Background. Prostate cancer (PCa) racial disparity is multifactorial, involving biological, sociocultural, and lifestyle determinants. We investigated the association between selected potentially functional polymorphisms (SNPs) and prostate cancer (PCa) risk in Black (AAM) and White (EAM) men. We further explored if these associations varied by the body mass index (BMI) and height. Methods. Age-matched DNA samples from 259 AAM and 269 EAM were genotyped for 10 candidate SNPs in 7 genes using the TaqMan allelic differentiation analysis. The dominant, recessive, and additive age-adjusted unconditional logistic regression models were fitted. Results. Three SNPs showed statistically significant associations with PCa risk: in AAM, HNF1B rs7501939 ( , ) and rs4430796 ( , ); in EAM, CTBP2 rs4962416 ( , ). In addition, high BMI in AAM ( , ) and height in EAM ( , ) showed significant associations. Interestingly, HNF1B rs7501939 was associated with PCa exclusively in obese AAM ( , ). Conclusion. Our results suggest that variation in the HNF1B may influence PCa risk in obese AAM. 1. Introduction Prostate cancer (PCa) remains the most common type of solid malignancy and the second-leading cause of all cancer death in US men [1]. However, the burden of PCa is not the same across all racial and ethnic groups, as African American/Black men (AAM) consistently demonstrate 1.6 times higher incidence and 2-3 times higher mortality rates of PCa, compared to their nonhispanic white (EAM) counterparts [2]. In addition, AAM are more likely to be diagnosed at an earlier age and have more aggressive tumors and higher recurrence rates following definite treatments [2, 3]. The etiology of racial disparity in PCa is thought to be multifactorial, involving biological, sociocultural, and lifestyle determinants [4]. Although genome-wide association studies (GWAS) have identified more than a dozen PCa risk loci [5], elucidating the biological basis for these associations is challenging [6]. Identified risk loci include the noncoding variants, such as those located in the 8q24 region [7], as well as polymorphisms in the coding regions (genes) that either alter, or are predicted to alter, the protein expression (such as HNF1B [8], TERT [5], and RNASEL [9]). The post-GWAS studies are increasingly suggestive of the interaction between genetic variants and environmental risk factors [10] for which our understanding is still largely inadequate [11]. Established risk factors for PCa are increasing age, race, and family history of the disease [2–4]. Obesity (which affects 35% of all US adults
References
[1]
American Cancer Society, Cancer Facts & Figures for African Americans 2011-2012, American Cancer Society, Atlanta, Ga, USA, 2011.
[2]
G. Chornokur, K. Dalton, M. E. Borysova, and N. B. Kumar, “Disparities at presentation, diagnosis, treatment, and survival in African American men, affected by prostate cancer,” Prostate, vol. 71, no. 9, pp. 985–997, 2011.
[3]
I. J. Powell, “Epidemiology and pathophysiology of prostate cancer in African-American men,” Journal of Urology, vol. 177, no. 2, pp. 444–449, 2007.
[4]
E. D. Crawford, “Epidemiology of prostate cancer,” Urology, vol. 62, no. 6, pp. 3–12, 2003.
[5]
Z. Kote-Jarai, A. A. A. Olama, G. G. Giles et al., “Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study,” Nature Genetics, vol. 43, no. 8, pp. 785–791, 2011.
[6]
M. L. Freedman, A. N. A. Monteiro, S. A. Gayther et al., “Principles for the post-GWAS functional characterization of cancer risk loci,” Nature Genetics, vol. 43, no. 6, pp. 513–518, 2011.
[7]
C. A. Haiman, N. Patterson, M. L. Freedman et al., “Multiple regions within 8q24 independently affect risk for prostate cancer,” Nature Genetics, vol. 39, no. 5, pp. 638–644, 2007.
[8]
V. L. Stevens, J. Ahn, J. Sun et al., “HNFIB and JAZFI genes, diabetes, and prostate cancer risk,” Prostate, vol. 70, no. 6, pp. 601–607, 2010.
