Melanoma: Halpern A

Houghton AN, Coit DG, Daud A, Dilawari RA, Dimaio D, Gollob JA, Haas NB, Halpern A, Johnson TM, Kashani-Sabet M, Kraybill WG, Lange JR, Martini M, Ross MI, Samlowski WE, Sener SF, Tanabe KK, Thompson JA, Trisal V, Urist MM, Walker MJ, Anonymous00370. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #16884669 No free full text.

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Busam KJ, Marghoob AA, Halpern A. · No affiliation provided · J Invest Dermatol. · Pubmed #16193554 links to  free full text

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Sachs DL, Marghoob AA, Halpern A. · Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · Clin Geriatr Med. · Pubmed #11535425 No free full text.

Abstract: This article describes the clinical features, treatment options, and prognosis of the most common skin cancers: basal cell carcinoma, squamous cell carcinoma, and melanoma. Emphasis is placed on specific issues that need to be considered when dealing with cancers of the skin in the elderly population. In addition, issues surrounding the early detection and prevention of skin cancer are addressed.

Marghoob AA, Blum R, Nossa R, Busam KJ, Sachs D, Halpern A. · Dermatology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. · Arch Dermatol. · Pubmed #11453811 links to  free full text

Abstract: BACKGROUND: Patients with the atypical mole syndrome have multiple dysplastic nevi that appear to be randomly distributed on certain preferred anatomical sites such as the upper back. These dysplastic nevi are thought to be acquired melanocytic nevi that begin appearing at puberty. To our knowledge, the presence of agminated atypical (dysplastic) nevi has not been reported. OBSERVATION: We describe a patient with the atypical mole syndrome who has more than 100 melanocytic nevi, many of which are clinically atypical and one of which proved to be a melanoma. Among his many melanocytic nevi is a cluster of approximately 50 nevi that are distributed in an area measuring 5 x 3 cm. The histopathologic features of these nevi are consistent with the diagnosis of "dysplastic nevus." CONCLUSIONS: To our knowledge, agminated atypical (dysplastic) nevi have not been described previously. The presence of agminated atypical (dysplastic) nevi in a patient with the atypical mole syndrome can be theorized to arise because of loss of heterozygosity.

Cotignola J, Roy P, Patel A, Ishill N, Shah S, Houghton A, Coit D, Halpern A, Busam K, Berwick M, Orlow I. · Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · J Negat Results Biomed. · Pubmed #17958893 links to  free full text

Abstract: BACKGROUND: The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression. METHODS: We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test. RESULTS: All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729. CONCLUSION: This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.

Cotignola J, Reva B, Mitra N, Ishill N, Chuai S, Patel A, Shah S, Vanderbeek G, Coit D, Busam K, Halpern A, Houghton A, Sander C, Berwick M, Orlow I. · Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · BMC Med Genet. · Pubmed #17346338 links to  free full text

Abstract: BACKGROUND: Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. METHODS: We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. RESULTS: We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. CONCLUSION: This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

Lea CS, Holly EA, Hartge P, Lee JS, Guerry D, Elder DE, Halpern A, Sagebiel RW, Tucker MA. · Statistics and Epidemiology Program, Research Triangle Institute International, Research Triangle Park, NC, USA. · Am J Epidemiol. · Pubmed #17158470 links to  free full text

Abstract: Reproductive hormonal factors may have a potential role in cutaneous melanoma. This study estimated the risk of melanoma in women related to self-reported changes in nevi during pregnancy, while using oral contraceptives and/or hormone replacement therapy. Trained interviewers administered a questionnaire obtaining information about oral contraceptive use, hormone replacement therapy, reproductive history, sun exposure, occupation, and medical history from 318 Caucasian women newly diagnosed between 1991 and 1992 from two pigmented lesion clinics in San Francisco, California, and Philadelphia, Pennsylvania. A total of 395 frequency-matched control participants were recruited from hospital-affiliated outpatient clinics. Clinicians conducted skin examinations to assess the number and type of nevi, extent of freckling, solar damage, and skin type. For women aged less than 55 years, there was an association between a livebirth 5 years before diagnosis (odds ratio = 2.6, 95% confidence interval: 1.3, 5.3) and between number of births and melanoma risk (for > or = 3 births: odds ratio = 3.3, 95% confidence interval: 1.7, 6.5; ptrend < 0.001). Changes in nevi during recent pregnancies were a risk factor for melanoma, based upon small numbers (odds ratio = 2.9, 95% confidence interval: 1.1, 8.1). Oral contraceptive use and hormone replacement therapy were not associated with melanoma risk.

