PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
PBN-AR
Instytucja
Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie
Informacje podstawowe
Główny język publikacji
eng
Czasopismo
Journal of Medical Genetics
ISSN
1468-6244
EISSN
Wydawca
DOI
URL
Rok publikacji
2016
Numer zeszytu
12
Strony od-do
800-811
Numer tomu
53
Identyfikator DOI
Liczba arkuszy
0.55
Słowa kluczowe
en
Cancer: breast, Cancer: ovary, cancer predisposition, Cancer: prostate, Genetics
Streszczenia
Język
en
Treść
BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816TtextgreaterG and c.3113GtextgreaterA, CHEK2 c.349AtextgreaterG, c.538CtextgreaterT, c.715GtextgreaterA, c.1036CtextgreaterT, c.1312GtextgreaterT, and c.1343TtextgreaterG and ATM c.7271TtextgreaterG. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10(-5)), PALB2 c.3113GtextgreaterA OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10(-8)) and ATM c.7271TtextgreaterG OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349AtextgreaterG OR 2.26 (95% CI 1.29 to 3.95), c.1036CtextgreaterT OR 5.06 (95% CI 1.09 to 23.5) and c.538CtextgreaterT OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343TtextgreaterG OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312GtextgreaterT OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Inne
System-identifier
COI760511a21f084bc0884edd5ff914a81f
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