Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism

Wang, Lizhong; Habuchi, Tomonori; Mitsumori, Kenji; Li, Zhenhua; Kamoto, Toshiyuki; Kinoshita, Hidefumi; Tsuchiya, Norihiko; Sato, Kazunari; Οhyama, Chikara; Nakamura, Akira; Ogawa, Osamu; Kato, Takumi

doi:10.1002/ijc.10793

Cited by 81 publications

(53 citation statements)

References 27 publications

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“…The A870 polymorphism of cyclin D1 is associated with increased PCa risk (26,27). However, the prevalence of this genotype in established PCa models and association with cyclin D1b production had yet to be assessed.…”

Section: G͞a870 Polymorphism and Cyclin D1bmentioning

confidence: 99%

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Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation

Burd¹,

Petre²,

Morey³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

131

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Cyclin D1 is a multifaceted regulator of both transcription and cell-cycle progression that exists in two distinct isoforms, cyclin D1a and D1b. In the prostate, cyclin D1a acts through discrete mechanisms to negatively regulate androgen receptor (AR) activity and thus limit androgen-dependent proliferation. Accordingly, cyclin D1a is rarely overexpressed in prostatic adenocarcinoma and holds little prognostic value in this tumor type. However, a common polymorphism (A870) known to facilitate production of cyclin D1b is associated with increased prostate cancer risk. Here we show that cyclin D1b is expressed at high frequency in prostate cancer and is up-regulated in neoplastic disease. Furthermore, our data demonstrate that, although cyclin D1b retains AR association, it is selectively compromised for AR regulation. The altered ability of cyclin D1b to regulate the AR was observed by using both in vitro and in vivo assays and was associated with compromised regulation of AR-dependent proliferation. Consistent with previous reports, expression of cyclin D1a inhibited cell-cycle progression in AR-dependent prostate cancer cells. Strikingly, cyclin D1b significantly stimulated proliferation in this cell type. AR-negative prostate cancer cells were nonresponsive to cyclin D1 (a or b) expression, indicating that defects in AR corepressor function yield a growth advantage specifically in AR-dependent cells. In summary, these studies indicate that the altered AR regulatory capacity of cyclin D1b contributes to its association with increased prostate cancer risk and provide evidence of cyclin D1b-mediated transcriptional regulation.corepressor ͉ G870A ͉ polymorphism ͉ cell cycle ͉ thyroid hormone receptor ␤

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Section: G͞a870 Polymorphism and Cyclin D1bmentioning

confidence: 99%

“…A polymorphism (G͞A870) of the cyclin D1 locus has recently been associated with increased cancer risk for a wide variety of tumors, including PCa (25)(26)(27). Individuals harboring the A870 allele demonstrate an increased propensity to produce an alternatively spliced cyclin D1 mRNA (transcript b).…”

mentioning

confidence: 99%

Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation

Burd¹,

Petre²,

Morey³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

131

View full text Add to dashboard Cite

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“…Several studies have identified a correlation between the CCND1 870A allele and an increased cancer risk, including bladder , prostate ,liver and breast cancer (Wang et al, 2002;Wang et al, 2003;Akkiz et al, 2010;Canbay et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Specific CCND1 G870A Alleles Associated with Breast Cancer Susceptibility: a Meta-analysis of 5,528 Cases and 5,353 Controls

Cui

Shen²,

Wang³

2012

Asian Pacific Journal of Cancer Prevention

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Background: The Cyclin D1(CCND1) G870A polymorphism may be associated with breast cancer, but the evidence from individual studies is inconclusive. The aim of this study was to investigate the correlation between the CCND1 G870A polymorphism and breast cancer risk in a meta-analysis. Materials and Methods: We searched Pubmed and analysed 11 articles on 5,528 cases and 5,353 controls before February 1, 2012. Results: we found there are significant association for AA versus GG and AA versus GA/GG. No significant associations were found for GA versus GG, GA/AA versus GG. There are significant association for AA versus GG ,and AA versus GA/GG in Caucasians. We didn't find any significant main effects for G870A polymorphism on breast cancer risk either in recessive or dominant models in Asians. Conclusion: This meta-analysis suggests that AA of the CCND1 G870A polymorphism is associated with breast cancer susceptibility.

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“…Previous studies have had inconsistent results for an association of the CCND1 A870G polymorphism with bladder cancer (Cortessis et al, 2003;Wang et al, 2003b;Berman et al, 2004;Ito et al, 2004), endometrial cancer (Kang et al, 2005), breast cancer (Grieu et al, 2003;Krippl et al, 2003;Shu et al, 2005), head and neck cancer (Zheng et al, 2001), gastric and oesophageal cancer (Wang et al, 2003c;Zhang et al, 2003a), hepatocellular carcinoma (Zhang et al, 2003b), lung cancer (Qiuling et al, 2003), and prostate cancer (Koike et al, 2003;Wang et al, 2003a). The strongest evidence, to date, has linked the CCND1 A870G polymorphism with an increased risk of colorectal cancer and adenoma in many (Kong et al, 2000(Kong et al, , 2001Bala and Peltomaki, 2001;Porter et al, 2002) though not all studies (McKay et al, 2000).…”

mentioning

confidence: 99%

Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma

et al. 2006

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Cyclin D1 (CCND1) plays a key role in cell cycle control, particularly in the transition from G 1 to S phase, which is regulated by cyclindependent kinases. A common adenine to guanine polymorphism (A870G) in the CCND1 gene has been associated with a longer-life protein and an increased risk of colorectal cancer and adenoma in some studies. Among subjects with hereditary nonpolyposis colorectal cancer, the A870G polymorphism has also been associated with a younger age of onset of colorectal cancer. We analysed 181 colorectal cancer cases and 475 matched controls and 524 adenoma cases and 517 matched controls within women in the Nurses' Health Study (NHS) cohort, 171 colorectal cancer cases and 347 matched controls and 372 adenoma cases and 712 matched controls nested within men in the Health Professionals' Follow-Up Study (HPFS) cohort, and 258 colorectal cancer cases and 415 matched controls within men in the Physicians' Health Study (PHS) cohort to assess the risk associated with the CCND1 A870G genotype. Moreover, we assessed whether CCND1 genotype modified the effect of a sporadic (nonsyndromic) family history of colorectal cancer as well as the effect of other dietary and lifestyle risk factors for colorectal cancer and adenoma. In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82 -1.32) or adenoma (OR, 0.96; 95% CI, 0.79 -1.18). The CCND1 A870G genotype was associated with a modest, although nonsignificantly elevated risk of colorectal cancer (OR, 1.59; 95% CI, 0.98 -2.57) in women. In contrast, the polymorphism was not associated with increased risk of adenoma in either men or women. Among participants with the A870G genotype, a family history of colorectal cancer conferred a substantially greater risk of colorectal cancer in the women (P for interaction ¼ 0.06) and adenoma in the men (P for interaction ¼ 0.02). Current postmenopausal hormone (PMH) use was associated with a significant reduction in the risk of colorectal cancer and adenoma among women with the A870G genotype, whereas there was no effect of PMH use among those with the GG genotype. The CCND1 polymorphism appeared to confer a modest elevation in the risk of colorectal cancer among women. Moreover, the A870G genotype may enhance the protective effect of postmenopausal oestrogen use on the development of colorectal neoplasia.

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Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism

Cited by 81 publications

References 27 publications

Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation

Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation

Specific CCND1 G870A Alleles Associated with Breast Cancer Susceptibility: a Meta-analysis of 5,528 Cases and 5,353 Controls

Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma

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