Risk Factors for Malignant Melanoma In Situ
Risk Factors for Malignant Melanoma In Situ
The incidences of malignant melanoma in situ (MMIS) and invasive malignant melanoma are rising in the United States, but few studies have examined risk factors for MMIS. We evaluated the risk of MMIS according to the host phenotype and the ultraviolet index of the state of residence. Prospective data were collected via biennial questionnaires from 250,151 women and men aged ≥20 years in the Nurses' Health Study (1980–2008), the Nurses' Health Study 2 (1989–2009), and the Health Professionals Follow-up Study (1986–2008). During 7,144,820 person-years of follow-up, 888 incident MMIS lesions occurred, representing 33% of all incident malignant melanoma. Meta-analysis across the cohorts demonstrated that the presence of multiple nevi on the extremities conferred the highest relative risk for MMIS (relative risk = 3.18, 95% confidence interval: 2.59, 3.90). Family history of melanoma, number of severe sunburns, sunburn susceptibility, hair color, and Fitzpatrick skin types I, II, and III were significantly associated with an increased risk of MMIS. Conversely, the ultraviolet index of the state of residence at birth, at age 15 years, and at age 30 years was not associated with increased risk of MMIS. Continued study of MMIS and associated risk factors will help identify persons who are most at risk and elucidate the role of MMIS within the spectrum of cutaneous melanoma.
The incidence of invasive malignant melanoma is rapidly rising both in the United States and worldwide. Although malignant melanoma in situ (MMIS) trails invasive malignant melanoma in absolute numbers, the incidence of MMIS has been increasing at a greater rate than that of invasive malignant melanoma. MMIS now represents about 40% of all melanoma diagnosed in the United States, up from an estimated 22% in 1988. The reasons for this increase are multifactorial; they may include increased screening and diagnosis, as well as environmental, behavioral, and educational changes over time. Recent studies on melanoma in the United States have demonstrated that despite the increased diagnosis of thinner melanoma lesions, overall melanoma mortality has remained constant, and investigators have called for better risk identification and screening modalities.
MMIS is thought to represent the noninvasive precursor lesion to invasive and metastatic melanoma, in which malignant melanocytes grow in the epidermis during a noninvasive radial growth phase. It has been proposed that MMIS accumulates mutations, such as those in the neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS); the v-raf murine sarcoma viral oncogene homolog B1 (BRAF); the SRY (sex determining region Y)-box 2 gene (SOX2); and others in a stepwise fashion, gaining the capability to invade the underlying dermis and to metastasize.
A recent study of MMIS showed that it is smaller than its invasive counterpart, with approximately 50% of tumors measuring less than 6 mm in diameter. MMIS is more likely to be detected by a dermatologist than by the patient or a family member, and patient concern upon presentation of MMIS lesions is usually low. Although melanoma, when diagnosed in situ, does not affect host mortality, invasive malignant melanoma, even in its earliest stages, confers increased mortality. For these reasons, identification of persons at high risk and their enrollment in careful screening programs are important and have proven effective in decreasing invasive melanoma and subsequent mortality.
To further characterize risk factors for MMIS, we conducted a prospective study on 3 large cohorts of US women and men with 888 incident MMIS lesions, which, to our knowledge, is the largest study of its kind to date. Strict criteria excluded any person with a history of cancer or skin cancer to minimize diagnostic bias. To further characterize risk, we conducted analyses by Fitzpatrick skin phototype and the ultraviolet index of state of residence at birth, at age 15 years, and at age 30 years.
Abstract and Introduction
Abstract
The incidences of malignant melanoma in situ (MMIS) and invasive malignant melanoma are rising in the United States, but few studies have examined risk factors for MMIS. We evaluated the risk of MMIS according to the host phenotype and the ultraviolet index of the state of residence. Prospective data were collected via biennial questionnaires from 250,151 women and men aged ≥20 years in the Nurses' Health Study (1980–2008), the Nurses' Health Study 2 (1989–2009), and the Health Professionals Follow-up Study (1986–2008). During 7,144,820 person-years of follow-up, 888 incident MMIS lesions occurred, representing 33% of all incident malignant melanoma. Meta-analysis across the cohorts demonstrated that the presence of multiple nevi on the extremities conferred the highest relative risk for MMIS (relative risk = 3.18, 95% confidence interval: 2.59, 3.90). Family history of melanoma, number of severe sunburns, sunburn susceptibility, hair color, and Fitzpatrick skin types I, II, and III were significantly associated with an increased risk of MMIS. Conversely, the ultraviolet index of the state of residence at birth, at age 15 years, and at age 30 years was not associated with increased risk of MMIS. Continued study of MMIS and associated risk factors will help identify persons who are most at risk and elucidate the role of MMIS within the spectrum of cutaneous melanoma.
Introduction
The incidence of invasive malignant melanoma is rapidly rising both in the United States and worldwide. Although malignant melanoma in situ (MMIS) trails invasive malignant melanoma in absolute numbers, the incidence of MMIS has been increasing at a greater rate than that of invasive malignant melanoma. MMIS now represents about 40% of all melanoma diagnosed in the United States, up from an estimated 22% in 1988. The reasons for this increase are multifactorial; they may include increased screening and diagnosis, as well as environmental, behavioral, and educational changes over time. Recent studies on melanoma in the United States have demonstrated that despite the increased diagnosis of thinner melanoma lesions, overall melanoma mortality has remained constant, and investigators have called for better risk identification and screening modalities.
MMIS is thought to represent the noninvasive precursor lesion to invasive and metastatic melanoma, in which malignant melanocytes grow in the epidermis during a noninvasive radial growth phase. It has been proposed that MMIS accumulates mutations, such as those in the neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS); the v-raf murine sarcoma viral oncogene homolog B1 (BRAF); the SRY (sex determining region Y)-box 2 gene (SOX2); and others in a stepwise fashion, gaining the capability to invade the underlying dermis and to metastasize.
A recent study of MMIS showed that it is smaller than its invasive counterpart, with approximately 50% of tumors measuring less than 6 mm in diameter. MMIS is more likely to be detected by a dermatologist than by the patient or a family member, and patient concern upon presentation of MMIS lesions is usually low. Although melanoma, when diagnosed in situ, does not affect host mortality, invasive malignant melanoma, even in its earliest stages, confers increased mortality. For these reasons, identification of persons at high risk and their enrollment in careful screening programs are important and have proven effective in decreasing invasive melanoma and subsequent mortality.
To further characterize risk factors for MMIS, we conducted a prospective study on 3 large cohorts of US women and men with 888 incident MMIS lesions, which, to our knowledge, is the largest study of its kind to date. Strict criteria excluded any person with a history of cancer or skin cancer to minimize diagnostic bias. To further characterize risk, we conducted analyses by Fitzpatrick skin phototype and the ultraviolet index of state of residence at birth, at age 15 years, and at age 30 years.
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