Key result
Possessing at least one AGTR1 low-risk genotype combined with the ACE low-activity genotype was associated with a reduced risk of breast cancer (OR 0.35; 95% CI 0.20-0.62).
Why the study?
Do genetic polymorphisms in AGTR1 and ACE genes affect the risk of breast cancer in Chinese women?
Case-Control (n=928)
Do genetic polymorphisms in AGTR1 and ACE genes affect the risk of breast cancer in Chinese women?
Genetic polymorphisms associated with lower AGTR1 and ACE activity are linked to a significantly reduced risk of breast cancer in Chinese women.
Answers are grounded in this paper and cite their sources.
May support lower breast cancer risk with AGTR1/ACE genotypes in Chinese women; hypothesis-generating and requires prospective validation before clinical consideration.
Angiotensin II is converted from its precursor by angiotensin I-converting enzyme (ACE) and has been shown to mediate growth in breast cancer cell lines via ligand-induced activity through the angiotensin II type 1 receptor (AGTR1). Earlier we showed that women with the low activity genotype of the ACE gene have a statistically significantly ( approximately 50%) reduced breast cancer risk compared with those possessing the high activity ACE genotype. To further test the hypothesis that angiotensin II participates in breast carcinogenesis through AGTR1, we examined genetic polymorphisms in the 5'-region of the AGTR1 gene (A-168G, C-535T and T-825A) in relation to risk of breast cancer in 258 breast cancer cases and 670 female controls within the Singapore Chinese Health Study. Relative to the homozygotes, individual genotypes with one or two copies of the respective allelic variants (putative low risk genotypes) were each associated with an approximately 30% reduction in risk of breast cancer. Risk of breast cancer decreased with increasing number of low risk AGTR1 genotypes after adjustment for potential confounders. Relative to those carrying no low risk genotypes (homozygous for A, C and T alleles for the three polymorphisms, respectively), the odds ratios (95% confidence intervals) were 0.84 (0.51-1.37) for women possessing one low risk genotype and 0.68 (0.46-1.01) for women possessing two or three low risk genotypes (P for trend = 0.05). When both AGTR1 and ACE gene polymorphisms were examined simultaneously, women possessing at least one AGTR1 low risk genotype in combination with the ACE low activity genotype had an odds ratio of 0.35 (95% confidence interval, 0.20-0.62) compared with those possessing the ACE high activity genotype and no AGTR1 low risk genotype. Our findings suggest that pharmacological inhibition of the angiotensin II effect by blockade of ACE and/or AGTR1 could be potential targets for the prevention and treatment of breast cancer.
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W.-P. Koh (2004) conducted a case-control in Breast cancer (n=928). AGTR1 low risk genotype and ACE low activity genotype vs. ACE high activity genotype and no AGTR1 low risk genotype was evaluated on Risk of breast cancer (OR 0.35, 95% CI 0.20-0.62). Possessing at least one AGTR1 low-risk genotype combined with the ACE low-activity genotype was associated with a reduced risk of breast cancer (OR 0.35; 95% CI 0.20-0.62).
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