Low‐frequency nonsynonymous variants in FKBPL and ARPC1B genes are associated with breast cancer risk in Chinese women

Abstract

Genome-wide association studies have reported more than 100 independent common loci associated with breast cancer risk. The contribution of low-frequency or rare variants to breast cancer susceptibility has not been well explored. Thus, we applied exome chip to genotype >200 000 low-frequency and rare variants in 1064 breast cancer cases and 1125 cancer-free controls and subsequently validated promising associations in another 1040 breast cancer cases and 1240 controls. We identified two low-frequency nonsynonymous variants at FKBPL (rs200847762, OR = 0.34, 95% CI = 0.20-0.57, P = 4.31 × 10 ) and ARPC1B (rs1045012, OR = 0.56, 95% CI = 0.43-0.74, P = 4.30 × 10 ) associated with breast cancer risk. In stratification analyses, we found that the protective effect of rs200847762 was stronger in ER-positive breast cancer (OR = 0.18, 95% CI = 0.06-0.42) than that in ER-negative one (OR = 0.59, 95% CI = 0.31-1.05). Our findings indicate that low-frequency variants may also contribute to breast cancer susceptibility and genetic variants in 6p21.33 and 7q22.1 are important in breast carcinogenesis. © 2016 Wiley Periodicals, Inc.

Quantifying posterior effect size distribution of susceptibility loci by common summary statistics

“…Application of the FAB approach produced the posterior estimate of OR for the discovery study equal to 0.57, with the 95% credible interval (0.33–0.92), suggesting a genuine causal signal within this region (we also report posterior estimates for the median of OR, which are close in values to the estimates of the posterior mean). This signal was further suggested to be in association with breast cancer among Chinese women by Zhou et al (2017). The therapeutic and diagnostic potential of FKBPL to targeting tumors was discussed by Robson and James (2012) and McKeen et al (2011).…”

Quantifying posterior effect size distribution of susceptibility loci by common summary statistics

“…Application of the Mix Bayes approach produced the posterior estimate of OR for the discovery study equal to 0.27, with the 95% Credible Interval (0.133-0.55), suggesting a genuine causal signal within this region (we also report posterior estimates for the median of OR, which are close in values to the estimates of the posterior mean). This signal was further suggested to be in association with breast cancer among Chinese women by Zhou et al 25 The therapeutic and diagnostic potential of FKBPL to targeting tumours was discussed by Robson and James 26 and McKeen et al 27 Genetic variant with the second smallest P-value in Jin et al discovery study was rs2298090 within the HIST1H1E gene (P = 6.16×10 - 5 ). This signal also failed to replicate at the second stage of their study, OR = 0.65, 95% CI (0.44 – 1.02).…”

Effects of potentially functional polymorphisms in suppressor of cytokine signaling 3 (SOCS3) on the risk of head and neck squamous cancer

“…Due to the design failure of probes, rs1887429 was excluded. Finally, a total of seven functional polymorphisms were genotyped in all case and control samples using the Infinium BeadChip platform (Illumina, San Diego, CA), which was described in our previous study . Genotype calling was performed by the GenTrain version 1.0 clustering algorithm in Genome‐Studio V 2011.1 (Illumina, San Diego, CA).…”