Filaggrin loss-of-function mutations and incident cancer: a population-based study

T Skaaby; L L N Husemoen; J P Thyssen; M Meldgaard; B H Thuesen; C Pisinger; T Jørgensen; K Carlsen; J D Johansen; T Menné; P B Szecsi; S Stender; A Linneberg

doi:10.1111/bjd.12969

Filaggrin loss-of-function mutations and incident cancer: a population-based study

T Skaaby, L L N Husemoen, J P Thyssen, M Meldgaard, B H Thuesen, C Pisinger, T Jørgensen, K Carlsen, J D Johansen, T Menné, P B Szecsi, S Stender, A Linneberg

20 Citationer (Scopus)

Abstract

Background Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. Objectives To investigate the association of the FLG genotype and cancer types in four population-based cohorts. Methods A total of 13 376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. Results There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. Conclusions The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses. What's already known about this topic? Loss-of-function mutations in the filaggrin gene (FLG) affect 8-10% of Northern Europeans and result in ichthyosis vulgaris and high risk of atopic dermatitis. The impaired skin barrier in FLG mutation carriers is associated with 10% higher serum vitamin D levels. What does this study add? Apart from a borderline-significant lower risk of nonmelanoma skin cancer among filaggrin mutation carriers, the filaggrin genotype was not associated with cancer incidence except in subgroup analyses.

Originalsprog	Engelsk
Tidsskrift	British Journal of Dermatology
Vol/bind	171
Udgave nummer	6
Sider (fra-til)	1407-1414
Antal sider	8
ISSN	0007-0963
DOI	https://doi.org/10.1111/bjd.12969
Status	Udgivet - 1 dec. 2014

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10.1111/bjd.12969

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Skaaby, T., Husemoen, L. L. N., Thyssen, J. P., Meldgaard, M., Thuesen, B. H., Pisinger, C., Jørgensen, T., Carlsen, K., Johansen, J. D., Menné, T., Szecsi, P. B., Stender, S., & Linneberg, A. (2014). Filaggrin loss-of-function mutations and incident cancer: a population-based study. British Journal of Dermatology, 171(6), 1407-1414. https://doi.org/10.1111/bjd.12969

@article{137e646cedf24d749c5c4a0ce0f02961,

title = "Filaggrin loss-of-function mutations and incident cancer: a population-based study",

abstract = "Background Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. Objectives To investigate the association of the FLG genotype and cancer types in four population-based cohorts. Methods A total of 13 376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. Results There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. Conclusions The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses. What's already known about this topic? Loss-of-function mutations in the filaggrin gene (FLG) affect 8-10% of Northern Europeans and result in ichthyosis vulgaris and high risk of atopic dermatitis. The impaired skin barrier in FLG mutation carriers is associated with 10% higher serum vitamin D levels. What does this study add? Apart from a borderline-significant lower risk of nonmelanoma skin cancer among filaggrin mutation carriers, the filaggrin genotype was not associated with cancer incidence except in subgroup analyses.",

author = "T Skaaby and Husemoen, {L L N} and Thyssen, {J P} and M Meldgaard and Thuesen, {B H} and C Pisinger and T J{\o}rgensen and K Carlsen and Johansen, {J D} and T Menn{\'e} and Szecsi, {P B} and S Stender and A Linneberg",

note = "{\textcopyright} 2014 British Association of Dermatologists.",

year = "2014",

month = dec,

day = "1",

doi = "10.1111/bjd.12969",

language = "English",

volume = "171",

pages = "1407--1414",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Filaggrin loss-of-function mutations and incident cancer

T2 - a population-based study

AU - Skaaby, T

AU - Husemoen, L L N

AU - Thyssen, J P

AU - Meldgaard, M

AU - Thuesen, B H

AU - Pisinger, C

AU - Jørgensen, T

AU - Carlsen, K

AU - Johansen, J D

AU - Menné, T

AU - Szecsi, P B

AU - Stender, S

AU - Linneberg, A

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Background Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. Objectives To investigate the association of the FLG genotype and cancer types in four population-based cohorts. Methods A total of 13 376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. Results There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. Conclusions The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses. What's already known about this topic? Loss-of-function mutations in the filaggrin gene (FLG) affect 8-10% of Northern Europeans and result in ichthyosis vulgaris and high risk of atopic dermatitis. The impaired skin barrier in FLG mutation carriers is associated with 10% higher serum vitamin D levels. What does this study add? Apart from a borderline-significant lower risk of nonmelanoma skin cancer among filaggrin mutation carriers, the filaggrin genotype was not associated with cancer incidence except in subgroup analyses.

AB - Background Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. Objectives To investigate the association of the FLG genotype and cancer types in four population-based cohorts. Methods A total of 13 376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. Results There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. Conclusions The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses. What's already known about this topic? Loss-of-function mutations in the filaggrin gene (FLG) affect 8-10% of Northern Europeans and result in ichthyosis vulgaris and high risk of atopic dermatitis. The impaired skin barrier in FLG mutation carriers is associated with 10% higher serum vitamin D levels. What does this study add? Apart from a borderline-significant lower risk of nonmelanoma skin cancer among filaggrin mutation carriers, the filaggrin genotype was not associated with cancer incidence except in subgroup analyses.

U2 - 10.1111/bjd.12969

DO - 10.1111/bjd.12969

M3 - Journal article

C2 - 24628370

SN - 0007-0963

VL - 171

SP - 1407

EP - 1414

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 6

ER -

Filaggrin loss-of-function mutations and incident cancer: a population-based study

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