Cumulative Association of Five Genetic Variants with Prostate Cancer
S. Lilly Zheng, M.D., Jielin Sun, Ph.D., Fredrik Wiklund, Ph.D., Shelly Smith, M.S., Pär Stattin, M.D., Ph.D., Ge Li, M.D., Hans-Olov Adami, M.D., Ph.D., Fang-Chi Hsu, Ph.D., Yi Zhu, B.S., Katarina Bälter, Ph.D., A. Karim Kader, M.D., Ph.D., Aubrey R. Turner, M.S., Wennuan Liu, Ph.D., Eugene R. Bleecker, M.D., Deborah A. Meyers, Ph.D., David Duggan, Ph.D., John D. Carpten, Ph.D., Bao-Li Chang, Ph.D., William B. Isaacs, Ph.D., Jianfeng Xu, M.D., D.P.H., and Henrik Grönberg, M.D., Ph.D.
Background Single-nucleotide polymorphisms (SNPs) in five chromosomalregions — three at 8q24 and one each at 17q12 and 17q24.3— have been associated with prostate cancer. Each SNPhas only a moderate association, but when SNPs are combined,the association may be stronger.
Methods We evaluated 16 SNPs from five chromosomal regions ina Swedish population (2893 subjects with prostate cancer and1781 control subjects) and assessed the individual and combinedassociation of the SNPs with prostate cancer.
Results Multiple SNPs in each of the five regions were associatedwith prostate cancer in single SNP analysis. When the most significantSNP from each of the five regions was selected and includedin a multivariate analysis, each SNP remained significant afteradjustment for other SNPs and family history. Together, thefive SNPs and family history were estimated to account for 46%of the cases of prostate cancer in the Swedish men we studied.The five SNPs plus family history had a cumulative associationwith prostate cancer (P for trend, 3.93x10–28). In menwho had any five or more of these factors associated with prostatecancer, the odds ratio for prostate cancer was 9.46 (P=1.29x10–8),as compared with men without any of the factors. The cumulativeeffect of these variants and family history was independentof serum levels of prostate-specific antigen at diagnosis.
Conclusions SNPs in five chromosomal regions plus a family historyof prostate cancer have a cumulative and significant associationwith prostate cancer.
Source Information
From the Center for Human Genomics (S.L.Z., J.S., S.S., G.L., F.-C.H., Y.Z., A.R.T., W.L., E.R.B., D.A.M., B.-L.C., J.X.) and the Departments of Biostatistical Sciences (F.-C.H.) and Urology (A.K.K.), Wake Forest University School of Medicine, Winston-Salem, NC; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (F.W., H.-O.A., K.B., H.G.); the Department of Urology, Umeå University Hospital, Umeå, Sweden (P.S.); the Department of Epidemiology, Harvard School of Public Health, Boston (H.-O.A.); Translational Genomics Research Institute, Phoenix, AZ (D.D., J.D.C.); and Johns Hopkins Medical Institutions, Baltimore (W.B.I.). This article (10.1056/NEJMoa075819) was published at www.nejm.org on January 16, 2008.
Address reprint requests to Dr. Xu at the Center for Human Genomics, Medical Center Blvd., Winston-Salem, NC 27157, or at jxu{at}wfubmc.edu; or to Dr. Isaacs at Marburg 115, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287, or at wisaacs{at}jhmi.edu.
Five Genetic Variants Associated with Prostate Cancer
Coates R. J., Khoury M. J., Gwinn M., Gartner C. E., Barendregt J. J., Hall W. D., Janssens A. C. J.W., van Duijn C. M., Severi G., Byrnes G. B., Hopper J. L., Thorat M. A., Vickers A., Lilja H., Scardino P., Eisinger F., Xu J., Isaacs W. B., Grönberg H.
Extract |
Full Text |
PDF
N Engl J Med 2008;
358:2738-2741, Jun 19, 2008.
Correspondence
This article has been cited by other articles:
Li, J., Coates, R. J., Gwinn, M., Khoury, M. J.