Fears TR, Guerry D, Pfeiffer RM, Sagebiel RW, Elder DE, Halpern A, Holly EA, Hartge P, Tucker MA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. · J Clin Oncol. · Pubmed #16728488 No free full text.

Abstract: PURPOSE: We developed a model to estimate the 5-year absolute risk of melanoma to efficiently identify individuals at increased risk of melanoma for potential interventions. PATIENTS AND METHODS: We used data from a case-control study with 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia, PA and San Francisco, CA; matched controls were 945 patients from outpatient clinics with similar catchment areas. All participants underwent extensive interviews and skin examinations. We selected easily obtained clinical characteristics and responses to simple questions for study in order to develop sex-specific relative risk models. These models were combined with incidence and mortality rates by United States geographic areas to develop estimates of the absolute risk of developing melanoma within 5 years. RESULTS: Relative risk models yielded an attributable risk of 86% for men and 89% for women, using at most seven variables. Attributable risks did not vary by age, ultraviolet B flux or hours outdoors. The absolute individual risks varied widely, depending on age, other host characteristics, and geographic area. Individual absolute risk can be estimated using a program available online. CONCLUSION: Our procedures allow for estimating the absolute risk of developing melanoma to assist in the identification of patients at high risk. Such high-risk individuals could undergo interventions including a complete skin examination, counseling to avoid sun exposures, regular self and professional surveillance, or participation in prevention trials. It is important to emphasize that these projections are not intended to identify current melanoma cases.

Ben-Porat L, Panageas KS, Hanlon C, Patel A, Halpern A, Houghton AN, Coit D. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · Cancer. · Pubmed #16331596 links to  free full text

Abstract: BACKGROUND: The objectives of the current study were to examine how the estimated stage-specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared with the 1997 AJCC staging system and to contrast the predictive accuracy of the 2 staging systems. METHODS: There were 5847 consecutive melanoma patients who presented to Memorial Sloan-Kettering Cancer Center from 1996 to 2004 and who were entered prospectively into a data base. These patients were staged according to both the 1997 and 2002 AJCC staging criteria. Overall survival estimates were determined using the Kaplan-Meier method. The overall predictive accuracy of the two staging systems was compared using concordance estimation. RESULTS: In total, 1035 patients were shifted to a lower stage in the 2002 staging system, whereas only 15 patients were upstaged. The number of patients with Stage I melanoma increased by 697 under the 2002 system (n = 2166 patients) compared with the 1997 system (n = 1463 patients). Because of the changes in 2002, the estimated 5-year overall survival for patients with Stage II melanoma decreased considerably, from 79% (1997) to 64% (2002). With the initiation of subgroups in 2002, it became apparent that patients with Stage III melanoma were very heterogeneous in terms of their survival probabilities (5-yr overall survival ranged from 70% in patients with Stage IIIA disease to 24% in patients with Stage IIIC disease). Furthermore, in the 2002 system, there was substantial prognostic overlap between Stage II and Stage III. Despite the increased complexity of the 2002 system, the 2 staging systems had similar concordance estimates: 58% for the 1997 staging system compared with 58% (ignoring the subgroups) and 59% (with subgroups) for the 2002 system. CONCLUSIONS: Estimates of stage-specific survival were altered substantially by the changes made in the 2002 AJCC staging system for melanoma, particularly for Stage II. Stage subgroups that were added in the 2002 system resulted in a large diversity of risk within Stage III. This must be taken into account to stratify patients properly for clinical trials. The increased complexity of the 2002 system did not improve its predictive ability over the simpler 1997 system, highlighting the importance of developing individualized risk-prediction models.

Busam KJ, Halpern A, Marghoob AA. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · Am J Surg Pathol. · Pubmed #16330954 No free full text.

