Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis

BMC Cancer

Norihiko Tsuchiya⁵  Shintaro Narita⁵  Takamitsu Inoue⁵  Mitsuru Saito⁵  Kazuyuki Numakura⁵  Mingguo Huang⁵  Shingo Hatakeyama²  Shigeru Satoh⁵  Seiichi Saito¹  Chikara Ohyama²  Yoichi Arai³  Osamu Ogawa⁴  Tomonori Habuchi⁵ 

[1] Division of Urology, Department of Organ-oriented Medicine, University of the Ryukyu, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan

[2] Department of Urology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan

[3] Department of Urology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

[4] Department of Urology, Graduate School of Medicine, Kyoto University, 54 Syogoin-kawaramachi, Sakyo-ku, Kyoto, 606-8507, Japan

[5] Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan

关键词: Insulin-like growth factor-1;    Polymorphism;    Survival;    Bone metastasis;    Prostate cancer;   

Others  :  1079840
DOI  :  10.1186/1471-2407-13-150

 received in 2012-11-27, accepted in 2013-03-18,  发布年份 2013

【 摘 要 】

Background

The insulin-like growth factor-1 (IGF-1) plays an important role in growth of prostate cancer (PCa) cells and facilitating the development and progression of PCa. This study aimed to evaluate the association of polymorphisms in three linkage disequilibrium (LD) blocks of the IGF-1 on the survival of metastatic PCa patients.

Methods

A total of 215 patients with bone metastases at initial presentation were included in this study. The cytosine-adenine (CA) repeat polymorphism and rs12423791 were selected as representative polymorphisms in the LD blocks 1 and 2, respectively. Haplotype in the LD block 3 was analyzed using two tag single nucleotide polymorphisms (SNPs), rs6220 and rs7136446. Cancer-specific survival rate was estimated from the Kaplan-Meier curve, and the survival data were compared using the log-rank test.

Results

Cancer-specific survival was significantly associated with the CA repeat polymorphism, rs12423791, and rs6220 (P = 0.013, 0.014, and 0.014, respectively). Although rs7136446 had no significant association with survival, the haplotype in the LD block 3 was significantly associated with cancer-specific survival (P = 0.0003). When the sum of the risk genetic factors in each LD block (19-repeat allele, C allele of rs12423791, or C-T haplotype) was considered, patients with all the risk factors had significantly shorter cancer specific-survival than those with 0–2 risk factors (P = 0.0003).

Conclusions

Polymorphisms in the IGF-1, especially a haplotype in the LD block 3, are assumed to be genetic markers predicting the outcome of metastatic PCa.

【 授权许可】

   
2013 Tsuchiya et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Resnick MI, Grayhack JT: Treatment of stage IV carcinoma of the prostate. Urol Clin North Am 1975, 2(1):141-161.
• [2]de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F: Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011, 364(21):1995-2005.
• [3]Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J: Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. Lancet 2010, 375(9724):1437-1446.
• [4]de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010, 376(9747):1147-1154.
• [5]Soloway MS, Hardeman SW, Hickey D, Raymond J, Todd B, Soloway S, Moinuddin M: Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 1988, 61(1):195-202.
• [6]Merrick MV, Ding CL, Chisholm GD, Elton RA: Prognostic significance of alkaline and acid phosphatase and skeletal scintigraphy in carcinoma of the prostate. Br J Urol 1985, 57(6):715-720.
• [7]Fossa SD, Paus E, Lindegaard M, Newling DW: Prostate-specific antigen and other prognostic factors in patients with hormone-resistant prostatic cancer undergoing experimental treatment. Br J Urol 1992, 69(2):175-179.
• [8]Cooper EH, Armitage TG, Robinson MR, Newling DW, Richards BR, Smith PH, Denis L, Sylvester R: Prostatic specific antigen and the prediction of prognosis in metastatic prostatic cancer. Cancer 1990, 66(5 Suppl):1025-1028.
• [9]Yang M, Xie W, Mostaghel E, Nakabayashi M, Werner L, Sun T, Pomerantz M, Freedman M, Ross R, Regan M: SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clinical Oncol: Official Journal of The American Society of Clinical Oncology 2011, 29(18):2565-2573.
• [10]Tsuchiya N, Wang L, Suzuki H, Segawa T, Fukuda H, Narita S, Shimbo M, Kamoto T, Mitsumori K, Ichikawa T: Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer. J Clin Oncol 2006, 24(13):1982-1989.
• [11]Penney KL, Pyne S, Schumacher FR, Sinnott JA, Mucci LA, Kraft PL, Ma J, Oh WK, Kurth T, Kantoff PW: Genome-wide association study of prostate cancer mortality. Cancer Epidemiol Biomarkers Prev 2010, 19(11):2869-2876.
• [12]Lin DW, FitzGerald LM, Fu R, Kwon EM, Zheng SL, Kolb S, Wiklund F, Stattin P, Isaacs WB, Xu J: Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality. Cancer Epidemiol Biomarkers Prev 2011, 20(9):1928-1936.
• [13]Wu JD, Odman A, Higgins LM, Haugk K, Vessella R, Ludwig DL, Plymate SR: In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors. Clinical Cancer Res: an Official Journal of the American Association for Cancer Research 2005, 11(8):3065-3074.
• [14]Montagnani Marelli M, Moretti RM, Procacci P, Motta M, Limonta P: Insulin-like growth factor-I promotes migration in human androgen-independent prostate cancer cells via the alphavbeta3 integrin and PI3-K/Akt signaling. Int J Oncol 2006, 28(3):723-730.
• [15]Rowlands MA, Holly JM, Gunnell D, Donovan J, Lane JA, Hamdy F, Neal DE, Oliver S, Smith GD, Martin RM: Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case–control study ProtecT. Cancer Res 2012, 72(2):503-515.
• [16]Harrela M, Koistinen H, Kaprio J, Lehtovirta M, Tuomilehto J, Eriksson J, Toivanen L, Koskenvuo M, Leinonen P, Koistinen R: Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3. J Clin Invest 1996, 98(11):2612-2615.
• [17]Key TJ, Appleby PN, Reeves GK, Roddam AW: Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010, 11(6):530-542.
• [18]Rinaldi S, Cleveland R, Norat T, Biessy C, Rohrmann S, Linseisen J, Boeing H, Pischon T, Panico S, Agnoli C: Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. International Journal of Cancer Journal international du cancer 2010, 126(7):1702-1715.
• [19]Tsuchiya N, Wang L, Horikawa Y, Inoue T, Kakinuma H, Matsuura S, Sato K, Ogawa O, Kato T, Habuchi T: CA repeat polymorphism in the insulin-like growth factor-I gene is associated with increased risk of prostate cancer and benign prostatic hyperplasia. Int J Oncol 2005, 26(1):225-231.
• [20]Chan JM, Stampfer MJ, Ma J, Gann P, Gaziano JM, Pollak M, Giovannucci E: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J Natl Cancer Inst 2002, 94(14):1099-1106.
• [21]Jernstrom H, Chu W, Vesprini D, Tao Y, Majeed N, Deal C, Pollak M, Narod SA: Genetic factors related to racial variation in plasma levels of insulin-like growth factor-1: implications for premenopausal breast cancer risk. Mol Genet Metab 2001, 72(2):144-154.
• [22]Rosen CJ, Kurland ES, Vereault D, Adler RA, Rackoff PJ, Craig WY, Witte S, Rogers J, Bilezikian JP: Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab 1998, 83(7):2286-2290.
• [23]Chen X, Guan J, Song Y, Chen P, Zheng H, Tang C, Wu Q: IGF-I (CA) repeat polymorphisms and risk of cancer: a meta-analysis. J Hum Genet 2008, 53(3):227-238.
• [24]Cheng I, Stram DO, Penney KL, Pike M, Le Marchand L, Kolonel LN, Hirschhorn J, Altshuler D, Henderson BE, Freedman ML: Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort. J Natl Cancer Inst 2006, 98(2):123-134.
• [25]Johansson M, McKay JD, Stattin P, Canzian F, Boillot C, Wiklund F, Adami HO, Balter K, Gronberg H, Kaaks R: Comprehensive evaluation of genetic variation in the IGF1 gene and risk of prostate cancer. International Journal of Cancer Journal International du cancer 2007, 120(3):539-542.
• [26]Verheus M, McKay JD, Kaaks R, Canzian F, Biessy C, Johansson M, Grobbee DE, Peeters PH, van Gils CH: Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density. Breast Cancer Res Treat 2008, 112(1):109-122.
• [27]Johansson M, McKay JD, Wiklund F, Rinaldi S, Verheus M, van Gils CH, Hallmans G, Balter K, Adami HO, Gronberg H: Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels. J Clin Endocrinol Metab 2007, 92(12):4820-4826.
• [28]Consortium: IH: A haplotype map of the human genome. Nature 2005, 437(7063):1299-1320.
• [29]Fletcher O, Gibson L, Johnson N, Altmann DR, Holly JM, Ashworth A, Peto J, Silva Idos S: Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2005, 14(1):2-19.
• [30]Patel AV, Cheng I, Canzian F, Le Marchand L, Thun MJ, Berg CD, Buring J, Calle EE, Chanock S, Clavel-Chapelon F: IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3). PLoS One 2008, 3(7):e2578.
• [31]Al-Zahrani A, Sandhu MS, Luben RN, Thompson D, Baynes C, Pooley KA, Luccarini C, Munday H, Perkins B, Smith P: IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet 2006, 15(1):1-10.
• [32]Tae HJ, Luo X, Kim KH: Roles of CCAAT/enhancer-binding protein and its binding site on repression and derepression of acetyl-CoA carboxylase gene. J Biol Chem 1994, 269(14):10475-10484.
• [33]Missmer SA, Haiman CA, Hunter DJ, Willett WC, Colditz GA, Speizer FE, Pollak MN, Hankinson SE: A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer. International journal of cancer Journal international du cancer 2002, 100(3):332-336.
• [34]Chen HY, Chan IH, Sham AL, Leung VH, Ma SL, Ho SC, Tang NL: Haplotype effect in the IGF1 promoter accounts for the association between microsatellite and serum IGF1 concentration. Clin Endocrinol 2011, 74(4):520-527.
• [35]Qu BH, Karas M, Koval A, LeRoith D: Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced cell proliferation. J Biol Chem 1999, 274(44):31179-31184.
• [36]Parrizas M, Saltiel AR, LeRoith D: Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. J Biol Chem 1997, 272(1):154-161.
• [37]Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, Bartsch G, Klocker H: Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 1994, 54(20):5474-5478.
• [38]Rubin J, Ackert-Bicknell CL, Zhu L, Fan X, Murphy TC, Nanes MS, Marcus R, Holloway L, Beamer WG, Rosen CJ: IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo. J Clin Endocrinol Metab 2002, 87(9):4273-4279.