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  • American Association for Cancer Research (AACR)  (7)
  • Gallagher, Richard P.  (7)
  • Zanetti, Roberto  (7)
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  • American Association for Cancer Research (AACR)  (7)
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  • 1
    Online Resource
    Online Resource
    Sun Exposure and Melanoma Survival: A GEM Study
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 23, No. 10 ( 2014-10-01), p. 2145-2152
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 10 ( 2014-10-01), p. 2145-2152
    Abstract: Background: We previously reported a significant association between higher UV radiation exposure before diagnosis and greater survival with melanoma in a population-based study in Connecticut. We sought to evaluate the hypothesis that sun exposure before diagnosis was associated with greater survival in a larger, international population-based study with more detailed exposure information. Methods: We conducted a multicenter, international population-based study in four countries—Australia, Italy, Canada, and the United States—with 3,578 cases of melanoma with an average of 7.4 years of follow-up. Measures of sun exposure included sunburn, intermittent exposure, hours of holiday sun exposure, hours of water-related outdoor activities, ambient ultraviolet B (280–320 nm) dose, histologic solar elastosis, and season of diagnosis. Results: Results were not strongly supportive of the earlier hypothesis. Having had any sunburn in 1 year within 10 years of diagnosis was inversely associated with survival; solar elastosis—a measure of lifetime cumulative exposure—was not. In addition, none of the intermittent exposure measures—water-related activities and sunny holidays—were associated with melanoma-specific survival. Estimated ambient UVB dose was not associated with survival. Conclusion: Although there was an apparent protective effect of sunburns within 10 years of diagnosis, there was only weak evidence in this large, international, population-based study of melanoma that sun exposure before diagnosis is associated with greater melanoma-specific survival. Impact: This study adds to the evidence that sun exposure before melanoma diagnosis has little effect on survival with melanoma. Cancer Epidemiol Biomarkers Prev; 23(10); 2145–52. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-14-0431
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 2
    Online Resource
    Online Resource
    Inherited Genetic Variants Associated with Occurrence of Multiple Primary Melanoma
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 24, No. 6 ( 2015-06-01), p. 992-997
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 24, No. 6 ( 2015-06-01), p. 992-997
    Abstract: Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case–control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. Cancer Epidemiol Biomarkers Prev; 24(6); 992–7. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-14-1426
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 3
    Online Resource
    Online Resource
    Population-Based Study of Natural Variation in the Melanocortin-1 Receptor Gene and Melanoma
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 18 ( 2006-09-15), p. 9330-9337
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 18 ( 2006-09-15), p. 9330-9337
    Abstract: Natural variation in the coding region of the melanocortin-1 receptor (MC1R) gene is associated with constitutive pigmentation phenotypes and development of melanoma and nonmelanoma skin cancers. We investigated the effect of MC1R variants on melanoma using a large, international population-based study design with complete determination of all MC1R coding region variants. Direct sequencing was completed for 2,202 subjects with a single primary melanoma (controls) and 1,099 subjects with second or higher-order primary melanomas (cases) from Australia, the United States, Canada, and Italy. We observed 85 different MC1R variants, 10 of which occurred at a frequency & gt;1%. Compared with controls, cases were more likely to carry two previously identified red hair (“R”) variants [D84E, R151C, R160W, and D294H; odds ratio (OR), 1.6; 95% confidence interval (95% CI), 1.1-2.2]. This effect was similar among individuals carrying one R variant and one r variant (defined as any non-R MC1R variant; OR, 1.6; 95% CI, 1.3-2.2) and among those carrying only one R variant (OR, 1.5; 95% CI, 1.1-1.9). There was no statistically significant association among those carrying only one or two r variants. Effects were similar across geographic regions and categories of pigmentation characteristics or number of moles. Our results confirm that MC1R is a low-penetrance susceptibility locus for melanoma, show that pigmentation characteristics may not modify the relationship of MC1R variants and melanoma risk, and suggest that associations may be smaller than previously reported in part due to the study design. (Cancer Res 2006; 66(18): 9330-7)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-06-1634
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Disease-Associated Risk Variants in ANRIL Are Associated with Tumor-Infiltrating Lymphocyte Presence in Primary Melanomas in the Population-Based GEM Study
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 30, No. 12 ( 2021-12-01), p. 2309-2316
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 12 ( 2021-12-01), p. 2309-2316
    Abstract: Genome-wide association studies have reported that genetic variation at ANRIL (CDKN2B-AS1) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. ANRIL is located at the CDKN2A/B locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics. Methods: The Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near ANRIL, we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor NRAS/BRAF mutational status. Results: Rs518394, rs10965215, and rs564398 passed false discovery and were each associated (P ≤ 0.005) with TILs, although only rs564398 was independently associated (P = 0.0005) with TILs. Stratified by NRAS/BRAF mutational status, rs564398*A was significantly positively associated with TILs among NRAS/BRAF mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration. Conclusions: ANRIL rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to NRAS/BRAF-mutant cases. Impact: Pathways related to ANRIL variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-21-0686
