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Grant Details

Grant Number: 5R03CA132175-02 Interpret this number
Primary Investigator: Han, Jiali
Organization: Brigham And Women'S Hospital
Project Title: Genetic Variants in Immunological Mediator Genes and Skin Cancer Risk
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): Genetic variants in immunological mediator genes and skin cancer risk Substantial biologic evidence indicates that the immune surveillance plays a critical role in protecting against skin cancer. However, the importance of common inherited variants in the immune surveillance genes and their interactions with constitutional host factors and UV exposure history in causing skin cancer is largely unknown; sparse data exist. We propose to examine in detail the genetic variants in 9 immunological mediator genes with the risk of melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) simultaneously in a nested case-control study within the Nurses Health Study (219 melanoma cases, 286 SCC cases, 300 BCC cases, and 874 matched controls). This innovative work will move this field forward, by evaluating common variants using complementary approaches, i.e. to evaluate putative functional SNPs and to choose tag- SNPs to test for associations of unknown common functional variants with skin cancer risk, along with exploratory pathway analyses. In addition, we will also assess the interactions between genetic variants in these genes and constitutional host factors and UV exposure history on skin cancer risk. This proposal will take advantage of the research opportunities nested within the existing well-characterized cohort, including cohort characteristics, quality of design, high follow-up rate, large sample size, rigor in prospective host risk factor assessment, and high response rate of retrospective questionnaires. Our study will also take advantage of the previously confirmed cases of the three types of skin cancers, stored blood and DNA samples, as well as previously collected information on host risk factors and UV exposure history. This research will contribute to the scientific basis for identifying high-risk individuals for skin cancer and providing individualized risk management strategies. We propose a detailed evaluation of genetic variation in immunological mediator genes in relation to the risks of melanoma, squamous cell carcinoma, and basal cell carcinoma simultaneously. This innovative work will move this field forward, by systematically evaluating common variants using complementary approaches. This research will contribute to the scientific basis for identifying individuals at high-risk for skin cancer and providing individualized risk management strategies.

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Publications

Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.
Authors: Du M, Prescott J, Cornelis MC, Hankinson SE, Giovannucci E, Kraft P, De Vivo I
Source: PLoS One, 2013;8(2), p. e52240.
EPub date: 2013 Feb 12.
PMID: 23424613
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Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study.
Authors: Prescott J, Du M, Wong JY, Han J, De Vivo I
Source: Hum Reprod, 2012 Dec;27(12), p. 3622-31.
EPub date: 2012 Aug 30.
PMID: 22940768
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A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus.
Authors: Han J, Qureshi AA, Nan H, Zhang J, Song Y, Guo Q, Hunter DJ
Source: Cancer Res, 2011 Mar 1;71(5), p. 1533-9.
EPub date: 2011 Jan 26.
PMID: 21270109
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Polymorphisms in genes involved in oxidative stress and their interactions with lifestyle factors on skin cancer risk.
Authors: He C, Qureshi AA, Han J
Source: J Dermatol Sci, 2010 Oct;60(1), p. 54-6.
EPub date: 2010 Jul 15.
PMID: 20727719
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Polymorphisms of FAS and FAS ligand genes and risk of skin cancer.
Authors: Qureshi A, Nan H, Dyer M, Han J
Source: J Dermatol Sci, 2010 Apr;58(1), p. 78-80.
EPub date: 2010 Jan 25.
PMID: 20219325
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Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study.
Authors: Nan H, Qureshi AA, Hunter DJ, Han J
Source: BMC Cancer, 2009 Jun 6;9, p. 172.
EPub date: 2009 Jun 6.
PMID: 19500394
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Polymorphisms in genes involved in DNA repair, cell growth, oxidative stress and inflammatory response, and melanoma risk.
Authors: Gu F, Qureshi AA, Kraft P, Guo Q, Hunter DJ, Han J
Source: Br J Dermatol, 2009 Jul;161(1), p. 209-12.
EPub date: 2009 May 12.
PMID: 19438866
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Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.
Authors: Nan H, Kraft P, Hunter DJ, Han J
Source: Int J Cancer, 2009 Aug 15;125(4), p. 909-17.
PMID: 19384953
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Missense polymorphisms in matrix metalloproteinase genes and skin cancer risk.
Authors: Nan H, Niu T, Hunter DJ, Han J
Source: Cancer Epidemiol Biomarkers Prev, 2008 Dec;17(12), p. 3551-7.
PMID: 19064570
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Interleukin and interleukin receptor gene polymorphisms and susceptibility to melanoma.
Authors: Gu F, Qureshi AA, Niu T, Kraft P, Guo Q, Hunter DJ, Han J
Source: Melanoma Res, 2008 Oct;18(5), p. 330-5.
PMID: 18781131
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A prospective study of telomere length and the risk of skin cancer.
Authors: Han J, Qureshi AA, Prescott J, Guo Q, Ye L, Hunter DJ, De Vivo I
Source: J Invest Dermatol, 2009 Feb;129(2), p. 415-21.
EPub date: 2008 Jul 31.
PMID: 18668136
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A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.
Authors: Han J, Kraft P, Nan H, Guo Q, Chen C, Qureshi A, Hankinson SE, Hu FB, Duffy DL, Zhao ZZ, Martin NG, Montgomery GW, Hayward NK, Thomas G, Hoover RN, Chanock S, Hunter DJ
Source: PLoS Genet, 2008 May 16;4(5), p. e1000074.
EPub date: 2008 May 16.
PMID: 18483556
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