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Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.


ABSTRACT: OBJECTIVE:Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. DESIGN:We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations. RESULTS:Two correlated SNPs--rs10090154 and rs4242382--in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. CONCLUSIONS:This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

SUBMITTER: Cheng I 

PROVIDER: S-EPMC3918490 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.

Cheng Iona I   Kocarnik Jonathan M JM   Dumitrescu Logan L   Lindor Noralane M NM   Chang-Claude Jenny J   Avery Christy L CL   Caberto Christian P CP   Love Shelly-Ann SA   Slattery Martha L ML   Chan Andrew T AT   Baron John A JA   Hindorff Lucia A LA   Park Sungshim Lani SL   Schumacher Fredrick R FR   Hoffmeister Michael M   Kraft Peter P   Butler Anne M AM   Duggan David J DJ   Hou Lifang L   Carlson Chris S CS   Monroe Kristine R KR   Lin Yi Y   Carty Cara L CL   Mann Sue S   Ma Jing J   Giovannucci Edward L EL   Fuchs Charles S CS   Newcomb Polly A PA   Jenkins Mark A MA   Hopper John L JL   Haile Robert W RW   Conti David V DV   Campbell Peter T PT   Potter John D JD   Caan Bette J BJ   Schoen Robert E RE   Hayes Richard B RB   Chanock Stephen J SJ   Berndt Sonja I SI   Küry Sebastien S   Bézieau Stephane S   Ambite Jose Luis JL   Kumaraguruparan Gowri G   Richardson Danielle M DM   Goodloe Robert J RJ   Dilks Holli H HH   Baker Paxton P   Zanke Brent W BW   Lemire Mathieu M   Gallinger Steven S   Hsu Li L   Jiao Shuo S   Harrison Tabitha A TA   Seminara Daniela D   Haiman Christopher A CA   Kooperberg Charles C   Wilkens Lynne R LR   Hutter Carolyn M CM   White Emily E   Crawford Dana C DC   Heiss Gerardo G   Hudson Thomas J TJ   Brenner Hermann H   Bush William S WS   Casey Graham G   Le Marchand Loïc L   Peters Ulrike U  

Gut 20130809 5


<h4>Objective</h4>Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previ  ...[more]

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