Abstract 2606: Absence of association between common genetic polymorphisms in the TERT-CLPTM1L locus and breast cancer risk in women of African descent

Recent genome wide association studies (GWAS) provided evidence that common low-penetrance single nucleotide polymorphisms (SNPs) contribute to breast cancer development. Common SNPs in the TERT (telomerase reverse transcriptase)-CLPTM1L (cleft lip and palate transmembrane 1 like) locus have been reported to be associated with several types of cancer, such as lung cancer/adenocarcinoma, glioma, bladder cancer, prostate cancer, and pancreatic cancer. Researchers also hypothesized that common SNPs in the TERT gene could play a role in breast cancer susceptibility. However, findings are inconsistent, and most studies included Caucasians only. In the present study, we sought to investigate whether common genetic variants in the TERT-CLPTM1L locus could contribute to breast cancer susceptibility in women of African ancestry. A total 2,892 women of African ancestry were participated in the present study, consisting of 1,509 breast cancer cases and 1,383 controls collected from Nigeria, Barbados, and the United States. Eleven SNPs in the TERT-CLPTM1L locus that were previously shown to be associated with cancers were selected and genotyped using the Illumina GoldenGate Genotyping platform, together with 30 ancestry informative markers (AIMs). Test for HWE suggested that the genotypes for all the SNPs were in Hardy-Weinberg proportions and there was no deviation from HWE. We performed unconditional multiple logistic regression to estimate the association between the TERT-CLPTM1L genetic variants and breast cancer risk, adjusting for age, study site, and estimated genetic ancestry. Overall we did not observe any P value < 0.05 after permutation in the analyses of allelic and genotypic models. We also conducted haplotype analysis for a five-SNP LD block, rs4975616-rs3816659-rs402710-rs401681-rs31489 but again failed to obtain significant association in the present study. Our findings do not support an effect of the tested genetic variants in the TERT-CLPTM1L locus on breast cancer susceptibility in women of African ancestry. However, it is worth noting that our current study did not apply a fine-mapping strategy; other genetic variants in LD with previously reported cancer susceptibility polymorphisms might be bona fide causal variants contributing to the risk of breast cancer. Larger independent studies from diverse populations are expected to evaluate the importance of the TERT-CLPTM1L locus in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]