Wang Lizhong, Habuchi Tomonori, Mitsumori Kenji, Li Zhenhua, Kamoto Toshiyuki, Kinoshita Hidefumi, Tsuchiya Norihiko, Sato Kazunari, Ohyama Chikara, Nakamura Akira, Ogawa Osamu, Kato Tetsuro
Department of Urology, Akita University School of Medicine, Akita, Japan.
Int J Cancer. 2003 Jan 1;103(1):116-20. doi: 10.1002/ijc.10793.
CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1 A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13-3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09-3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65-1.54, BPH: aOR = 0.91, 95% CI 0.60-1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38-6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44-2.34). No significant difference in genotype frequency was found among patients with low-, intermediate- and high-grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1 A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects.
CCND1信使核糖核酸（mRNA）可通过可变剪接产生2种转录本，其剪接模式可能受外显子4保守剪接供体位点内常见的A870G单核苷酸多态性调控。多项研究表明CCND1基因与多种癌症的发生或进展之间存在显著关联。为了研究该多态性与前列腺癌（PCa）遗传易感性及其疾病状态的相关性，我们检测了214例PCa患者、234例良性前列腺增生（BPH）患者和254名男性对照者的该多态性。与对照组相比，在PCa组（p = 0.015）和BPH组（p = 0.018）中，CCND1 A等位基因的出现频率更高。与GG基因型男性相比，AA基因型男性患PCa（优势比[aOR]=1.93，95%可信区间[CI]1.13 - 3.30，p = 0.016）和BPH（aOR = 1.84，95%CI 1.09 - 3.09，p = 0.023）的风险增加。与GG基因型男性相比，AG基因型男性未观察到显著关联（PCa：aOR = 1.00，95%CI 0.65 - 1.54；BPH：aOR = 0.91，95%CI 0.60 - 1.39）。与AA基因型相关的PCa风险在73岁及以下男性中似乎更强（aOR = 2.89，95%CI 1.38 - 6.01，p = 0.005），而在73岁以上男性中未发现关联（aOR = 1.02，95%CI 0.44 - 2.34）。在低级别、中级别和高级别肿瘤患者中（p = 0.730）或局限性和转移性PCa患者之间（p = 0.679），未发现基因型频率有显著差异。然而，在高级别或转移性PCa患者中，与对照组相比，观察到AA基因型相关风险显著增加，而在低/中级别或局限性PCa患者中未发现显著结果。在日本人群中，CCND1 A870G多态性的A等位基因与PCa和BPH易感性呈隐性关联，与GG基因型男性相比，AA基因型男性患PCa和BPH的风险增加2倍。尽管与AA基因型相关的PCa风险似乎尤其在73岁及以下男性中起作用，且A等位基因可能与PCa的疾病状态相关，但这些推测需要在未来更多受试者的研究中得到验证。