[9]
M. M. Shen and C. Abate-Shen, “Molecular genetics of prostate cancer: new prospects for old challenges,” Genes and Development, vol. 24, no. 18, pp. 1967–2000, 2010.
[10]
C. Kooperberg, M. LeBlanc, J. Y. Dai, and I. Rajapakse, “Structures and assumptions: strategies to harness gene × gene and gene × environment interactions in GWAS,” Statistical Science, vol. 24, no. 4, pp. 472–488, 2009.
[11]
M. C. Cornelis, A. Agrawal, J. W. Cole et al., “The gene, environment association studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions,” Genetic Epidemiology, vol. 34, no. 4, pp. 364–372, 2010.
[12]
D. S. Michaud, K. Augustsson, E. B. Rimm, M. J. Stampfer, W. C. Willet, and E. Giovannucci, “A prospective study on intake of animal products and risk of prostate cancer,” Cancer Causes and Control, vol. 12, no. 6, pp. 557–567, 2001.
[13]
R. Sinha, Y. Park, B. I. Graubard et al., “Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States,” American Journal of Epidemiology, vol. 170, no. 9, pp. 1165–1177, 2009.
[14]
E. L. Giovannucci, Y. Liu, M. F. Leitzmann, M. J. Stampfer, and W. C. Willett, “A prospective study of physical activity and incident and fatal prostate cancer,” Archives of Internal Medicine, vol. 165, no. 9, pp. 1005–1010, 2005.
[15]
C. M. Friedenreich and I. Thune, “A review of physical activity and prostate cancer risk,” Cancer Causes and Control, vol. 12, no. 5, pp. 461–475, 2001.
[16]
C. M. Friedenreich, S. E. McGregor, K. S. Courneya, S. J. Angyalfi, and F. G. Elliott, “Case-control study of lifetime total physical activity and prostate cancer risk,” American Journal of Epidemiology, vol. 159, no. 8, pp. 740–749, 2004.
[17]
S. J. Freedland and E. A. Platz, “Obesity and prostate cancer: making sense out of apparently conflicting data,” Epidemiologic Reviews, vol. 29, no. 1, pp. 88–97, 2007.
[18]
C. L. Ogden, M. M. Lamb, M. D. Carroll, and K. M. Flegal, “Obesity and socioeconomic status in adults: United States, 2005–2008,” NCHS Data Brief, no. 50, pp. 1–8, 2010.
[19]
CDC, Health United States, 2011, 2012, http://www.cdc.gov/nchs/data/hus/hus11.pdf.
[20]
M. A. Kirschner, N. Ertel, and G. Schneider, “Obesity, hormones, and cancer,” Cancer Research, vol. 41, no. 9, pp. 3711–3717, 1981.
[21]
A. G. Renehan, M. Tyson, M. Egger, R. F. Heller, and M. Zwahlen, “Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies,” The Lancet, vol. 371, no. 9612, pp. 569–578, 2008.
[22]
K. M. Waters, L. Le Marchand, L. N. Kolonel et al., “Generalizability of associations from prostate cancer genome-wide association studies in multiple populations,” Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 4, pp. 1285–1289, 2009.
[23]
R. A. Eeles, Z. Kote-Jarai, G. G. Giles, et al., “Multiple newly identified loci associated with prostate cancer susceptibility,” Nature Genetics, vol. 40, no. 3, pp. 316–321, 2008.
[24]
J. Gudmundsson, P. Sulem, V. Steinthorsdottir et al., “Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes,” Nature Genetics, vol. 39, no. 8, pp. 977–983, 2007.
[25]
H. Liu, B. Wang, and C. Han, “Meta-analysis of genome-wide and replication association studies on prostate cancer,” Prostate, vol. 71, no. 2, pp. 209–224, 2011.
[26]
J. Sun, L. Purcell, Z. Gao et al., “Association between sequence variants at 17q12 and 17q24.3 and prostate cancer risk in European and African Americans,” Prostate, vol. 68, no. 7, pp. 691–697, 2008.
[27]
J. Ahn, A. S. Kibel, J. Y. Park et al., “Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence,” Clinical Cancer Research, vol. 17, no. 5, pp. 1075–1081, 2011.
