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Association between monoallelic MUTYH mutation and colorectal cancer risk: a meta-regression analysis

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Abstract

Whether people who inherit a mutation in MUTYH from only one parent (monoallelic mutation) are at increased risk of colorectal cancer (CRC) remains controversial. Most previous studies and meta-analyses have not found statistically significant associations but, given carriers are relatively rare, may be underpowered to detect small increased risks. We have conducted a systematic review and meta-regression analysis of previously published case–control studies to estimate the strength of association for monoallelic MUTYH mutation and CRC risk. Potential sources of heterogeneity were evaluated. We have compared the carrier frequency in cases with a family history of CRC to that of controls, as a novel and powerful design, to measure statistical evidence of an association but not the strength of association. The magnitude of the genotype-disease association, estimated from a pooled odds ratio comparing cases unselected for family history with controls, was 1.15 (95% CI = 0.98–1.36) and not substantially altered by adjustment for potential sources of heterogeneity. Monoallelic mutation carrier frequency was greater for cases ascertained due to a family history (3.3%; SE 0.9%) than for controls (1.4%; SE 0.3%) (P = 0.02). Monoallelic MUTYH mutation carriers are at increased risk of CRC but the average increase is small.

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Abbreviations

CRC:

Colorectal cancer

HNPCC:

Hereditary non-polyposis colorectal cancer

MUTYH :

Human MutY homologue

MMR:

Mismatch repair

FAP:

Familial adenomatous polyposis

APC :

Adenomatous polyposis coli

IBD:

Inflammatory bowel disease

CI:

Confidence interval

OR:

Odds ratio

SE:

Standard error

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Acknowledgments

The authors thank corresponding authors of the articles involved in this systematic review and meta-regression analysis for providing required information. This work was partly supported by the National Health and Medical Research Council of Australian Government (Grant No. 628836).

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Correspondence to Mark A. Jenkins.

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Win, A.K., Hopper, J.L. & Jenkins, M.A. Association between monoallelic MUTYH mutation and colorectal cancer risk: a meta-regression analysis. Familial Cancer 10, 1–9 (2011). https://doi.org/10.1007/s10689-010-9399-5

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