Abstract 2759: Possible later age of breast cancer onset for Hispanic BRCA1 carriers with the protective rs140068132-G allele
2015
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA
Hispanic women in the U.S. have lower incidence of breast cancer compared to Non-Hispanic Whites (NHW). A genome-wide association study (GWAS) of breast cancer in Hispanics reported a relatively strong protective variant near the ESR1 gene, only observed among women with Indigenous American ancestry (rs140068132-A/G). The study also reported lower mammographic density among women who were homozygous for the Indigenous American variant (G) and a stronger protective effect for estrogen receptor negative (ER-) breast cancer. In the present study, we assessed if this variant had an effect on age at breast cancer diagnosis among Hispanic BRCA1 carriers, who commonly present with ER- disease. We combined data from four studies of Hispanic BRCA1 mutation carriers with breast cancer: the Clinical Cancer Genetics Community Research Network (CCGCRN; N = 152), Northern California Breast Cancer Family Registry (NC-BCFR, N = 27), and two studies in Latin America, one from Colombia (N = 33) and one from Chile (N = 27). We genotyped the rs140068132 variant using a Taqman assay following the recommended protocol. We used a non-parametric Kruskal-Wallis equality-of-populations rank test to evaluate if the age of breast cancer diagnosis was associated with the rs140068132 polymorphism among BRCA1 carriers. We conducted separate analyses of Hispanic women from California and women from Colombia and Chile. For the California studies, we also had information on ovarian cancer status and were able to conduct stratified analyses. Among 239 BRCA1 carriers, we observed 201 homozygous AA, 36 heterozygous AG, and 2 missing genotypes, with an overall allele frequency of the G allele of 7.6%. We did not find a statistically significant effect of rs140068132 on age at diagnosis among Hispanic BRCA1 carriers overall. However, we found a suggestion of later age at diagnosis, with median age at diagnosis of 39.8 years (33-46 years) in AA homozygous compared to 44 years (34-50 years) in heterozygous (p value = 0.1) women from California. Among women without ovarian cancer either before or after the breast cancer diagnosis, the difference in age at breast cancer diagnosis by genotype was slightly stronger (p value 0.06). We did not observe an association among the patients from Colombia and Chile. Studies of BRCA mutation carriers are often limited by selection for breast cancer cases, thus there may be a bias against enrollment of BRCA carriers with the protective allele in the present analysis. The observed suggestion of a difference in age at diagnosis in the samples from California, similar to genome-wide identified variants that have been shown to have an effect among BRCA1 and BRCA2 carriers, warrants further investigation.
Citation Format: Laura Fejerman, Jeffrey N. Weitzel, Esther M. John, Cynthia Villarreal, Gary Unzeitig, Darling Horcasitas, Charite Ricker, Adrian Daneri, Kayla Castaneda, Alexander Miron, Ana Marie Tuazon, Magdalena Echeverry, Pilar Carvallo, Carolina Alvarez, Teresa Tapia, Columbus Consortium, Luis Carvajal-Carmona, Susan Neuhausen, Elad Ziv. Possible later age of breast cancer onset for Hispanic BRCA1 carriers with the protective rs140068132-G allele. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2759. doi:10.1158/1538-7445.AM2015-2759
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