• Park SL, Caberto CP, Lin Y, Goodloe RJ, Dumitrescu L, Love SA, Matise TC, Hindorff LA, Fowke JH, Schumacher FR, Beebe-Dimmer J, Chen C, Hou L, Thomas F, Deelman E, Han Y, Peters U, North KE, Heiss G, Crawford DC, Haiman CA, Wilkens LR, Bush WS, Kooperberg C, Cheng I, Le Marchand L. Association of Cancer Susceptibility Variants with Risk of Multiple Primary Cancers: the Population Architecture using Genomics and Epidemiology Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014 Aug 19. PMID: 25139936 [PubMed].


Background: Multiple primary cancers account for ~16% of all incident cancers in the U.S.. While genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC). Methods: As part of the NHGRI Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort and Women's Health Initiative. Incident MPC (IMPC) cases (n=1,385) were defined as participants diagnosed with >1 incident cancers after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n= 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the association between cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false positive report probability (FPRP) to determine statistical significance. Results: A nicotine dependence-associated and lung cancer variant, CHRNA3 rs578776 (OR=1.16, 95% CI=1.05-1.26; p=0.004) and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR=1.16, 95% CI=1.04-1.28; p=0.005 and OR=1.13, 95% CI=1.03-1.23; p=0.006) were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (p