Skip to main content
Top
Published in: Tumor Biology 11/2014

01-11-2014 | Research Article

Genetic variations of CAV1 gene contribute to HCC risk: a case–control study

Authors: Xixue Zhao, Guozheng Pan, Qingzhong Yuan, Dongpo Mu, Jun Zhang, Tao Cui, Jian Zhang, Linghai Zhang

Published in: Tumor Biology | Issue 11/2014

Login to get access

Abstract

Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common cause of cancer mortality worldwide. However, the exact molecular mechanism of HCC remains uncertain. Caveolin-1 (CAV1) is the main protein in the caveolin family and plays an important role in tumorigenesis signaling. However, the contribution of CAV1 genetic variants to HCC is still unknown. The purpose of this study was to evaluate the association between the tagSNPs of the CAV1 gene and HCC risk. In this case–control study, we enrolled 1,000 HCC patients and 1,000 cancer-free controls, which were frequency-matched by age, gender, and HBV infection status. We found that CAV1 rs729949 was statistically associated with increased risk of HCC (odds ratio (OR) = 1.28; 95 % confidence interval (CI), 1.11–1.48; P = 8.53 × 10−4), even after Bonferroni correction (P = 5.97 × 10−3); the expression levels of CAV1 in cancer tissues were significantly lower than those in adjacent normal tissues (P = 0.012). We also detected a significant association for CAV1 rs3807989 under the log-additive model (OR = 0.85; 95 % CI, 0.74–0.98; P = 0.026). Significant associations were also detected for CAV1 rs6466583 (GG vs AA: OR = 2.53; 95 % CI, 1.24–5.17; P = 0.011) and CAV1 rs3807986 (AG vs AA: OR = 3.16; 95 % CI, 1.68–5.91; P = 3.36 × 10−4) among genotype comparisons. These findings indicated that genetic variants n CAV1 might contribute to HCC susceptibility.
Literature
1.
go back to reference Long XD, Zhao D, Wang C, Huang XY, Yao JG, Ma Y, et al. Genetic polymorphisms in DNA repair genes XRCC4 and XRCC5 and aflatoxin b1-related hepatocellular carcinoma. Epidemiology. 2013;24:671–81.PubMedCrossRef Long XD, Zhao D, Wang C, Huang XY, Yao JG, Ma Y, et al. Genetic polymorphisms in DNA repair genes XRCC4 and XRCC5 and aflatoxin b1-related hepatocellular carcinoma. Epidemiology. 2013;24:671–81.PubMedCrossRef
2.
go back to reference Song P. Standardizing management of hepatocellular carcinoma in china: devising evidence-based clinical practice guidelines. Biosci Trends. 2013;7:250–2.PubMed Song P. Standardizing management of hepatocellular carcinoma in china: devising evidence-based clinical practice guidelines. Biosci Trends. 2013;7:250–2.PubMed
3.
go back to reference Zheng J, Li C, Wu X, Yang Y, Hao M, Sheng S, et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial-mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumour Biol. 2014;35:2265–9.PubMedCrossRef Zheng J, Li C, Wu X, Yang Y, Hao M, Sheng S, et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial-mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumour Biol. 2014;35:2265–9.PubMedCrossRef
4.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
5.
go back to reference Nahon P, Zucman-Rossi J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J Hepatol. 2012;57:663–74.PubMedCrossRef Nahon P, Zucman-Rossi J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J Hepatol. 2012;57:663–74.PubMedCrossRef
6.
go back to reference Lin CH, Lin CC, Tsai CW, Chang WS, Yang CW, Bau DT. Association of caveolin-1 genotypes with gastric cancer in Taiwan. Anticancer Res. 2014;34:2263–7.PubMed Lin CH, Lin CC, Tsai CW, Chang WS, Yang CW, Bau DT. Association of caveolin-1 genotypes with gastric cancer in Taiwan. Anticancer Res. 2014;34:2263–7.PubMed
