Abstract
Purpose
Common germline variation in the 5′ region proximal to precursor (pre-) miRNA gene sequences is evaluated for association with breast cancer risk and survival among African Americans and Caucasians.
Methods
We genotyped nine single nucleotide polymorphisms (SNPs) within six miRNA gene regions previously associated with breast cancer, in 1,972 cases and 1,776 controls. In a race-stratified analysis using unconditional logistic regression, odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to evaluate SNP association with breast cancer risk. Additionally, hazard ratios (HRs) for breast cancer-specific mortality were estimated.
Results
Two miR-185 SNPs provided suggestive evidence of an inverse association with breast cancer risk (rs2008591, OR = 0.72 (95 % CI = 0.53–0.98, p value = 0.04) and rs887205, OR = 0.71 (95 % CI = 0.52–0.96, p value = 0.03), respectively) among African Americans. Two SNPs, miR-34b/34c (rs4938723, HR = 0.57 (95 % CI = 0.37–0.89, p value = 0.01)) and miR-206 (rs6920648, HR = 0.77 (95 % CI = 0.61–0.97, p value = 0.02)), provided evidence of association with breast cancer survival. Further adjustment for stage resulted in more modest associations with survival (HR = 0.65 [95 % CI = 0.42–1.02, p value = 0.06] and HR = 0.79 [95 % CI = 0.62–1.00, p value = 0.05, respectively]).
Conclusions
Our results suggest that germline variation in the 5′ region proximal to pre-miRNA gene sequences may be associated with breast cancer risk among African Americans and breast cancer-specific survival generally; however, further validation is needed to confirm these findings.
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Abbreviations
- 3′-UTR:
-
3′-Untranslated region
- AIMs:
-
Ancestry informative markers
- CBCS:
-
Carolina Breast Cancer Study
- cDNA:
-
Complementary DNA made from an mRNA template
- CI:
-
Confidence interval
- CIS:
-
Breast carcinoma in situ
- HR:
-
Hazard ratio
- kb:
-
Kilobase
- LD:
-
Linkage disequilibrium
- MAF:
-
Minor allele frequency
- miRNA or miR:
-
MicroRNA
- mRNA:
-
Messenger RNA
- nt:
-
Nucleotide
- OR:
-
Odds ratio
- Pol II:
-
Polymerase II
- Pol III:
-
Polymerase III
- pre-miRNA:
-
Precursor microRNA
- pri-miRNA:
-
Primary miRNA transcript
- SNP:
-
Single nucleotide polymorphism
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Acknowledgments
The authors would like to acknowledge the UNC BioSpecimen Processing Facility for our DNA extractions, blood processing, storage, and sample disbursement (https://genome.unc.edu/bsp) and the UNC Mammalian Genotyping Core for CBCS sample genotyping (http://mgc.unc.edu). The authors would also like to thank Amy Otto for her thorough review and editing. This work was supported by the Specialized Program of Research Excellence (SPORE) in Breast Cancer at UNC funded by National Institute of Health/National Cancer Institute [P50-CA58223] (supports JTB, CKT, and RCM); the Lineberger Comprehensive Cancer Center Core Grant funded by the National Institute of Health/National Cancer Institute [P30-CA16086] (funded manuscript preparation and submission), and by the Lineberger Comprehensive Cancer Center Cancer Control Education Program Predoctoral Fellowship [R25 CA57726] (supported SJN).
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The authors declare that they have no conflict of interest.
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All experiments comply with the current laws of the United States of America, where they were performed.
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Dr. Robert C. Millikan—deceased.
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Bensen, J.T., Tse, C.K., Nyante, S.J. et al. Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study. Cancer Causes Control 24, 1099–1109 (2013). https://doi.org/10.1007/s10552-013-0187-z
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DOI: https://doi.org/10.1007/s10552-013-0187-z