Limits...
Cooperation of DLC1 and CDK6 affects breast cancer clinical outcome.

Dai X, Li L, Liu X, Hu W, Yang Y, Bai Z - G3 (Bethesda) (2014)

Bottom Line: We found that high DLC1 and low CDK6 expression are associated with good prognosis.The DLC1 intronic SNP rs561681 is found to fit a recessive model, complying with the tumor suppressive role of DLC1.The heterozygote of the DLC1 SNP is found to increase the hazard when the CDK6 intronic SNP rs3731343 is rare homozygous, and it becomes protective when rs3731343 is common homozygous.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China School of Biotechnology, Jiangnan University, Wuxi 214122, China Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Show MeSH

Related in: MedlinePlus

Kaplan Meier plots of patients’ survival showing interactions in the identified SNP pair between DLC1 and CDK6. The plots were drawn for the DLC1 SNP (rs561681) stratified by the genotypes of the CDK6 SNP (rs3731343). Results from HEBCS and POSH data were pooled. Plots showing (A–B) the interactive effect of AA:AC/CC (aa:bB/BB, the rare homozygote of the DLC1 SNP vs. the combination of the heterozygote and common homozygote of the CDK6 SNP), (C–D) the interactive effect of AG:AA (aA:bb, the heterozygote of the DLC1 SNP vs. the rare homozygote of the CDK6 SNP), and (E–F) the interactive effect of AG:CC (aA:BB, the heterozygote of the DLC1 SNP vs. the common homozygote of the CDK6 SNP).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4291472&req=5

fig1: Kaplan Meier plots of patients’ survival showing interactions in the identified SNP pair between DLC1 and CDK6. The plots were drawn for the DLC1 SNP (rs561681) stratified by the genotypes of the CDK6 SNP (rs3731343). Results from HEBCS and POSH data were pooled. Plots showing (A–B) the interactive effect of AA:AC/CC (aa:bB/BB, the rare homozygote of the DLC1 SNP vs. the combination of the heterozygote and common homozygote of the CDK6 SNP), (C–D) the interactive effect of AG:AA (aA:bb, the heterozygote of the DLC1 SNP vs. the rare homozygote of the CDK6 SNP), and (E–F) the interactive effect of AG:CC (aA:BB, the heterozygote of the DLC1 SNP vs. the common homozygote of the CDK6 SNP).

Mentions: To explore further the significance of the interactions of various genotype combinations on patient survival, the Kaplan Meier plots of the DLC1 SNP as stratified by the genotypes of the CDK6 SNP were drawn (Figure 1), with the statistics summarized in Table 2. It is shown that the heterozygote of the DLC1 SNP has an amplifying effect on the CDK6 SNP, i.e., it increases the hazard when combined with the rare homozygote of the CDK6 SNP (see Figure 1D and compare it with Figure 1C, Table 2) and becomes protective when interacting with the common homozygote of the CDK6 SNP (see Figure 1E and compare it with Figure 1F, Table 2). Significant protective effect was also observed when fitting both SNPs in the pair to the recessive model, i.e., neither SNP is rare homozygous (see Figure 1A and compare it with Figure 1B, Table 2). As represented by the stratification analysis (Table 2), this effect, although marginally significant in POSH data (P = 0.097, HR = 0.75, 95% C.I.= 0.53, 1.06), has similar patterns in both data sets (Figure S1) and the significance is largely improved in the pooled analysis (P = 0.0035, HR = 0.73, 95% C.I. = 0.59, 0.9). This interaction is significant with and without BRCA patients being removed, indicating its independence of BRCA status. Also, whether the confounding effect of age is adjusted does not make a significant difference here. Importantly, although being less significant than interacting with the nonrare homozygote of the CDK6 SNP, the rare homozygote of the DLC1 SNP significantly increases hazard in HEBCS data and the pooled analysis (Table 2).


Cooperation of DLC1 and CDK6 affects breast cancer clinical outcome.

Dai X, Li L, Liu X, Hu W, Yang Y, Bai Z - G3 (Bethesda) (2014)

Kaplan Meier plots of patients’ survival showing interactions in the identified SNP pair between DLC1 and CDK6. The plots were drawn for the DLC1 SNP (rs561681) stratified by the genotypes of the CDK6 SNP (rs3731343). Results from HEBCS and POSH data were pooled. Plots showing (A–B) the interactive effect of AA:AC/CC (aa:bB/BB, the rare homozygote of the DLC1 SNP vs. the combination of the heterozygote and common homozygote of the CDK6 SNP), (C–D) the interactive effect of AG:AA (aA:bb, the heterozygote of the DLC1 SNP vs. the rare homozygote of the CDK6 SNP), and (E–F) the interactive effect of AG:CC (aA:BB, the heterozygote of the DLC1 SNP vs. the common homozygote of the CDK6 SNP).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4291472&req=5

fig1: Kaplan Meier plots of patients’ survival showing interactions in the identified SNP pair between DLC1 and CDK6. The plots were drawn for the DLC1 SNP (rs561681) stratified by the genotypes of the CDK6 SNP (rs3731343). Results from HEBCS and POSH data were pooled. Plots showing (A–B) the interactive effect of AA:AC/CC (aa:bB/BB, the rare homozygote of the DLC1 SNP vs. the combination of the heterozygote and common homozygote of the CDK6 SNP), (C–D) the interactive effect of AG:AA (aA:bb, the heterozygote of the DLC1 SNP vs. the rare homozygote of the CDK6 SNP), and (E–F) the interactive effect of AG:CC (aA:BB, the heterozygote of the DLC1 SNP vs. the common homozygote of the CDK6 SNP).
Mentions: To explore further the significance of the interactions of various genotype combinations on patient survival, the Kaplan Meier plots of the DLC1 SNP as stratified by the genotypes of the CDK6 SNP were drawn (Figure 1), with the statistics summarized in Table 2. It is shown that the heterozygote of the DLC1 SNP has an amplifying effect on the CDK6 SNP, i.e., it increases the hazard when combined with the rare homozygote of the CDK6 SNP (see Figure 1D and compare it with Figure 1C, Table 2) and becomes protective when interacting with the common homozygote of the CDK6 SNP (see Figure 1E and compare it with Figure 1F, Table 2). Significant protective effect was also observed when fitting both SNPs in the pair to the recessive model, i.e., neither SNP is rare homozygous (see Figure 1A and compare it with Figure 1B, Table 2). As represented by the stratification analysis (Table 2), this effect, although marginally significant in POSH data (P = 0.097, HR = 0.75, 95% C.I.= 0.53, 1.06), has similar patterns in both data sets (Figure S1) and the significance is largely improved in the pooled analysis (P = 0.0035, HR = 0.73, 95% C.I. = 0.59, 0.9). This interaction is significant with and without BRCA patients being removed, indicating its independence of BRCA status. Also, whether the confounding effect of age is adjusted does not make a significant difference here. Importantly, although being less significant than interacting with the nonrare homozygote of the CDK6 SNP, the rare homozygote of the DLC1 SNP significantly increases hazard in HEBCS data and the pooled analysis (Table 2).

Bottom Line: We found that high DLC1 and low CDK6 expression are associated with good prognosis.The DLC1 intronic SNP rs561681 is found to fit a recessive model, complying with the tumor suppressive role of DLC1.The heterozygote of the DLC1 SNP is found to increase the hazard when the CDK6 intronic SNP rs3731343 is rare homozygous, and it becomes protective when rs3731343 is common homozygous.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China School of Biotechnology, Jiangnan University, Wuxi 214122, China Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Show MeSH
Related in: MedlinePlus