7.
go back to reference Senetta R, Stella G, Pozzi E, Sturli N, Massi D, Cassoni P. Caveolin-1 as a promoter of tumour spreading: when, how, where and why. J Cell Mol Med. 2013;17:325–36.PubMedCrossRef Senetta R, Stella G, Pozzi E, Sturli N, Massi D, Cassoni P. Caveolin-1 as a promoter of tumour spreading: when, how, where and why. J Cell Mol Med. 2013;17:325–36.PubMedCrossRef
8.
go back to reference Wiechen K, Diatchenko L, Agoulnik A, Scharff KM, Schober H, Arlt K, et al. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. Am J Pathol. 2001;159:1635–43.PubMedCentralPubMedCrossRef Wiechen K, Diatchenko L, Agoulnik A, Scharff KM, Schober H, Arlt K, et al. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. Am J Pathol. 2001;159:1635–43.PubMedCentralPubMedCrossRef
9.
go back to reference Sugie S, Tsukino H, Yamauchi T, Mukai S, Fujii M, Shibata N, et al. Functional polymorphism in the cav1 T29107A gene and its association with prostate cancer risk among Japanese men. Anticancer Res. 2013;33:1023–7.PubMed Sugie S, Tsukino H, Yamauchi T, Mukai S, Fujii M, Shibata N, et al. Functional polymorphism in the cav1 T29107A gene and its association with prostate cancer risk among Japanese men. Anticancer Res. 2013;33:1023–7.PubMed
10.
go back to reference Trimmer C, Bonuccelli G, Katiyar S, Sotgia F, Pestell RG, Lisanti MP, et al. Cav1 suppresses tumor growth and metastasis in a murine model of cutaneous SCC through modulation of MAPK/AP-1 activation. Am J Pathol. 2013;182:992–1004.PubMedCentralPubMedCrossRef Trimmer C, Bonuccelli G, Katiyar S, Sotgia F, Pestell RG, Lisanti MP, et al. Cav1 suppresses tumor growth and metastasis in a murine model of cutaneous SCC through modulation of MAPK/AP-1 activation. Am J Pathol. 2013;182:992–1004.PubMedCentralPubMedCrossRef
11.
go back to reference Vizkeleti L, Ecsedi S, Rakosy Z, Begany A, Emri G, Toth R, et al. Prognostic relevance of the expressions of CAV1 and TES genes on 7q31 in melanoma. Front Biosci (Elite Ed). 2012;4:1802–12.CrossRef Vizkeleti L, Ecsedi S, Rakosy Z, Begany A, Emri G, Toth R, et al. Prognostic relevance of the expressions of CAV1 and TES genes on 7q31 in melanoma. Front Biosci (Elite Ed). 2012;4:1802–12.CrossRef
12.
go back to reference Hsu CM, Yang MD, Tsai CW, Ho CY, Chang WS, Chang SC, et al. The contribution of caveolin-1 genotype and phenotype to hepatocellular carcinoma. Anticancer Res. 2013;33:671–7.PubMed Hsu CM, Yang MD, Tsai CW, Ho CY, Chang WS, Chang SC, et al. The contribution of caveolin-1 genotype and phenotype to hepatocellular carcinoma. Anticancer Res. 2013;33:671–7.PubMed
13.
go back to reference Engelman JA, Zhang XL, Lisanti MP. Genes encoding human caveolin-1 and −2 are co-localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers. FEBS Lett. 1998;436:403–10.PubMedCrossRef Engelman JA, Zhang XL, Lisanti MP. Genes encoding human caveolin-1 and −2 are co-localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers. FEBS Lett. 1998;436:403–10.PubMedCrossRef
14.
go back to reference Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG. Caveolin, a protein component of caveolae membrane coats. Cell. 1992;68:673–82.PubMedCrossRef Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG. Caveolin, a protein component of caveolae membrane coats. Cell. 1992;68:673–82.PubMedCrossRef
15.
go back to reference Shin J, Kim J, Ryu B, Chi SG, Park H. Caveolin-1 is associated with VCAM-1 dependent adhesion of gastric cancer cells to endothelial cells. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2006;17:211–20.CrossRef Shin J, Kim J, Ryu B, Chi SG, Park H. Caveolin-1 is associated with VCAM-1 dependent adhesion of gastric cancer cells to endothelial cells. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2006;17:211–20.CrossRef
