Fig 1.
The HMMR locus and breast cancer risk in BRCA1 mutation carriers.
(A) Forest plots showing rs299290 HRs and 95% CIs (retrospective likelihood trend estimation) for participating countries (relatively small sample sets are not shown) ordered by sample size. Left and right panels show results for BRCA1 and BRCA2 mutation carriers, respectively. The sizes of the rectangles are proportional to the corresponding country/study precision. (B) The rs299290-containing region, including the genes, variation and regulatory evidence mentioned in HMECs. Exons are marked by black-filled rectangles and the direction of transcription is marked by arrows in the genomic structure. The chromosome 5 positions (base pairs (bp)) and linkage disequilibrium structure from Caucasian HapMap individuals are also shown.
Fig 2.
Candidate amino acid sites under positive selection in RHAMM and BRCA1.
(A) Plot showing the position of potentially selected sites (p (w > 1)) in the amino acid sequence of RHAMM. The relative position of known protein domains is shown. (B) Plot showing the position of potentially selected sites (p (w > 1)) in the amino acid sequence of BRCA1. The relative position of known protein domains is shown.
Fig 3.
The AURKA/CSTF1 locus and breast cancer risk in BRCA2 mutation carriers.
(A) Forest plots showing rs2426618 HRs and 95% CIs (retrospective likelihood trend estimation) for participating countries (relatively small sample sets are not shown) ordered by sample size. Left and right panels show results for BRCA1 and BRCA2 mutation carriers, respectively. The sizes of the rectangles are proportional to the corresponding study precision. (B) The rs2426618-containing region, including the genes, variation and regulatory evidence in HMECs. Exons are marked by black-filled rectangles and the direction of transcription is marked by arrows in the genomic structure. The chromosome 20 positions (bp) and linkage disequilibrium structure from Caucasian HapMap individuals are also shown.
Table 1.
Potential GxG associated with breast cancer risk in BRCA1/2 mutation carriers.
Fig 4.
Gene expression interactions in breast cancer survival.
(A) Kaplan–Meier survival curves based on categorization of HMMR (probe NM_012484) and AURKA (NM_003600) expression in tertiles (low, medium or high expression). For simplicity, only the tertiles for “high” AURKA are shown. The tumours with high expression levels for both genes were not those with the poorest prognosis. (B) Kaplan–Meier survival curves based on categorization of HMMR (NM_012484) and TUBG1 (NM_016437) expression in tertiles (low, medium or high expression). For simplicity, only the tertiles for “high” HMMR are shown. The cases with high expression levels for both genes were those with the poorest prognosis.