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Open Access 01-03-2020 | Prostate Cancer | Original Paper

Allergy, asthma, and the risk of breast and prostate cancer: a Mendelian randomization study

Authors: Xia Jiang, Niki L. Dimou, Zhaozhong Zhu, Carolina Bonilla, Sarah J. Lewis, Sara Lindström, Peter Kraft, Konstantinos K. Tsilidis, Richard M. Martin, the PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia

Published in: Cancer Causes & Control | Issue 3/2020

Abstract

Purpose

The relationship of allergic diseases, such as asthma, hay fever, and eczema, with cancer is under debate. Observational studies have reported conflicting findings, but such studies are susceptible to confounding and reverse causation. Understanding the potential role of allergy in carcinogenesis may shed new light on the biological mechanisms underpinning intrinsic immunity and cancer.

Methods

We conducted a Mendelian randomization study, using germline genetic variants as instrumental variables, to determine the causal relevance of allergic disease and on two most common malignancies: breast cancer and prostate cancer. We used the summary statistics from the largest ever genome-wide association studies conducted on allergic disease (n_case = 180,129), asthma (n_case = 14,085), breast (n_case = 122,977), and prostate cancer (n_case = 79,148) and calculated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer for allergic disease.

Results

We did not observe any evidence to support a causal association between allergic disease and risk of breast cancer overall [OR 1.00 (95% CI 0.96–1.04), p = 0.95] or by subtype (estrogen receptor (ER)+ [0.99 (0.95–1.04), p = 0.71], ER− [1.05 (0.99–1.10), p = 0.11]). We also did not find any evidence for an association with prostate cancer [1.00 (0.94–1.05), p = 0.93] or advanced subtype [0.97 (0.90–1.05), p = 0.46]. Sensitivity analyses did not reveal directional pleiotropy.

Conclusion

Our study does not support a causal effect of allergic disease on the risk of breast or prostate cancer. Future studies may be conducted to focus on understanding the causal role of allergic disease in cancer prognosis or drug responses (e.g., immunotherapy).

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Johnson KJ (1966) The relation of cancer to allergy. J Lancet 86:5–11PubMed

Shapiro S, Fedullo A (1973) Allergy and cancer. Lancet 301:1055–1056. https://doi.org/10.1016/S0140-6736(73)90686-7 CrossRef

Carrozzi L, Viegi G (2005) Allergy and cancer: a biological and epidemiological rebus. Allergy 60:1095–1097. https://doi.org/10.1111/j.1398-9995.2005.00940.x CrossRefPubMed

Wang H, Diepgen TL (2005) Is atopy a protective or a risk factor for cancer? A review of epidemiological studies. Allergy 60:1098–1111. https://doi.org/10.1111/j.1398-9995.2005.00813.x CrossRefPubMed

Rittmeyer D, Lorentz A (2012) Relationship between allergy and cancer: an overview. Int Arch Allergy Immunol 159:216–225. https://doi.org/10.1159/000338994 CrossRefPubMed

Turner MC, Chen Y, Krewski D, Ghadirian P (2006) An overview of the association between allergy and cancer. Int J Cancer 118:3124–3132. https://doi.org/10.1002/ijc.21752 CrossRefPubMed

Merrill RM, Isakson RT, Beck RE (2007) The association between allergies and cancer: what is currently known? Ann Allergy Asthma Immunol 99:102–116 (quiz 117–119, 150). https://doi.org/10.1016/S1081-1206(10)60632-1 CrossRef

Turner MC (2012) Epidemiology: allergy history, IgE, and cancer. Cancer Immunol Immunother CII 61:1493–1510. https://doi.org/10.1007/s00262-011-1180-6 CrossRefPubMed

Vojtechova P, Martin RM (2009) The association of atopic diseases with breast, prostate, and colorectal cancers: a meta-analysis. Cancer Causes Control CCC 20:1091–1105. https://doi.org/10.1007/s10552-009-9334-y CrossRefPubMed

10.

Zhu J, Song J, Liu Z et al (2016) Association between allergic conditions and risk of prostate cancer: a prisma-compliant systematic review and meta-analysis. Sci Rep 6:35682. https://doi.org/10.1038/srep35682 CrossRefPubMedPubMedCentral

11.

Davey Smith G, Ebrahim S (2003) ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 32:1–22. https://doi.org/10.1093/ije/dyg070 CrossRef

12.

VanderWeele TJ, Tchetgen Tchetgen EJ, Cornelis M, Kraft P (2014) Methodological challenges in mendelian randomization. Epidemiol Camb Mass 25:427–435. https://doi.org/10.1097/EDE.0000000000000081 CrossRef

13.

Ferreira MA, Vonk JM, Baurecht H et al (2017) Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet 49:1752–1757. https://doi.org/10.1038/ng.3985 CrossRefPubMedPubMedCentral

14.

Zhu Z, Lee PH, Chaffin MD et al (2018) A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases. Nat Genet 50:857–864. https://doi.org/10.1038/s41588-018-0121-0 CrossRefPubMedPubMedCentral

15.

Amos CI, Dennis J, Wang Z et al (2016) The ONCOARRAY consortium: a network for understanding the genetic architecture of common cancers. Cancer Epidemiol Biomark Prev Publ. https://doi.org/10.1158/1055-9965.EPI-16-0106 CrossRef

16.

