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Association between BRAF V600E and NRAS Q61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma

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Abstract

Purpose

Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAFV600E and NRASQ61R mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses’ Health Study (NHS).

Methods

Somatic BRAFV600E and NRASQ61R mutations of 127 primary invasive melanomas from the NHS cohort were determined by pyrosequencing using formalin-fixed, paraffin-embedded block tissues. Logistic regression analyses were performed to detect the associations of mutations with melanoma risk factors, and Kaplan–Meier method was used to examine associations between mutations and survival.

Results

The odds ratios for harboring BRAFV600E mutations were 5.54 (95 % CI 1.19–25.8, p trend = 0.02) for women residing in states with UV index ≥ 7 versus those residing in states with UV index ≤5 at 30 years of age. Patients with BRAFV600E mutations tended to have shorter melanoma-specific survival when compared to patients with wild type at both loci (median survival time 110 vs. 159 months) (p = 0.03). No association was found between NRASQ61R mutation and melanoma risk factors or melanoma-specific survival.

Conclusions

BRAFV600E mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life. BRAFV600E mutation may be associated with an unfavorable prognosis among melanoma patients.

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Acknowledgments

We are deeply indebted to the staff of the Nurses’ Health Study for their valuable contributions as well as the following state cancer registries for their help: A.L., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I.L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., W.Y. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. This work was supported by the Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and two grants from NCI (P01 CA87969 and R01 CA137365).

Conflict of interest

A.Q. serves as a consultant for Abbott, Centocor, Novartis and the Centres for Disease Control and Prevention. The other authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Shaowei Wu & Helen Kuo

  2. Department of Dermatology, Warren Alpert Medical School, Brown University, 339 Eddy Street, Providence, RI, 02903, USA

    Shaowei Wu, Wen-Qing Li & Abrar A. Qureshi

  3. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Alvaro Laga Canales

  4. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA

    Jiali Han

  5. Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA

    Jiali Han

  6. Department of Dermatology, School of Medicine, Indiana University, Indianapolis, IN, USA

    Jiali Han

  7. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jiali Han & Abrar A. Qureshi

Authors
  1. Shaowei Wu
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  2. Helen Kuo
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  3. Wen-Qing Li
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Correspondence to Abrar A. Qureshi.

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Shaowei Wu and Helen Kuo share joint first authorship.

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Wu, S., Kuo, H., Li, WQ. et al. Association between BRAF V600E and NRAS Q61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma. Cancer Causes Control 25, 1379–1386 (2014). https://doi.org/10.1007/s10552-014-0443-x

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  • DOI: https://doi.org/10.1007/s10552-014-0443-x

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