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

Shaowei Wu, Helen Kuo, Wen Qing Li, Alvaro Laga Canales, Jiali Han, Abrar A. Qureshi

Research output: Contribution to journalArticle

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, ptrend = 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.

Original languageEnglish (US)
Pages (from-to)1379-1386
Number of pages8
JournalCancer Causes and Control
Volume25
Issue number10
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Melanoma
Skin
Mutation
Survival
Nurses
Health
Solar System
Paraffin
Formaldehyde
Cohort Studies
Logistic Models
Odds Ratio
Regression Analysis

Keywords

  • BRAF
  • Melanoma
  • NRAS
  • Sun exposure
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Association between BRAF V600E and NRAS Q61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma. / Wu, Shaowei; Kuo, Helen; Li, Wen Qing; Canales, Alvaro Laga; Han, Jiali; Qureshi, Abrar A.

In: Cancer Causes and Control, Vol. 25, No. 10, 01.01.2014, p. 1379-1386.

Research output: Contribution to journalArticle

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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, ptrend = 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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AU - Kuo, Helen

AU - Li, Wen Qing

AU - Canales, Alvaro Laga

AU - Han, Jiali

AU - Qureshi, Abrar A.

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N2 - 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, ptrend = 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.

AB - 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, ptrend = 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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