Tumor susceptibility and prognosis of breast cancer associated with the G870A polymorphism of CCND1.
We aimed to investigate the role of CCND1 G870A polymorphism genetic and transcriptomic effects susceptibility in association with breast cancer carcinogenesis and clinical prognosis. A case-control study was conducted with the enrollment of 992 sporadic breast cancer patients and the corresponding 960 normal controls from routine mammographic or sonographic screening for breast cancer between 1995 and 2003 in Taiwan. The 167 fragment spanning the G870A polymorphism in exon 4-intron 4 boundary was amplified to identify genotype of CCND1 (G870A) polymorphism. Competitive RT-PCR were further performed to investigate alternative transcript in four different specimens in association with immunohistochemistry markers. The results showed that AG and AA subgroup were at increased risk for developing breast cancer compared with the GG genotype by 19% (OR 1.19 (0.85-1.67)) and by 34% (OR 1.34 (0.04-1.74)), respectively. A870 allele revealed a recessive tendency while GG and AA/AG subgroup was compared (OR 1.35 (1.07-1.70)). AA genotype also had a higher risk in premenopausal women than postmenopausal ones. The recurrence-free survival was longer in patients with GG+AG than that in patients with AA (P = 0.034). A870 allele produced more transcript b both in malignant. There were significant correlations between several immunohistochemistry markers (such as Ki-67) and cyclin D1 or CDk4. We concluded CCND1 G870A polymorphism make significant contribution to breast cancer in the country with the preponderance of breast cancer in young women. The role of G870A polymorphism in alternative transcript was not only implicated in CCND1 alternative splicing but also correlated with immunohistochemistry markers.
Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Cheng-Ping
CP
Yu
Jyh-Cherng
JC
Yu
Chien-An
CA
Sun
Ching
C
Tzao
Jar-Yi
JY
Ho
Amy Ming-Fang
AM
Yen
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics*; D005091:Exons; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007438:Introns; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013624:Taiwan
C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1