Abstract: We report a case of metastatic melanoma colliding with and colonizing a basal cell carcinoma (BCC) on the head of a 69-year-old man. The man had a prior history of multiple primary BCCs and melanomas. One of his primary melanomas, on the left scalp, recurred locally and resulted in the development of numerous in-transit metastases. A bluish nodule was noted on the postauricular area with clinical features consistent with a pigmented BCC. Dermoscopy showed some large gray-blue ovoid structures and blood vessels, features also consistent with BCC. However, the histologic features revealed that the nodule consisted of both metastatic melanoma as well as BCC. Melanoma was present adjacent to as well as within the epithelium of the BCC. The intimate association of melanoma cells within the nodules of BCC simulated the pattern of so-called "malignant basomelanocytic tumor," a recently proposed novel entity. To our knowledge, this is the first description of metastatic melanoma colonizing a BCC.

Rutter JL, Bromley CM, Goldstein AM, Elder DE, Holly EA, Guerry D, Hartge P, Struewing JP, Hogg D, Halpern A, Sagebiel RW, Tucker MA. · Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-7236, USA. · Cancer. · Pubmed #15529312 links to  free full text

Abstract: BACKGROUND: Data addressing the interfamilial heterogeneity of melanoma are limited. In the current study, the authors assessed melanoma risk according to family history of melanoma and other melanoma-associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies. METHODS: The authors obtained patient histories of malignancy in first-degree relatives as part of a clinic-based case-control study. The case group included 737 newly diagnosed patients with invasive melanoma, and the control group included 1021 outpatients from clinics at the same medical centers. To assess heterogeneity of risk among families affected by melanoma, a nonparametric method was used to detect extrabinomial variation. In addition, selected patients with melanoma (n=133) were tested for germline mutations in CDKN2A. RESULTS: The adjusted odds ratio associated with a family history of melanoma was 1.7 (95% confidence interval, 1.1-2.7). Family histories of pancreatic, gastrointestinal, brain, breast, or lymphoproliferative disease did not increase the risk of melanoma significantly. Among case families, significant evidence of familial heterogeneity was found for melanomas, but not for pancreatic or gastrointestinal malignancies. Two mutations in CDKN2A previously associated with melanoma risk were identified among the 133 patients tested in the case group; mutation detection did not differ between families with low and high heterogeneity scores. CONCLUSIONS: Familial heterogeneity testing in the study population did not improve the selection of high-risk families for genetic study. Even in a large case-control study, few families that had multiple members with melanoma were identified, and family members with pancreatic malignancies were rare.

Millen AE, Tucker MA, Hartge P, Halpern A, Elder DE, Guerry D, Holly EA, Sagebiel RW, Potischman N. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7344, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #15184262 links to  free full text

Abstract: BACKGROUND: Malignant melanoma has been one of the most rapidly increasing cancers within the United States with few modifiable risk factors. This study investigates risk related to dietary factors, which are potentially modifiable. METHODS: Newly diagnosed patients with melanoma (n = 502) were recruited from pigment lesion clinics and controls (n = 565) were recruited from outpatient clinics. To investigate the relationship between melanoma and dietary factors in this case-control study, study subjects were requested to complete a food frequency questionnaire, which assessed diet over the previous year. Using logistic regression, odds ratios (ORs) for melanoma were computed for nutrient and alcohol intake. RESULTS: Persons in high versus low quintiles of energy-adjusted vitamin D, alpha-carotene, beta-carotene, cryptoxanthin, lutein, and lycopene had significantly reduced risk for melanoma (ORs < or = 0.67), which remained after adjustment for presence of dysplastic nevi, education, and skin response to repeated sun exposure. Addition of micronutrients from supplements did not add an additional reduction in risk. High alcohol consumption was associated with an increased risk for melanoma, which remained after adjustment for confounders [OR (95% confidence interval) in highest versus lowest quintiles, 1.65 (1.09-2.49)]. CONCLUSIONS: Diets consisting of foods rich in vitamin D and carotenoids and low in alcohol may be associated with a reduction in risk for melanoma. These analyses should be repeated in large, prospective studies.

Berwick M, Orlow I, Mahabir S, Myskowski P, Coit D, Brady MS, Roy P, Song Y, Canchola R, Barz A, Halpern A, Bolognia J, Eng S, Elahi A, Begg CB. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · Eur J Cancer Prev. · Pubmed #15075790 No free full text.

Abstract: Estimation of the relative risk of cancer due to rare germline mutations using population-based epidemiological techniques is challenging, since studies with very large numbers of subjects are required. In this pilot study using a novel study design, we evaluated the role of INK4A mutations in melanoma by comparing patients with multiple primary melanomas to those with single primaries. Patients were ascertained from the Surgery and Dermatology Clinics at Memorial Sloan-Kettering Cancer Center and at the Yale University Pigmented Lesion Clinic. Subjects completed a questionnaire covering risk factors for melanoma and were tested for INK4A mutations. Five (8%) of 65 patients with multiple primaries had a mutation, compared with none of 88 patients with single primaries (P=0.03). Examination of other factors, such as number of nevi on the arms of the patients, fair skin, hair and eye colour, and other phenotypic characteristics associated with the risk of melanoma, demonstrates that these factors exhibit higher prevalence in the multiple primary cases than in the single primaries. These results provide evidence of the utility of the new study design in evaluating the impact of rare but highly penetrant cancer risk factors.

Busam KJ, Sachs DL, Coit DG, Halpern A, Hwu WJ. · Department of Pathology, Clinical Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · J Cutan Pathol. · Pubmed #12859746 No free full text.

Abstract: BACKGROUND: Malignancies may be associated with paraneoplastic cutaneous manifestations, including pigmentary disorders. METHODS: The clinical findings were reviewed. Skin and tumor tissue samples were examined by routine histology, immunohistochemistry, and in one case also by electron microscopy. RESULTS: Two patients developed diffuse melanotic macules and papules associated with visceral adenocarcinoma. One patient was a 64-year-old man with advanced carcinoma of the distal esophagus. The other was a 62-year-old man with metastatic pulmonary adenocarcinoma. The detection of the primary tumor in both patients was preceded by the rapid onset of melanotic macules and papules in the anogenital region and in one patient also around both nipples. The pigmented lesions were histologically characterized by a lentiginous melanocytic proliferation of large and heavily pigmented melanocytes associated with hyperpigmentation of adjacent keratinocytes. Both patients had been misdiagnosed as having epidermotropic metastatic malignant melanoma. None of them had prior, concurrent, or subsequent cutaneous or extracutaneous invasive melanoma. Both patients died of metastatic adenocarcinoma. CONCLUSION: Eruptive melanotic macules and papules represent an under-recognized paraneoplastic syndrome. The cases illustrate a diagnostic pitfall for clinicians and pathologists unaware of this phenomenon.

Geller AC, Sober AJ, Zhang Z, Brooks DR, Miller DR, Halpern A, Gilchrest BA. · Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. · Cancer. · Pubmed #12237925 links to  free full text

Abstract: BACKGROUND: Recently, the Institute of Medicine (2000) and the Third United States Preventive Services Task Force (2001) called for studies to help clinicians identify patients, especially elderly patients, who are at high risk for melanoma. In the current study, the authors sought to identify factors associated with a high yield in skin cancer screening and to explore strategies for improving mass screenings for melanoma. METHODS: The authors analyzed the data base of the 242,374 skin cancer screenings conducted on more than 206,000 Americans who attended the American Academy of Dermatology National Skin Cancer Screening Programs during the period 1992-1994. RESULTS: Ninety-six percent of 3476 screenees with a presumptive diagnosis of melanoma or possible melanoma were contacted, and follow-up records were obtained for 73% of screenees. Of these, 363 screenees had histologically proven melanoma. Middle-aged and older men (age >or= 50 years) comprised only 25% of screenees but comprised 44% of those with a confirmed diagnosis of melanoma. The overall yield of melanoma (the number of confirmed diagnoses per the number of screenees) was 1.5 per 1000 screenings (363 diagnoses of 242,374 screenees) compared with a yield of 2.6 per 1000 screenings among men age >or= 50 years. The yield was improved further for men age >or= 50 years who reported either a changing mole (4.6 per 1000 screenings) or skin types I and II (3.8 per 1000 screenings). The predictive value of a screening diagnosis of melanoma was more than twice as high for men age >or= 50 years with either a changing mole or skin types I and II compared with all other participants. CONCLUSIONS: The yield of mass screening for melanoma would be improved by outreach to middle-aged and older men, with particular focus on men with changing moles or with skin types I and II. Primary care physicians should be attuned to the risk factors among all of their patients but should be alerted in particular to the heightened risk of melanoma for men age >or= 50 years. Formal assessment of the impact of targeted screening on mortality warrants further study.