[28]
B.-L. Chang, E. Spangler, S. Gallagher et al., “Validation of genome-wide prostate cancer associations in men of african descent,” Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 1, pp. 23–32, 2011.
[29]
C. A. Haiman, G. K. Chen, W. J. Blot et al., “Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans,” PLoS Genetics, vol. 7, no. 5, Article ID e1001387, 2011.
[30]
S. Hooker, W. Hernandez, H. Chen et al., “Replication of prostate cancer risk loci on 8q24, 11q13, 17q12, 19q33, and Xp11 in African Americans,” Prostate, vol. 70, no. 3, pp. 270–275, 2010.
[31]
S. Lindstrom, F. Schumacher, A. Siddiq et al., “Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers-results from BPC3,” PLoS ONE, vol. 6, no. 2, Article ID e17142, 2011.
[32]
A. W. Hsing, L. C. Sakoda, and S. Chua Jr., “Obesity, metabolic syndrome, and prostate cancer,” The American Journal of Clinical Nutrition, vol. 86, no. 3, pp. s843–s857, 2007.
[33]
C. Bingham and A. T. Hattersley, “Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1β,” Nephrology Dialysis Transplantation, vol. 19, no. 11, pp. 2703–2708, 2004.
[34]
I. S. Haldorsen, M. Vesterhus, H. R？der et al., “Lack of pancreatic body and tail in HNF1B mutation carriers,” Diabetic Medicine, vol. 25, no. 7, pp. 782–787, 2008.
[35]
M. Nakayama, K. Nozu, Y. Goto et al., “HNF1B alterations associated with congenital anomalies of the kidney and urinary tract,” Pediatric Nephrology, vol. 25, no. 6, pp. 1073–1079, 2010.
[36]
S. I. Berndt, J. Sampson, M. Yeager et al., “Large-scale fine mapping of the HNF1B locus and prostate cancer risk,” Human Molecular Genetics, vol. 20, no. 16, pp. 3322–3329, 2011.
[37]
J. Sun, S. L. Zheng, F. Wiklund et al., “Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12,” Nature Genetics, vol. 40, no. 10, pp. 1153–1155, 2008.
[38]
V. W. Setiawan, J. Haessler, F. Schumacher et al., “HNF1B and endometrial cancer risk: results from the page study,” PLoS ONE, vol. 7, no. 1, Article ID e30390, 2012.
[39]
A. B. Spurdle, D. J. Thompson, S. Ahmed et al., “Genome-wide association study identifies a common variant associated with risk of endometrial cancer,” Nature Genetics, vol. 43, no. 5, pp. 451–455, 2011.
[40]
L. W. Harries, J. R. B. Perry, P. McCullagh, and M. Crundwell, “Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer,” BMC Cancer, vol. 10, article 315, 2010.
[41]
E. Weiderpass, W. Ye, H. Vainio, R. Kaaks, and H.-O. Adami, “Reduced risk of prostate cancer among patients with diabetes mellitus,” International Journal of Cancer, vol. 102, no. 3, pp. 258–261, 2002.
[42]
P. Berstad, R. J. Coates, L. Bernstein et al., “A case-control study of body mass index and breast cancer risk in white and African-American women,” Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 6, pp. 1532–1544, 2010.
[43]
M. Sarkissyan, Y. Wu, and J. V. Vadgama, “Obesity is associated with breast cancer in African-American women but not Hispanic women in South Los Angeles,” Cancer, vol. 117, no. 16, pp. 3814–3823, 2011.
[44]
S. Paliwal, R. C. Kovi, B. Nath, Y.-W. Chen, B. C. Lewis, and S. R. Grossman, “The alternative reading frame tumor suppressor antagonizes hypoxia-induced cancer cell migration via interaction with the COOH-terminal binding protein corepressor,” Cancer Research, vol. 67, no. 19, pp. 9322–9329, 2007.
[45]
G. Thomas, K. B. Jacobs, M. Yeager et al., “Multiple loci identified in a genome-wide association study of prostate cancer,” Nature Genetics, vol. 40, no. 3, pp. 310–315, 2008.
