Genetic polymorphisms in the human growth hormone-1 gene (GH1) and the risk of breast carcinoma.
BACKGROUND
In addition to possessing many physiologic functions, human growth hormone-1 (GH1) has been shown in recent in vitro and in vivo experiments to induce malignant disease, including breast carcinoma. The authors investigated the association of breast carcinoma with genetic polymorphisms in the GH1 gene in the Shanghai Breast Cancer Study.


METHODS
Included in the current investigation were 1193 women with breast carcinoma (case patients) and 1310 healthy women from the same community (control patients) who completed in-person interviews and provided blood samples. Genetic polymorphisms in the proximal promoter region (nucleotide [nt] -162 to nt +148 relative to the transcription start site of the GH1 gene) were searched and confirmed by resequencing DNA samples from 43 study participants. A novel polymorphism, a transition from adenine to guanine at nt 69 (A69G), was identified. Samples from all participants were genotyped with TaqMan 5' nuclease assays for five common single-nucleotide polymorphisms (SNPs)-four in the proximal region (A-75G, G-57T, A-6G, and A69G) and one in intron 4 (T1169A).


RESULTS
The frequencies of occurrence for the minor alleles in these polymorphic sites were 0.04, 0.60, 0.24, 0.03, and 0.34, respectively, in the control group; these frequencies were comparable to those observed in the case group. After adjusting for potential confounding factors, none of the SNPs investigated in this study showed a statistically significant association with breast carcinoma risk. This null association was found for both younger women (age < 45 years) and older women (age > or = 45 years). GH1 gene haplotypes were assessed using SNP data and were analyzed in relation to breast carcinoma risk. Again, none of the haplotypes were associated with breast carcinoma risk.


CONCLUSIONS
The results of the current study suggest that genetic polymorphisms in the proximal promoter region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma risk in Chinese women.
Ren
Zefang
Z
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
Cai
Qiuyin
Q
Shu
Xiao-Ou
XO
Cai
Hui
H
Cheng
Jia-Rong
JR
Wen
Wan-Qing
WQ
Gao
Yu-Tang
YT
Zheng
Wei
W
D044466:Asian People; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D019382:Human Growth Hormone