Fears TR, Bird CC, Guerry D, Sagebiel RW, Gail MH, Elder DE, Halpern A, Holly EA, Hartge P, Tucker MA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. · Cancer Res. · Pubmed #12124332 links to  free full text

Abstract: Sunlight is the major environmental risk factor for melanoma. Descriptive studies have shown latitudinal variation in population incidence and mortality rates [D. C. Whiteman and A. C. Green, Int. J. Dermatol., 38: 481-489, 1999, and B. K. Armstrong, Australian J. Dermatol., 38 (Suppl. 1): 51-56, 1997]. In analytic studies, individual exposure has been particularly difficult to quantify. Lifetime residential history was coupled with levels of midrange UV radiation (UVB flux) to provide a measure of individual exposure to sunlight thought to be less subject to misclassification and recall bias. Data were analyzed from 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia and San Francisco. Matched controls were 945 patients from outpatient clinics with similar catchment areas. The association of melanoma risk and history of UVB flux along with the usual outdoor exposure risk factors were studied. A 10% increase in the average annual UVB flux was associated with a 19% [95% confidence interval (CI), 5-35%] increase in individual odds for melanoma for men and 16% (95% CI, 2-32%) for women. In men, a 10% increase in hours outdoors was associated with a 2.8% (95% CI, 1.2-4.5%) increase in odds. Even in women who could develop a deep tan, a 10% increase in hours outdoors was associated with a 5.8% increase in odds (95% CI, 1.4-10.4%). The association between melanoma risk and average annual UVB flux was strong and consistent for men and for women. The association with total adult hours outdoors was notable for men of all skin types and women who develop a suntan.

Goldstein AM, Chidambaram A, Halpern A, Holly EA, Guerry IV D, Sagebiel R, Elder DE, Tucker MA. · Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. · Melanoma Res. · Pubmed #11828258 No free full text.

Abstract: To date, two genes have been implicated in melanoma pathogenesis. The first, CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of melanoma-prone families. The second, CDK4, is an oncogene with co-segregating germline mutations detected in only three kindreds worldwide. We examined 16 American melanoma-prone families for mutations in all coding exons of CDK4 and screened additional members of two previously reported families with the Arg24Cys germline CDK4 mutation to evaluate the penetrance of the mutation. No new CDK4 mutations were identified. In the two Arg24Cys families, the penetrance was estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out of one in situ melanoma patient, five out of 13 dysplastic naevi patients, two out of 15 unaffected family members, and none out of 10 spouses carried the Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the Arg24Cys mutation. Thus the phenotype observed in melanoma-prone CDK4 families appears to be more complex than just the CDK4 mutation. Both genetic and environmental factors are likely to contribute to the occurrence of melanoma and dysplastic naevi in these families. In summary, although CDK4 is a melanoma susceptibility gene, it plays a minor role in hereditary melanoma.

Kanetsky PA, Holmes R, Walker A, Najarian D, Swoyer J, Guerry D, Halpern A, Rebbeck TR. · Departments of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #11352862 links to  free full text

Abstract: The mu and theta classes of glutathione S-transferases (GST) may affect the development of cutaneous malignant melanoma (CMM) by decreasing cellular oxidative stress in skin. These isozymes are absent in a large proportion of the population because of germ-line homozygous deletions in the genes encoding GSTM1 and GSTT1. To determine the association between GSTM1 and GSTT1 homozygous deletions (GSTM1 null and GSTT1 null, respectively) and CMM, we studied 212 patients with CMM, 150 patients with CMM and dysplastic nevi (DN), 147 patients with DN alone, and 124 healthy persons without CMM or DN. Comparing CMM cases (n = 362) to participants without CMM (n = 271), we found no association with GSTM1 null [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.86-1.6] or GSTT1 null (OR, 0.82; 95% CI, 0.56-1.2), either independently or in combination (OR, 1.4; 95% CI, 0.81-2.2), after adjusting for age. However, among the subset of participants with red or blond hair, those with CMM were twice as likely to carry GSTM1 null (OR, 2.2; 95% CI, 1.2-4.2) and nearly 10-fold more likely to carry both GSTM1 null and GSTT1 null (OR, 9.5; 95% CI, 1.2-73) compared with those without CMM. These data suggest that among persons with hair colors traditionally associated with increased risk for melanoma, absence of both GSTM1 and GSTT1 may act to further elevate CMM risk.

Hay J, Shuk E, Brady MS, Berwick M, Ostroff J, Halpern A. · No affiliation provided · Arch Dermatol. · Pubmed #18427057 No free full text.

This publication has no abstract.