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The Health Outcome
Breast cancer is the second most common cancer in the world and the most common cancer in women. It accounts for about 1 in 10 cancers (2). The annual mortality rates range from 27/100,000 women in northern Europe to 4/100,000 in Asia . In the US, there were 192,000 breast cancer cases and 40,000 deaths reported in 2001 (3).
Various genetic polymorphisms have been studied for association with breast cancer. These include genes related to steroid hormone metabolism and carcinogen metabolism (4). Recent studies have suggested a link between high circulating levels of insulin-like factor-I (IGF-I) and an increased risk of breast cancer among premenopausal women (5). Further study showed the association between breast cancer risk and the length of (CA)n repeats in the IGF-I gene (6).
The Finding
Wen et al (1) reported an association of IGFI gene polymorphisms with breast cancer risk and plasma IGF-I level in Chinese women based on a population-based case-control study. The study included 1,041 incident breast cancer cases diagnosed from August 1996 through March 1998 in Shanghai and 1,086 randomly selected age-matched controls from the general population. Although no relation between plasma IGF-I levels and IGFI genotypes was found, the genotypes containing the (CA)17 or (CA)19 allele were associated with a significantly decreased (OR = 0.80, 95% CI: 0.64-1.00) or increased (OR = 1.23, 95% CI: 1.04-1.47) risk of breast cancer, respectively, and the genotypes containing any of the 4 rare alleles, (CA)11, (CA)13, (CA)16 and (CA)23, were associated with a nonsignificantly increased risk of breast cancer (OR = 1.92, 95% CI: 0.92-4.02) compared with those that did not carry the specific alleles. The associations with the (CA)17 or (CA)19 allele were predominantly present among premenopausal women and in a dose-response manner. The meta-analysis results indicated that IGFI genotypes containing the (CA)19 were consistently associated with increased risk of breast cancer across studies (overall OR = 1.22, 95% CI: 1.06-1.41, p for heterogeneity test = 0.524). The findings of this study support the hypothesis that IGFI gene polymorphisms may be a significant genetic factor for breast cancer susceptibility.
Public Health Implications
This study showed a positive association of breast cancer risk with the (CA)19 allele of IGF1; carrier rates of the (CA)19 allele were 62.6% in cases and 58% in controls in this population. The population attributable risk percents (PARP) due to (CA)19 genotype was 9.2% for heterozygous and 11.4% for homozygous IGF1 genotypes in all women. IGF levels were not associated with genotype in this study. However, they were only obtained at one time point, which may not reflect long-term levels. Because blood samples were obtained after cancer diagnosis, the presence of tumor might have affected the level of plasma IGF-I, IGF-II and IGFBP-3. These findings could help us to further understand the relationship between breast cancer and IGF polymorphism in the biology of breast cancer. As a suggestion, simultaneously investigating this gene with another important gene to evaluate gene-gene in teraction could provide better understanding of the gene-disease association. Understanding gene-environment in teractions involving modifiable risk factors could help find relevant intervention strategy for breast cancer.
References
- Wen W, et al. Insulin-like growth factor-I gene polymorphism and breast cancer risk in Chinese women. International Journal of Caner. 2005;113:307-311
- Sasco AJ, et al. Breast cancer and environment, Horm Res. 2003;60(Suppl 3):50
- Lacey JV Jr, et al. Recent trends in breast cancer incidence and mortality. Environ Mol Mutagen. 2002;39:82-88
- Dunning A, et al. A systematic review of genetic polymorpgisms and breast cancer. Cancer Epidemiology, Biomarkers & Prevention. 1999;8:843-854
- Toniolo P, et al. Serum insulin-like growth factor–I and breast cancer. Int J Cancer.
2002;88:828-832
- Yu H, et al. Polymorphic CA repeats in the IGF-I gene and breast cancer. Breast Cancer Res Treat. 2001;70:117-122
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