Increased frequency of disease-causing MYH mutations in colon cancer families Journal Article
| Authors: | Peterlongo, P.; Mitra, N.; de Abajo, A. S.; De la Hoya, M.; Bassi, C.; Bertario, L.; Radice, P.; Glogowski, E.; Nafa, K.; Caldés, T.; Offit, K.; Ellis, N. A. |
| Article Title: | Increased frequency of disease-causing MYH mutations in colon cancer families |
| Abstract: | The genetic factors that cause clustering of colorectal cancers (CRCs) other than mutations in the mismatch repair (MMR) genes are not well understood. Clustering in families who lack MMR gene mutations may be attributable to low-penetrance mutations. Hypothetically, mono-allelic MYH mutations could contribute to the risk of CRC in these families. Using Fisher's exact test and logistic regression, we compared the frequency of the known disease-causing MYH mutations Y165C, G382D and 466delE in 137 probands (117 cases with CRC and 20 cases diagnosed on the basis of adenomatous polyps only) from families with three or more CRCs but negative for mutations in the MMR genes and in 967 healthy controls with comparable ethnic backgrounds. Of 137 cases, 6 (4.4%) carried mono-allelic MYH mutations compared with 16 of 967 (1.6%) controls. In addition, three bi-allelic MYH mutation carriers, who eventually developed MYH-associated polyposis, were also identified in families with pedigree structures consistent with dominant inheritance of CRC susceptibility. By Fisher's exact tests, there was a statistically different frequency of cases with any MYH mutation (mono- or bi-allelic carriers; P-value = 0.002) and of cases with mono-allelic MYH mutation (P = 0.04) compared with the controls. Using a logistic regression model, the unadjusted odds ratio associated with any MYH mutation was 4.14 (P-value < 0.001); for mono-allelic carriers, it was 2.79 (P-value = 0.04). Adjusting for ethnic backgrounds, gender and age, the odds ratio associated with any disease-causing MYH mutation was 3.23 (P-value = 0.01); for mono-allelic carriers, it was 1.99 (P-value = 0.20). Overall, the results support previous studies suggesting that mono-allelic mutations of MYH constitute low-penetrance CRC-causing alleles. These data further support a model in which low-penetrance alleles are enriched in MMR gene mutation-negative CRC families. © 2006 Oxford University Press. |
| Keywords: | adult; controlled study; aged; aged, 80 and over; middle aged; unclassified drug; gene mutation; human cell; major clinical study; gene deletion; mutation; case-control studies; cancer risk; allele; cancer susceptibility; heredity; family health; genetic predisposition to disease; cluster analysis; colonic neoplasms; genetic association; age; gene expression regulation, neoplastic; colon cancer; mismatch repair; sex difference; dna mutational analysis; logistic regression analysis; genetic predisposition; ethnic group; fisher exact test; jew; caucasian; colon carcinogenesis; penetrance; hypothesis; pedigree analysis; frequency analysis; nucleic acid binding protein; dna glycosylases; colon polyposis; protein myh; dominant inheritance; family study |
| Journal Title: | Carcinogenesis |
| Volume: | 27 |
| Issue: | 11 |
| ISSN: | 0143-3334 |
| Publisher: | Oxford University Press |
| Date Published: | 2006-11-15 |
| Start Page: | 2243 |
| End Page: | 2249 |
| Language: | English |
| DOI: | 10.1093/carcin/bgl093 |
| PUBMED: | 16774938 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 22" - "Export Date: 4 June 2012" - "CODEN: CRNGD" - "Source: Scopus" |
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243Nafa -
27Glogowski
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