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 |
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.
Publications
Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies.
Authors: Mons U.
, Müezzinler A.
, Schöttker B.
, Dieffenbach A.K.
, Butterbach K.
, Schick M.
, Peasey A.
, De Vivo I.
, Trichopoulou A.
, Boffetta P.
, et al.
.
Source: American journal of epidemiology, 2017-06-15; 185(12), p. 1317-1326.
PMID: 28459963
Related Citations
Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.
Authors: Liu J.J.
, Crous-Bou M.
, Giovannucci E.
, De Vivo I.
.
Source: The Journal of nutrition, 2016 Jul; 146(7), p. 1373-8.
EPub date: 2016-06-08.
PMID: 27281805
Related Citations
Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study.
Authors: Crous-Bou M.
, Fung T.T.
, Prescott J.
, Julin B.
, Du M.
, Sun Q.
, Rexrode K.M.
, Hu F.B.
, De Vivo I.
.
Source: BMJ (Clinical research ed.), 2014-12-02; 349, p. g6674.
EPub date: 2014-12-02.
PMID: 25467028
Related Citations
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 M.C.
, Hankinson S.E.
, Giovannucci E.
, Kraft P.
, De Vivo I.
.
Source: PloS one, 2013; 8(2), p. e52240.
EPub date: 2013-02-12.
PMID: 23424613
Related Citations
Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study.
Authors: Prescott J.
, Du M.
, Wong J.Y.
, Han J.
, De Vivo I.
.
Source: Human reproduction (Oxford, England), 2012 Dec; 27(12), p. 3622-31.
EPub date: 2012-08-30.
PMID: 22940768
Related Citations
A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus.
Authors: Han J.
, Qureshi A.A.
, Nan H.
, Zhang J.
, Song Y.
, Guo Q.
, Hunter D.J.
.
Source: Cancer research, 2011-03-01; 71(5), p. 1533-9.
EPub date: 2011-01-26.
PMID: 21270109
Related Citations
Polymorphisms in genes involved in oxidative stress and their interactions with lifestyle factors on skin cancer risk.
Authors: He C.
, Qureshi A.A.
, Han J.
.
Source: Journal of dermatological science, 2010 Oct; 60(1), p. 54-6.
EPub date: 2010-07-15.
PMID: 20727719
Related Citations
Polymorphisms of FAS and FAS ligand genes and risk of skin cancer.
Authors: Qureshi A.
, Nan H.
, Dyer M.
, Han J.
.
Source: Journal of dermatological science, 2010 Apr; 58(1), p. 78-80.
EPub date: 2010-01-25.
PMID: 20219325
Related Citations
Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.
Authors: Nan H.
, Kraft P.
, Hunter D.J.
, Han J.
.
Source: International journal of cancer, 2009-08-15; 125(4), p. 909-17.
PMID: 19384953
Related Citations
Polymorphisms in genes involved in DNA repair, cell growth, oxidative stress and inflammatory response, and melanoma risk.
Authors: Gu F.
, Qureshi A.A.
, Kraft P.
, Guo Q.
, Hunter D.J.
, Han J.
.
Source: The British journal of dermatology, 2009 Jul; 161(1), p. 209-12.
EPub date: 2009-05-12.
PMID: 19438866
Related Citations
Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study.
Authors: Nan H.
, Qureshi A.A.
, Hunter D.J.
, Han J.
.
Source: BMC cancer, 2009-06-06; 9, p. 172.
EPub date: 2009-06-06.
PMID: 19500394
Related Citations
A prospective study of telomere length and the risk of skin cancer.
Authors: Han J.
, Qureshi A.A.
, Prescott J.
, Guo Q.
, Ye L.
, Hunter D.J.
, De Vivo I.
.
Source: The Journal of investigative dermatology, 2009 Feb; 129(2), p. 415-21.
EPub date: 2008-07-31.
PMID: 18668136
Related Citations
Missense polymorphisms in matrix metalloproteinase genes and skin cancer risk.
Authors: Nan H.
, Niu T.
, Hunter D.J.
, Han J.
.
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Dec; 17(12), p. 3551-7.
PMID: 19064570
Related Citations
Interleukin and interleukin receptor gene polymorphisms and susceptibility to melanoma.
Authors: Gu F.
, Qureshi A.A.
, Niu T.
, Kraft P.
, Guo Q.
, Hunter D.J.
, Han J.
.
Source: Melanoma research, 2008 Oct; 18(5), p. 330-5.
PMID: 18781131
Related Citations
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 S.E.
, Hu F.B.
, Duffy D.L.
, Zhao Z.Z.
, et al.
.
Source: PLoS genetics, 2008-05-16; 4(5), p. e1000074.
EPub date: 2008-05-16.
PMID: 18483556
Related Citations