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 5
    Online Resource
    Online Resource
    The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 15, No. 8 ( 2006-08-01), p. 1520-1525
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 15, No. 8 ( 2006-08-01), p. 1520-1525
    Abstract: Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which “cases” have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and “controls” have incident first primary melanoma [single primary melanoma (SPM)] . Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(8)1520–5)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-06-0270
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 6
    Online Resource
    Online Resource
    Associations of Cumulative Sun Exposure and Phenotypic Characteristics with Histologic Solar Elastosis
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 11 ( 2010-11-01), p. 2932-2941
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 11 ( 2010-11-01), p. 2932-2941
    Abstract: Background: Solar elastosis adjacent to melanomas in histologic sections is regarded as an indicator of sun exposure, although the associations of UV exposure and phenotype with solar elastosis are yet to be fully explored. Methods: The study included 2,589 incident primary melanoma patients with assessment of histologic solar elastosis in the population-based Genes, Environment, and Melanoma study. Ambient erythemal UV (UVE) at places of residence and sun exposure hours, including body site–specific exposure, were collected. We examined the association of cumulative site-specific and non–site-specific sun exposure hours and ambient UVE with solar elastosis in multivariable models adjusted for age, sex, center, pigmentary characteristics, nevi, and, where relevant, body site. Results: Solar elastosis was associated most strongly with site-specific UVE [odds ratio (OR) for top exposure quartile, 5.20; 95% confidence interval (95% CI), 3.40-7.96; P for trend & lt;0.001] and also with site-specific sun exposure (OR for top quartile, 5.12; 95% CI, 3.35-7.83; P for trend & lt;0.001). Older age (OR at & gt;70 years, 7.69; 95% CI, 5.14-11.52; P for trend & lt; 0.001) and having more than 10 back nevi (OR, 0.77; 95% CI, 0.61-0.97; P = 0.03) were independently associated with solar elastosis. Conclusion: Solar elastosis had a strong association with higher site-specific UVE dose, older age, and fewer nevi. Impact: Solar elastosis could be a useful biomarker of lifetime site-specific UV. Future research is needed to explore whether age represents more than simple accumulation of sun exposure and to determine why people with more nevi may be less prone to solar elastosis. Cancer Epidemiol Biomarkers Prev; 19(11); 2932–41. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-10-0686
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 1153420-5
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  • 7
    Online Resource
    Online Resource
    Abstract 1016: Variants in autophagy related genes and clinical characteristics in melanoma: a population-based study
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1016-1016
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1016-1016
    Abstract: Autophagy has been linked with melanoma, but no polymorphisms in autophagy related (ATG) genes have been investigated for association with melanoma prognostic indicators and survival. We examined 5 ATG gene single nucleotide polymorphisms (SNPs) in a large international multicenter population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped for five SNPs with a known or suspected impact on autophagic flux. While we did not identify an association with survival, a significant association was identified between the minor allele for an ATG16L polymorphism (rs2241880) and a decrease in Breslow thickness (p = 0.03), earlier tumor stage at diagnosis (OR 0.47, 95% CI 0.27-0.81, p = 0.02) and younger age at diagnosis (p = 0.02). In addition, two SNPs in ATG5 (rs2245214 and rs510432) were found to be significantly associated with increased tumor stage of melanoma (OR 1.84 95% CI 1.12-3.02, p = 0.05; OR 1.47 95% CI 1.11-1.94, p = 0.03). Finally, we identified inverse associations between the minor allele of rs2245214 and melanomas on the scalp or neck (OR 0.20, 95% CI 0.05-0.86, p = 0.03); rs1864182 (OR 0.42, 95% CI 0.21-0.88, p = 0.02) and brisk TILs, and rs510432 (OR 0.55 95% CI 0.34-0.87, p = 0.01) with non-brisk TILs, although they were not globally significant. In summary, our data suggests that ATG SNPs, while not associated with survival, may be associated with Breslow thickness, tumor stage, age at diagnosis, and aggressive histopathological factors. These associations could contribute to our current understanding of the significant role of autophagy in melanoma progression. Citation Format: Kirsten A. m. White, Li Luo, Todd A. Thompson, Salina Torres, Chien-An A. Hu, Nancy E. Thomas, Hoda Anton-Culver, Stephen B. Gruber, Lynn From, Klaus J. Busam, Irene Orlow, Peter A. Kanetsky, Lorraine D. Marrett, Richard P. Gallagher, Roberto Zanetti, Stefano Rosso, Terry Dwyer, Anne E. Cust, Allison Venn, Colin B. Begg, Marianne Berwick, Jenna Lillyquist. Variants in autophagy related genes and clinical characteristics in melanoma: a population-based study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1016.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-1016
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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