(2009). Steroid 5-{alpha}-Reductase Type 2 (SRD5a2) Gene Polymorphisms and Risk of Prostate Cancer: A HuGE Review. Am J Epidemiol
0: kwp318v1-kwp318
[Abstract][Full Text]
Middeldorp, A., Jagmohan-Changur, S., van Eijk, R., Tops, C., Devilee, P., Vasen, H. F. A., Hes, F. J., Houlston, R., Tomlinson, I., Houwing-Duistermaat, J. J., Wijnen, J. T., Morreau, H., van Wezel, T.
(2009). Enrichment of Low Penetrance Susceptibility Loci in a Dutch Familial Colorectal Cancer Cohort. Cancer Epidemiol. Biomarkers Prev.
18: 3062-3067
[Abstract][Full Text]
McClure, A., Lunt, M., Eyre, S., Ke, X., Thomson, W., Hinks, A., Bowes, J., Gibbons, L., Plant, D., Wilson, A. G., Marinou, I., Morgan, A. W., Emery, P., BIRAC consortium, , Steer, S., Hocking, L. J., Reid, D. M., Wordsworth, P., Harrison, P., Worthington, J., Barton, A.
(2009). Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci. Rheumatology (Oxford)
48: 1369-1374
[Abstract][Full Text]
Young, R P, Hopkins, R J, Hay, B A, Epton, M J, Mills, G D, Black, P N, Gardner, H D, Sullivan, R, Gamble, G D
(2009). A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers. Postgrad. Med. J.
85: 515-524
[Abstract][Full Text]
KLEIN, E. A.
(2009). What's new in prostate cancer screening and prevention?. Cleveland Clinic Journal of Medicine
76: 439-445
[Abstract][Full Text]
Mayne, S. T., Gruber, S. B.
(2009). Emerging Molecular Technologies for Identifying the Risk of Second Cancers. Cancer Prevention Research
2: 605-607
[Full Text]
Zheng, S. L., Stevens, V. L., Wiklund, F., Isaacs, S. D., Sun, J., Smith, S., Pruett, K., Wiley, K. E., Kim, S.-T., Zhu, Y., Zhang, Z., Hsu, F.-C., Turner, A. R., Johansson, J.-E., Liu, W., Kim, J. W., Chang, B.-L., Duggan, D., Carpten, J., Rodriguez, C., Isaacs, W., Gronberg, H., Xu, J.
(2009). Two Independent Prostate Cancer Risk-Associated Loci at 11q13. Cancer Epidemiol. Biomarkers Prev.
18: 1815-1820
[Abstract][Full Text]
Concato, J., Jain, D., Uchio, E., Risch, H., Li, W. W., Wells, C. K.
(2009). Molecular Markers and Death From Prostate Cancer. ANN INTERN MED
150: 595-603
[Abstract][Full Text]
Wiklund, F. E., Adami, H.-O., Zheng, S. L., Stattin, P., Isaacs, W. B., Gronberg, H., Xu, J.
(2009). Established Prostate Cancer Susceptibility Variants are not Associated with Disease Outcome. Cancer Epidemiol. Biomarkers Prev.
18: 1659-1662
[Abstract][Full Text]
Pan, J., Lin, J., Izzo, J. G., Liu, Y., Xing, J., Huang, M., Ajani, J. A., Wu, X.
(2009). Genetic susceptibility to esophageal cancer: the role of the nucleotide excision repair pathway. Carcinogenesis
30: 785-792
[Abstract][Full Text]
FitzGerald, L. M., Kwon, E. M., Koopmeiners, J. S., Salinas, C. A., Stanford, J. L., Ostrander, E. A.
(2009). Analysis of Recently Identified Prostate Cancer Susceptibility Loci in a Population-based Study: Associations with Family History and Clinical Features. Clin. Cancer Res.
15: 3231-3237
[Abstract][Full Text]
Penney, K. L., Salinas, C. A., Pomerantz, M., Schumacher, F. R., Beckwith, C. A., Lee, G.-S., Oh, W. K., Sartor, O., Ostrander, E. A., Kurth, T., Ma, J., Mucci, L., Stanford, J. L., Kantoff, P. W., Hunter, D. J., Stampfer, M. J., Freedman, M. L.
(2009). Evaluation of 8q24 and 17q Risk Loci and Prostate Cancer Mortality. Clin. Cancer Res.