Michailidou K, Lindström S, Dennis J et al (2017) Association analysis identifies 65 new breast cancer risk loci. Nature. https://doi.org/10.1038/nature24284 CrossRefPubMedPubMedCentral

17.

Milne RL, Kuchenbaecker KB, Michailidou K et al (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet. https://doi.org/10.1038/ng.3785 CrossRefPubMedPubMedCentral

18.

Schumacher F, Al Olama A, Berndt S (2018) Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet 50:928–936CrossRef

19.

Burgess S, Scott RA, Timpson NJ et al (2015) Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol 30:543–552. https://doi.org/10.1007/s10654-015-0011-z CrossRefPubMedPubMedCentral

20.

Burgess S, Butterworth A, Thompson SG (2013) Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 37:658–665. https://doi.org/10.1002/gepi.21758 CrossRefPubMedPubMedCentral

21.

Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44:512–525. https://doi.org/10.1093/ije/dyv080 CrossRefPubMedPubMedCentral

22.

Verbanck M, Chen C-Y, Neale B, Do R (2018) Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 50:693–698. https://doi.org/10.1038/s41588-018-0099-7 CrossRefPubMedPubMedCentral

23.

Bowden J, Davey Smith G, Haycock PC, Burgess S (2016) Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40:304–314. https://doi.org/10.1002/gepi.21965 CrossRefPubMedPubMedCentral

24.

Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 32:377–389. https://doi.org/10.1007/s10654-017-0255-x CrossRefPubMedPubMedCentral

25.

Brion M-JA, Shakhbazov K, Visscher PM (2013) Calculating statistical power in Mendelian randomization studies. Int J Epidemiol 42:1497–1501. https://doi.org/10.1093/ije/dyt179 CrossRefPubMed

26.

Severi G, Baglietto L, Muller DC et al (2010) Asthma, asthma medications, and prostate cancer risk. Cancer Epidemiol Biomark Prev Publ 19:2318–2324. https://doi.org/10.1158/1055-9965.EPI-10-0381 CrossRef

27.

Lowcock EC, Cotterchio M, Ahmad N (2013) Association between allergies, asthma, and breast cancer risk among women in Ontario, Canada. Cancer Causes Control CCC 24:1053–1056. https://doi.org/10.1007/s10552-013-0177-1 CrossRefPubMed

28.

Hedderson MM, Malone KE, Daling JR, White E (2003) Allergy and risk of breast cancer among young women (United States). Cancer Causes Control CCC 14:619–626CrossRef

29.

Nakachi K, Hayashi T, Imai K, Kusunoki Y (2004) Perspectives on cancer immuno-epidemiology. Cancer Sci 95:921–929CrossRef

30.

Olson SH, Hsu M, Satagopan JM et al (2013) Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. Am J Epidemiol 178:691–700. https://doi.org/10.1093/aje/kwt052 CrossRefPubMedPubMedCentral

31.

Linos E, Raine T, Alonso A, Michaud D (2007) Atopy and risk of brain tumors: a meta-analysis. J Natl Cancer Inst 99:1544–1550. https://doi.org/10.1093/jnci/djm170 CrossRefPubMed

32.

Vajdic CM, Falster MO, de Sanjose S et al (2009) Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis. Cancer Res 69:6482–6489. https://doi.org/10.1158/0008-5472.CAN-08-4372 CrossRefPubMedPubMedCentral

33.

Santillan AA, Camargo CA, Colditz GA (2003) A meta-analysis of asthma and risk of lung cancer (United States). Cancer Causes Control CCC 14:327–334CrossRef

34.

Turner MC, Chen Y, Krewski D et al (2005) Cancer mortality among US men and women with asthma and hay fever. Am J Epidemiol 162:212–221. https://doi.org/10.1093/aje/kwi193 CrossRefPubMed

35.

Olson SH, Chou JF, Ludwig E et al (2010) Allergies, obesity, other risk factors and survival from pancreatic cancer. Int J Cancer 127:2412–2419. https://doi.org/10.1002/ijc.25240 CrossRefPubMed

36.

Knopf PM (2000) Immunomodulation and allergy. Allergy Asthma Proc 21:215–220CrossRef

37.

Burgess S, Labrecque JA (2018) Mendelian randomization with a binary exposure variable: interpretation and presentation of causal estimates. Eur J Epidemiol 33:947–952. https://doi.org/10.1007/s10654-018-0424-6 CrossRefPubMedPubMedCentral

Title: Allergy, asthma, and the risk of breast and prostate cancer: a Mendelian randomization study
Authors: Xia Jiang
Niki L. Dimou
Zhaozhong Zhu
Carolina Bonilla
Sarah J. Lewis
Sara Lindström
Peter Kraft
Konstantinos K. Tsilidis
Richard M. Martin
the PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia
Publication date: 01-03-2020
Publisher: Springer International Publishing
Keywords: Prostate Cancer
Allergic Rhinitis
Breast Cancer
Bronchial Asthma
Prostate Cancer
Breast Cancer
Published in: Cancer Causes & Control / Issue 3/2020
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-020-01271-7

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Abstract

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