery, functional genomics is now playing an increasing role in predicting patients' responses to platin chemotherapy and their likelihood of experiencing severe side effects.

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Section: Predicting Toxic Side Effectsmentioning

confidence: 99%

“…One study has identified the variant rs1872328 of the ACYP2 gene as one such marker, which codes for an enzyme that has an effect on Ca 2C homeostasis in muscles and the cochlea (Xu et al 2015). Patients that were positive for the variant were found to be predisposed to severe ototoxicity from cisplatin.…”

Section: Predicting Toxic Side Effectsmentioning

confidence: 99%

The state-of-play and future of platinum drugs

Apps

Choi

Wheate

2015

Endocrine-Related Cancer

229

142

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“…In addition, in a recent genomewide association study in 238 children with brain tumors, an inherited genetic variation in ACYP2 (rs1872328) was identified to be associated with cisplatin-related ototoxicity (HR 5 4.5; P 5 3.9 Â 10 À8 ). 64 …”

Section: Risksmentioning

confidence: 99%

Long-term Morbidity of Testicular Cancer Treatment

Fung

Fosså

Williams

et al. 2015

Urologic Clinics of North America

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“…4,5 Late effects including cardiotoxicity, ototoxicity, subsequent neoplasms, and visual disturbances have now, however, been associated with specific genetic mutations. 2,6,7 Identifying those at risk and providing appropriate and tailored follow-up care could therefore be of clinical benefit. 8 In future, personalized genetic information may thus be combined with clinical data (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…2,[6][7][8] Specifically, testing for risk of late effects may mean clinicians are better equipped to plan survivorship care, 6,7 while providing survivors with a greater level of awareness about their risks, which may assist with prevention of late effects. 2 However, there are numerous forms of testing with varied implications for different populations.…”

Section: Introductionmentioning

confidence: 99%

Genetic testing for the risk of developing late effects among survivors of childhood cancer: Consumer understanding, acceptance, and willingness to pay

Georgiou

Wakefield

McGill

et al. 2016

Cancer

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BACKGROUND Genetic testing to determine cancer survivors' risk of developing late effects from their cancer treatment will be increasingly used in survivorship care. This 2‐stage study with 64 survivors of childhood cancer and their parents investigated the preferences and acceptability of testing among those who may be at risk of developing late effects. METHODS The first stage (Stage 1) identified the most commonly perceived benefits and concerns regarding genetic testing for the risk of late effects among 24 participants. In Stage 2, during interviews, 20 survivors (55% of whom were female; mean age, 26.0 years [range, 18‐39 years]; standard deviation [SD], 0.80) and 20 parents (55% of whom were male; mean age of child survivor, 14.2 years [range, 10‐19 years]; SD, 0.79) rated the 7 most common benefits and concerns from those identified in Stage 1. Interviews were transcribed verbatim and analyzed. Decisional balance ratios were calculated by dividing the participants' average concerns scores with the average benefits scores. RESULTS Genetic testing for late effects was highly acceptable: 95% of participants leaned toward testing, and the majority (65.9%) would pay up to Australian $5000. The majority (97.2%) reported it was acceptable to wait for up to 6 months to receive results, and to be offered testing immediately after treatment or when the survivor reached adulthood (62.9%). Survivors and parents had a highly positive decisional balance (Mean (M), 0.5 [SD, 0.38] and M, 0.5 [SD, 0.39], respectively), indicating that perceived benefits outweighed concerns. CONCLUSIONS Although to our knowledge clinical efficacy has yet to be clearly demonstrated, survivors and parents described positive interest in genetic testing for the risk of developing late effects. Perceived benefits outweighed harms, and the majority of participants would be willing to pay, and wait, for testing. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2876–2885. © 2016 American Cancer Society

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Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss

Cited by 111 publications

References 37 publications

The state-of-play and future of platinum drugs

The state-of-play and future of platinum drugs

Long-term Morbidity of Testicular Cancer Treatment

Genetic testing for the risk of developing late effects among survivors of childhood cancer: Consumer understanding, acceptance, and willingness to pay

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