Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer

the InterLymph Consortium

doi:10.1093/ije/dyab042

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer

the InterLymph Consortium

School of Public Health

Research output: Contribution to journal › Article › peer-review

Abstract

Background: 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. Methods: 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). Results: Higher CLL-PRS was associated with increased BCC risk (OR_{4th-quartile-vs-1stquartile} ¼ 1.13, 95% CI: 1.02-1.24, P_trend ¼ 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (P_trend ¼ 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 (OR_{4th-quartile-vs-1st-quartile} ¼ 1.22, 95% CI: 1.08-1.38, P_trend ¼ 1.36 × 10^-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion: 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.

Original language	English
Pages (from-to)	1325-1334
Number of pages	10
Journal	International Journal of Epidemiology
Volume	50
Issue number	4
DOIs	https://doi.org/10.1093/ije/dyab042
State	Published - 30 Aug 2021

Bibliographical note

Publisher Copyright:
© 2021 Oxford University Press. All rights reserved.

Keywords

CLL
NMSC
Pleiotropy
Polygenic risk score

ASJC Scopus subject areas

Epidemiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/ije/dyab042

Cite this

@article{dc83cad668b540d9bff705a2a22b3519,

title = "Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer",

abstract = "Background: 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. Methods: 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). Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1stquartile ¼ 1.13, 95% CI: 1.02-1.24, Ptrend ¼ 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend ¼ 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 ¼ 1.22, 95% CI: 1.08-1.38, Ptrend ¼ 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion: 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.",

keywords = "CLL, NMSC, Pleiotropy, Polygenic risk score",

author = "{the InterLymph Consortium} and Caroline Besson and Amy Moore and Wenting Wu and Vajdic, {Claire M.} and {de Sanjose}, Silvia and Camp, {Nicola J.} and Smedby, {Karin E.} and Shanafelt, {Tait D.} and Morton, {Lindsay M.} and Brewer, {Jerry D.} and Lydia Zablotska and Li, {Shengchao A.} and Chung, {Charles C.} and Teras, {Lauren R.} and Geffen Kleinstern and Alain Monnereau and Eleanor Kane and Yolanda Benavente and Purdue, {Mark P.} and Birmann, {Brenda M.} and Link, {Brian K.} and Vermeulen, {Roel C.H.} and Spinelli, {John J.} and Demetrius Albanes and Arslan, {Alan A.} and Lucia Miligi and Molina, {Thierry J.} and Skibola, {Christine F.} and Yawei Zhang and Wendy Cozen and Anthony Staines and Caporaso, {Neil E.} and Giles, {Graham G.} and Southey, {Melissa C.} and Milne, {Roger L.} and Tinker, {Lesley F.} and Severson, {Richard K.} and Mads Melbye and Adami, {Hans Olov} and Bengt Glimelius and Bracci, {Paige M.} and Lucia Conde and Martha Glenn and Karen Curtin and Qing Lan and Tongzhang Zheng and Stephanie Weinstein and Brooks-Wilson, {Angela R.} and Diver, {W. Ryan} and Jacqueline Clavel",

year = "2021",

month = aug,

day = "30",

doi = "10.1093/ije/dyab042",

language = "English",

volume = "50",

pages = "1325--1334",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer

AU - the InterLymph Consortium

AU - Besson, Caroline

AU - Moore, Amy

AU - Wu, Wenting

AU - Vajdic, Claire M.

AU - de Sanjose, Silvia

AU - Camp, Nicola J.

AU - Smedby, Karin E.

AU - Shanafelt, Tait D.

AU - Morton, Lindsay M.

AU - Brewer, Jerry D.

AU - Zablotska, Lydia

AU - Li, Shengchao A.

AU - Chung, Charles C.

AU - Teras, Lauren R.

AU - Kleinstern, Geffen

AU - Monnereau, Alain

AU - Kane, Eleanor

AU - Benavente, Yolanda

AU - Purdue, Mark P.

AU - Birmann, Brenda M.

AU - Link, Brian K.

AU - Vermeulen, Roel C.H.

AU - Spinelli, John J.

AU - Albanes, Demetrius

AU - Arslan, Alan A.

AU - Miligi, Lucia

AU - Molina, Thierry J.

AU - Skibola, Christine F.

AU - Zhang, Yawei

AU - Cozen, Wendy

AU - Staines, Anthony

AU - Caporaso, Neil E.

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Milne, Roger L.

AU - Tinker, Lesley F.

AU - Severson, Richard K.

AU - Melbye, Mads

AU - Adami, Hans Olov

AU - Glimelius, Bengt

AU - Bracci, Paige M.

AU - Conde, Lucia

AU - Glenn, Martha

AU - Curtin, Karen

AU - Lan, Qing

AU - Zheng, Tongzhang

AU - Weinstein, Stephanie

AU - Brooks-Wilson, Angela R.

AU - Diver, W. Ryan

AU - Clavel, Jacqueline

PY - 2021/8/30

Y1 - 2021/8/30

N2 - Background: 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. Methods: 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). Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1stquartile ¼ 1.13, 95% CI: 1.02-1.24, Ptrend ¼ 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend ¼ 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 ¼ 1.22, 95% CI: 1.08-1.38, Ptrend ¼ 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion: 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.

AB - Background: 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. Methods: 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). Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1stquartile ¼ 1.13, 95% CI: 1.02-1.24, Ptrend ¼ 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend ¼ 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 ¼ 1.22, 95% CI: 1.08-1.38, Ptrend ¼ 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion: 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.

KW - CLL

KW - NMSC

KW - Pleiotropy

KW - Polygenic risk score

UR - http://www.scopus.com/inward/record.url?scp=85115938241&partnerID=8YFLogxK

U2 - 10.1093/ije/dyab042

DO - 10.1093/ije/dyab042

M3 - Article

C2 - 33748835

AN - SCOPUS:85115938241

SN - 0300-5771

VL - 50

SP - 1325

EP - 1334

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 4

ER -

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this