Journal article
Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer
International journal of epidemiology, Vol.50(4), pp.1325-1334
08/30/2021
DOI: 10.1093/ije/dyab042
PMCID: PMC8521875
PMID: 33748835
Abstract
Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.
We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus.
These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.
Details
- Title: Subtitle
- Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer
- Creators
- Caroline Besson - Centre Hospitalier de VersaillesAmy Moore - National Cancer InstituteWenting Wu - Indiana UniversityClaire M Vajdic - UNSW SydneySilvia de Sanjose - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaNicola J Camp - Huntsman Cancer InstituteKarin E Smedby - Karolinska InstitutetTait D Shanafelt - Department of Internal Medicine, Mayo Clinic, Rochester MN, USA;Lindsay M Morton - National Cancer InstituteJerry D Brewer - Mayo ClinicLydia Zablotska - University of California, San FranciscoEric A Engels - National Cancer InstituteJames R Cerhan - Centre Hospitalier de VersaillesSusan L Slager - Mayo ClinicJiali Han - Brigham and Women's HospitalSonja I Berndt - National Cancer InstituteInterLymph Consortium
- Contributors
- Brian K Link (Contributor) - University of Iowa, Hematology, Oncology, and Blood & Marrow Transplantation
- Resource Type
- Journal article
- Publication Details
- International journal of epidemiology, Vol.50(4), pp.1325-1334
- DOI
- 10.1093/ije/dyab042
- PMID
- 33748835
- PMCID
- PMC8521875
- ISSN
- 0300-5771
- eISSN
- 1464-3685
- Grant note
- P30 CA008748 / NCI NIH HHS
- Language
- English
- Date published
- 08/30/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984359943802771
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