Inherited variants in MYH are unlikely to contribute to the risk of lung carcinoma

Abstract

The base excision repair gene MYH protects against damage to DNA from reactive oxygen species, which are commonly found in cigarette smoke. Inherited mutations in MYH predispose to colorectal adenomas and carcinomas that show a characteristic pattern of somatic G:C-->T:A mutations in the APC gene. A similar pattern of somatic mutations in the TP53 gene is reported in smoking-related lung cancers. We therefore tested whether germline changes in MYH may also contribute to the development of lung cancer by screening for variants in 276 patients with lung carcinoma and 106 normal controls. No patients harboured truncating mutations in MYH and only a single patient was a carrier for the G382D missense mutation. We identified three common coding region (V22M, Q324H and S501F) and intronic (157+30A>G, 462+35G>A and 1435-40G>C) variants, but none were over-represented in the patient samples, indicating that MYH variants are unlikely to predispose significantly to the risk of lung cancer.

ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis)

“…Other specific mutations have been reported in the Japanese, Italian, Portuguese, and Finnish populations. 1,[98][99][100] Although a number of mutations in the MUTYH gene have been documented, two missense mutations, p.Y165C and p.G382D, account for 70-80% of mutant alleles in the Northern European population, with a third mutation, 1395delGGA, accounting for ~25% of mutant alleles in persons of a Southern European (Mediterranean) background. 101 The common missense mutations in MUTYH, p.Y165C and p.G382D, have a well-established effect on glycosylase function in experimental systems.…”

Leiden open variation database of the MUTYH gene

“…Tumor types other than colorectal polyps and cancer that have been studied in relation to MUTYH variants include: gastric cancer [Goto et al, 2008;Kim et al, 2004;Tao et al, 2004;Zhang et al, 2006a], prostate cancer [Shin et al, 2007], bladder cancer [Figueroa et al, 2007;Huang et al, 2007], endometrial cancer [Barnetson et al, 2007], lung cancer [Al-Tassan et al, 2004], childhood leukemia [Akyerli et al, 2003], breast cancer [Beiner et al, 2009;Zhang et al, 2006b], hepatocellular carcinoma and cholangiocarcinoma [Baudhuin et al, 2006], and head and neck cancer [Görgens et al, 2007;Sliwinski et al, 2009]. So far, there are no reports of biallelic pathogenic MUTYH variants in the absence of a colorectal phenotype.…”

Analysis of the Oxidative Damage Repair GenesNUDT1,OGG1, andMUTYHin Patients from Mismatch Repair Proficient HNPCC Families (MSS-HNPCC)

“…However, by far, the most striking finding so far has been the identification of biallelic mutations in the MUTYH gene as causing a significant number of attenuated familial adenomatous polyposis (AFAP) cases (19). Regarding the potential role of variants of the BER genes as risk modifiers, some studies have described a possible role in different types of cancer (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). The results concering risk of CRC or adenoma (CRA) have not always coincided (33)(34)(35)(36)(37)(38).…”