15: 3223-3230
[Abstract][Full Text]
Chang, B.-L., Cramer, S. D., Wiklund, F., Isaacs, S. D., Stevens, V. L., Sun, J., Smith, S., Pruett, K., Romero, L. M., Wiley, K. E., Kim, S.-T., Zhu, Y., Zhang, Z., Hsu, F.-C., Turner, A. R., Adolfsson, J., Liu, W., Kim, J. W., Duggan, D., Carpten, J., Zheng, S. L., Rodriguez, C., Isaacs, W. B., Gronberg, H., Xu, J.
(2009). Fine mapping association study and functional analysis implicate a SNP in MSMB at 10q11 as a causal variant for prostate cancer risk. Hum Mol Genet
18: 1368-1375
[Abstract][Full Text]
Hsu, F.-C., Sun, J., Wiklund, F., Isaacs, S. D., Wiley, K. E., Purcell, L. D., Gao, Z., Stattin, P., Zhu, Y., Kim, S.-T., Zhang, Z., Liu, W., Chang, B.-L., Walsh, P. C., Duggan, D., Carpten, J. D., Isaacs, W. B., Gronberg, H., Xu, J., Zheng, S. L.
(2009). A Novel Prostate Cancer Susceptibility Locus at 19q13. Cancer Res.
69: 2720-2723
[Abstract][Full Text]
Nam, R. K., Zhang, W. W., Trachtenberg, J., Seth, A., Klotz, L. H., Stanimirovic, A., Punnen, S., Venkateswaran, V., Toi, A., Loblaw, D. A., Sugar, L., Siminovitch, K. A., Narod, S. A.
(2009). Utility of Incorporating Genetic Variants for the Early Detection of Prostate Cancer. Clin. Cancer Res.
15: 1787-1793
[Abstract][Full Text]
Zheng, S. L., Sun, J., Wiklund, F., Gao, Z., Stattin, P., Purcell, L. D., Adami, H.-O., Hsu, F.-C., Zhu, Y., Adolfsson, J., Johansson, J.-E., Turner, A. R., Adams, T. S., Liu, W., Duggan, D., Carpten, J. D., Chang, B.-L., Isaacs, W. B., Xu, J., Gronberg, H.
(2009). Genetic Variants and Family History Predict Prostate Cancer Similar to Prostate-Specific Antigen. Clin. Cancer Res.
15: 1105-1111
[Abstract][Full Text]
Agalliu, I., Gern, R., Leanza, S., Burk, R. D.
(2009). Associations of High-Grade Prostate Cancer with BRCA1 and BRCA2 Founder Mutations. Clin. Cancer Res.
15: 1112-1120
[Abstract][Full Text]
Attia, J., Ioannidis, J. P. A., Thakkinstian, A., McEvoy, M., Scott, R. J., Minelli, C., Thompson, J., Infante-Rivard, C., Guyatt, G.
(2009). How to Use an Article About Genetic Association: C: What Are the Results and Will They Help Me in Caring for My Patients?. JAMA
301: 304-308
[Abstract][Full Text]
Ioannidis, J. P.A.
(2009). Personalized Genetic Prediction: Too Limited, Too Expensive, or Too Soon?. ANN INTERN MED
150: 139-141
[Full Text]
Gann, P. H.
(2009). Randomized Trials of Antioxidant Supplementation for Cancer Prevention: First Bias, Now Chance--Next, Cause. JAMA
301: 102-103
[Full Text]
Sun, J., Zheng, S. L., Wiklund, F., Isaacs, S. D., Li, G., Wiley, K. E., Kim, S.-T., Zhu, Y., Zhang, Z., Hsu, F.-C., Turner, A. R., Stattin, P., Liu, W., Kim, J. W., Duggan, D., Carpten, J., Isaacs, W., Gronberg, H., Xu, J., Chang, B.-L.
(2009). Sequence Variants at 22q13 Are Associated with Prostate Cancer Risk. Cancer Res.
