ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer.
Recently, a nonsense alteration Trp149Stop in the ARLTS1 gene was found more frequently in familial cancer cases versus sporadic cancer patients and healthy controls. Here, the role of Trp149Stop or any other ARLTS1 germline variant was evaluated on breast, prostate, and colorectal cancer risk. The whole gene was screened for germline alterations in 855 familial cancer patients. The five observed variants were further screened in 1169 non-familial cancer patients as well as in 809 healthy population controls. The Trp149Stop was found at low frequencies (0.5-1.2%) in all patient subgroups versus 1.6% in controls, and the mutant allele did not co-segregate with disease status in families with multiple affected individuals. The CC genotype in the Cys148Arg variant was slightly more common among both familial and sporadic breast (odds ratio (OR), 1.48; 95% confidence interval (CI), 1.16-1.87; P=0.001) and prostate cancer patients (OR, 1.50; 95% CI, 1.13-1.99; P=0.005) when compared to controls. A novel ARLTS1 variant Gly65Val was found at higher frequency among familial prostate cancer patients (8 of 164, 4.9%) than in controls (13 of 809, 1.6%; OR, 3.14; 95% CI, 1.28-7.70, P=0.016). However, after adjusting for multiple testing, none of these results were still significant. No association was found with any of the variants and colorectal cancer risk. Our results suggest that Trp149Stop is not a predisposition allele in breast, prostate, or colorectal cancer in the Finnish population, and, while the Gly65Val variant may increase familial prostate cancer risk and the Cys148Arg change may affect both breast and prostate cancer risk, the evidence is not strong in these data.
Siltanen
Sanna
S
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Tampere University Hospital, Tampere, Finland.
Syrjäkoski
Kirsi
K
Fagerholm
Rainer
R
Ikonen
Tarja
T
Lipman
Peter
P
Mallott
Jacob
J
Holli
Kaija
K
Tammela
Teuvo L J
TL
Järvinen
Heikki J
HJ
Mecklin
Jukka-Pekka
JP
Aittomäki
Kristiina
K
Blomqvist
Carl
C
Bailey-Wilson
Joan E
JE
Nevanlinna
Heli
H
Aaltonen
Lauri A
LA
Schleutker
Johanna
J
Vahteristo
Pia
P
D020727:ADP-Ribosylation Factors / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
D020727:ADP-Ribosylation Factors; C500039:ARL11 protein, human