16.
go back to reference Sloan EK, Stanley KL, Anderson RL. Caveolin-1 inhibits breast cancer growth and metastasis. Oncogene. 2004;23:7893–7.PubMedCrossRef Sloan EK, Stanley KL, Anderson RL. Caveolin-1 inhibits breast cancer growth and metastasis. Oncogene. 2004;23:7893–7.PubMedCrossRef
17.
go back to reference Belanger MM, Gaudreau M, Roussel E, Couet J. Role of caveolin-1 in etoposide resistance development in A549 lung cancer cells. Cancer Biol Ther. 2004;3:954–9.PubMedCrossRef Belanger MM, Gaudreau M, Roussel E, Couet J. Role of caveolin-1 in etoposide resistance development in A549 lung cancer cells. Cancer Biol Ther. 2004;3:954–9.PubMedCrossRef
18.
go back to reference Sunaga N, Miyajima K, Suzuki M, Sato M, White MA, Ramirez RD, et al. Different roles for caveolin-1 in the development of non-small cell lung cancer versus small cell lung cancer. Cancer Res. 2004;64:4277–85.PubMedCrossRef Sunaga N, Miyajima K, Suzuki M, Sato M, White MA, Ramirez RD, et al. Different roles for caveolin-1 in the development of non-small cell lung cancer versus small cell lung cancer. Cancer Res. 2004;64:4277–85.PubMedCrossRef
19.
go back to reference Patlolla JM, Swamy MV, Raju J, Rao CV. Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines. Oncol Rep. 2004;11:957–63.PubMed Patlolla JM, Swamy MV, Raju J, Rao CV. Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines. Oncol Rep. 2004;11:957–63.PubMed
20.
go back to reference Hino M, Doihara H, Kobayashi K, Aoe M, Shimizu N. Caveolin-1 as tumor suppressor gene in breast cancer. Surg Today. 2003;33:486–90.PubMed Hino M, Doihara H, Kobayashi K, Aoe M, Shimizu N. Caveolin-1 as tumor suppressor gene in breast cancer. Surg Today. 2003;33:486–90.PubMed
21.
go back to reference Mouraviev V, Li L, Tahir SA, Yang G, Timme TM, Goltsov A, et al. The role of caveolin-1 in androgen insensitive prostate cancer. J Urol. 2002;168:1589–96.PubMedCrossRef Mouraviev V, Li L, Tahir SA, Yang G, Timme TM, Goltsov A, et al. The role of caveolin-1 in androgen insensitive prostate cancer. J Urol. 2002;168:1589–96.PubMedCrossRef
22.
go back to reference Rajjayabun PH, Garg S, Durkan GC, Charlton R, Robinson MC, Mellon JK. Caveolin-1 expression is associated with high-grade bladder cancer. Urology. 2001;58:811–4.PubMedCrossRef Rajjayabun PH, Garg S, Durkan GC, Charlton R, Robinson MC, Mellon JK. Caveolin-1 expression is associated with high-grade bladder cancer. Urology. 2001;58:811–4.PubMedCrossRef
23.
go back to reference Thompson TC. Metastasis-related genes in prostate cancer: the role of caveolin-1. Cancer Metastasis Rev. 1998;17:439–42.PubMedCrossRef Thompson TC. Metastasis-related genes in prostate cancer: the role of caveolin-1. Cancer Metastasis Rev. 1998;17:439–42.PubMedCrossRef
24.
go back to reference Hayashi K, Matsuda S, Machida K, Yamamoto T, Fukuda Y, Nimura Y, et al. Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Res. 2001;61:2361–4.PubMed Hayashi K, Matsuda S, Machida K, Yamamoto T, Fukuda Y, Nimura Y, et al. Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Res. 2001;61:2361–4.PubMed
Metadata
Title
Genetic variations of CAV1 gene contribute to HCC risk: a case–control study
Authors
Xixue Zhao
Guozheng Pan
Qingzhong Yuan
Dongpo Mu
Jun Zhang
Tao Cui
Jian Zhang
Linghai Zhang
Publication date
01-11-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2428-5

Other articles of this Issue 11/2014

Tumor Biology 11/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine