Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin

Journal of the National Cancer Institute
Thorunn RafnarKari Stefansson

Abstract

Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old ag...Continue Reading

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May 17, 2018·Journal of the National Cancer Institute·Shailja Pathania, Judy E Garber
Jun 8, 2019·Human Molecular Genetics·Upekha E LiyanageDavid C Whiteman
Feb 20, 2021·Cancer Research·Thorhildur OlafsdottirKari Stefansson

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