69: 10-15
[Abstract][Full Text]
Park, S. L., Chang, S.-C., Cai, L., Cordon-Cardo, C., Ding, B.-G., Greenland, S., Hussain, S. K., Jiang, Q., Liu, S., Lu, M.-L., Mao, J. T., Morgenstern, H., Mu, L.-N., Ng, L. J., Pantuck, A., Rao, J., Reuter, V. E., Tashkin, D. P., You, N.-C. Y., Yu, C.-Q., Yu, S.-Z., Zhao, J.-K., Belldegrun, A., Zhang, Z.-F.
(2008). Associations between Variants of the 8q24 Chromosome and Nine Smoking-Related Cancer Sites. Cancer Epidemiol. Biomarkers Prev.
17: 3193-3202
[Abstract][Full Text]
Khoury, M. J., Valdez, R., Albright, A.
(2008). Public Health Genomics Approach to Type 2 Diabetes. Diabetes
57: 2911-2914
[Full Text]
Janssens, A. C. J.W., van Duijn, C. M.
(2008). Genome-based prediction of common diseases: advances and prospects. Hum Mol Genet
17: R166-R173
[Abstract][Full Text]
Easton, D. F., Eeles, R. A.
(2008). Genome-wide association studies in cancer. Hum Mol Genet
17: R109-R115
[Abstract][Full Text]
Lindstrom, S., Adami, H.-O., Adolfsson, J., Wiklund, F.
(2008). Y Chromosome Haplotypes and Prostate Cancer in Sweden. Clin. Cancer Res.
14: 6712-6716
[Abstract][Full Text]
Xu, J., Isaacs, S. D., Sun, J., Li, G., Wiley, K. E., Zhu, Y., Hsu, F.-C., Wiklund, F., Turner, A. R., Adams, T. S., Liu, W., Trock, B. J., Partin, A. W., Chang, B., Walsh, P. C., Gronberg, H., Isaacs, W., Zheng, S.
(2008). Association of Prostate Cancer Risk Variants with Clinicopathologic Characteristics of the Disease. Clin. Cancer Res.
14: 5819-5824
[Abstract][Full Text]
Koppelman, G. H., te Meerman, G. J., Postma, D. S.
(2008). Genetic testing for asthma. Eur Respir J
32: 775-782
[Abstract][Full Text]
Levin, A. M., Machiela, M. J., Zuhlke, K. A., Ray, A. M., Cooney, K. A., Douglas, J. A.
(2008). Chromosome 17q12 Variants Contribute to Risk of Early-Onset Prostate Cancer. Cancer Res.
68: 6492-6495
[Abstract][Full Text]
Ostrander, E. A., Udler, M. S.
(2008). The Role of the BRCA2 Gene in Susceptibility to Prostate Cancer Revisited. Cancer Epidemiol. Biomarkers Prev.
17: 1843-1848
[Abstract][Full Text]
Murray, S. S., Topol, E. J.
(2008). Gaining Insights in Coronary Disease Genomics. J Am Coll Cardiol
52: 385-386
[Full Text]
Gail, M. H.
(2008). Discriminatory Accuracy From Single-Nucleotide Polymorphisms in Models to Predict Breast Cancer Risk. JNCI J Natl Cancer Inst
100: 1037-1041
[Abstract][Full Text]
Vergeer, M., El-Harchaoui, K., Stroes, E. S.G., Tiret, L., Tregouet, D.-A., Cambien, F., Kathiresan, S., Newton-Cheh, C., Orho-Melander, M.
(2008). Cholesterol Gene Polymorphisms and Cardiovascular Events. NEJM
359: 92-93
[Full Text]
Coates, R. J., Khoury, M. J., Gwinn, M., Gartner, C. E., Barendregt, J. J., Hall, W. D., Janssens, A. C. J.W., van Duijn, C. M., Severi, G., Byrnes, G. B., Hopper, J. L., Thorat, M. A., Vickers, A., Lilja, H., Scardino, P., Eisinger, F., Xu, J., Isaacs, W. B., Gronberg, H.
(2008). Five Genetic Variants Associated with Prostate Cancer. NEJM
358: 2738-2741
[Full Text]
Gelmann, E. P.
(2008). Complexities of Prostate-Cancer Risk. NEJM
358: 961-963
[Full Text]
Previous
