Population-based incidence rates and increased risk of <i>EGFR</i> mutated non-small cell lung cancer in Māori and Pacifica in New Zealand

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Abstract

Background

Non-squamous non-small cell lung cancer (NSCLC) patients with Epidermal Growth Factor Receptor ( EGFR) mutation benefit from targeted treatments. Previous studies reported EGFR mutation-positive proportions among tested non-squamous NSCLC patients. However, incidence rates and population risk of EGFR mutation-positive and EGFR mutation-negative non-squamous NSCLC have not been assessed. This study therefore aimed to estimate the population-based incidence rates of EGFR mutation-positive and EGFR mutation-negative non-squamous NSCLC in different population groups defined by sex, ethnic group and smoking status.

Methods

This study included data from all non-squamous NSCLC patients diagnosed in northern New Zealand between 1/02/2010 and 31/07/2017 (N = 3815), obtained from a population-based cancer registry. Age-specific incidence rates, WHO age-standardised rates (ASRs) and rates adjusted for incomplete testing were calculated for EGFR mutation-positive and EGFR mutation-negative diseases for the study cohort as a whole and subgroups of patients.

Results

Among 3815 patients, 45% were tested for EGFR mutations; 22.5% of those tested were EGFR mutation-positive. The ASR of EGFR mutation-positive NSCLC was 5.05 (95%CI 4.71–5.39) per 100,000 person-years. ASRs for EGFR mutation-positive NSCLC were higher for females than males: standardised incidence ratio (SIR) 1.50 (1.31–1.73); higher for Pacifica, Asians and Māori compared with New Zealand Europeans: SIRs 3.47 (2.48–4.85), 3.35 (2.62–4.28), and 2.02 (1.43–2.87), respectively; and, only slightly increased in ever-smokers compared with never-smokers: SIR 1.25 (1.02–1.53). In contrast, the ASR of EGFR mutation-negative NSCLC was 17.39 (16.75–18.02) per 100,000 person-years, showing a strong association with smoking; was higher for men; highest for Māori, followed by Pacifica and then New Zealand Europeans, and lowest for Asians. When corrected for incomplete testing, SIRs by sex, ethnicity and smoking, for both diseases, remained similar to those based on tested patients.

Conclusion

The population risk of EGFR mutation-positive NSCLC was significantly higher for Māori and Pacifica compared with New Zealand Europeans.

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Most cited references 39

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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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Lung cancer: current therapies and new targeted treatments.

Fred Hirsch, Giorgio Scagliotti, James L Mulshine … (2017)

Lung cancer is the most frequent cause of cancer-related deaths worldwide. Every year, 1·8 million people are diagnosed with lung cancer, and 1·6 million people die as a result of the disease. 5-year survival rates vary from 4-17% depending on stage and regional differences. In this Seminar, we discuss existing treatment for patients with lung cancer and the promise of precision medicine, with special emphasis on new targeted therapies. Some subgroups, eg-patients with poor performance status and elderly patients-are not specifically addressed, because these groups require special treatment considerations and no frameworks have been established in terms of new targeted therapies. We discuss prevention and early detection of lung cancer with an emphasis on lung cancer screening. Although we acknowledge the importance of smoking prevention and cessation, this is a large topic beyond the scope of this Seminar.

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Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

Thomas Lynch, Daphne Bell, Raffaella Sordella … (2004)

Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells. Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P<0.001). Mutations were either small, in-frame deletions or amino acid substitutions clustered around the ATP-binding pocket of the tyrosine kinase domain. Similar mutations were detected in tumors from 2 of 25 patients with primary non-small-cell lung cancer who had not been exposed to gefitinib (8 percent). All mutations were heterozygous, and identical mutations were observed in multiple patients, suggesting an additive specific gain of function. In vitro, EGFR mutants demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to inhibition by gefitinib. A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib. Copyright 2004 Massachusetts Medical Society

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Author and article information

Contributors

Phyu Sin Aye:

ORCID: https://orcid.org/0000-0001-9356-9965

Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Mark James McKeage: Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing

Sandar Tin Tin: Role: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – review & editing

Prashannata Khwaounjoo: Role: Data curation

J Mark Elwood: Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing

Rama Krishna Kancha: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS One

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 7 May 2021

Publication date Collection: 2021

Volume: 16

Issue: 5

Electronic Location Identifier: e0251357

Affiliations

[1 ] Epidemiology and Biostatistics, University of Auckland, Auckland, New Zealand

[2 ] Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand

[3 ] Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand

Osmania University, Hyderabad, India, INDIA

Author notes

Competing Interests: The authors have declared that no competing interests exist.

* E-mail: p.aye@ 123456auckland.ac.nz

Author information

Phyu Sin Aye https://orcid.org/0000-0001-9356-9965

Article

Publisher ID: PONE-D-20-40145

DOI: 10.1371/journal.pone.0251357

PMC ID: 8104366

PubMed ID: 33961689

SO-VID: b2a70bda-cb1b-4cff-8ad9-c92f83e3e918

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 21 December 2020

Date accepted : 26 April 2021

Page count

Figures: 2, Tables: 3, Pages: 14

Funding

Funded by: Health Research Council of New Zealand

Award ID: 13-981, 15-087 and 19-450

Award Recipient : Mark James McKeage

Funded by: University of Auckland

Award ID: UoA Doctoral Scholarship

Award Recipient :

ORCID: https://orcid.org/0000-0001-9356-9965

Phyu Sin Aye

This research has been funded by the Health Research Council of New Zealand (funding projects 13-981, 15-087 and 19-450). Phyu Aye’s PhD has been funded by the University of Auckland Doctoral Scholarship. The funders had no role in research design, data collection, data analysis, or preparation of the manuscript for publication.

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Data Availability All of the aggregate data (i.e. counts) required for replicating the calculation of incidence rates and proportions presented in the paper are available within the body of the manuscript or in the Supporting information file. All data-points in the figures are also shown as numerical values in tables or elsewhere. However, individual patient-level data cannot be shared publicly because they contain identifying patient information. Ethical and legal requirements have been imposed upon us, which limit data access and sharing in order to maintain patient confidentiality and privacy, by the New Zealand Government Ministry of Health ethics and governance committees. For ethics queries, please contact Health and Disability Ethics Committees at hdecs@ 123456health.govt.nz .

Population-based incidence rates and increased risk of EGFR mutated non-small cell lung cancer in Māori and Pacifica in New Zealand

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Most cited references 39

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Lung cancer: current therapies and new targeted treatments.

Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

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