Passarelli, Michael N.
https://orcid.org/0000-0002-6804-2528
Mayo Clinic
Dartmouth–Hitchcock Medical Center
Citations 2
Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer
Rodriguez‐Broadbent, Henry , Law, Philip , Sud, Amit , Palin, Kimmo , Tuupanen, Sari, Gylfe, Alexandra E., Hänninen, Ulrika A. , Cajuso, Tatiana , Tanskanen, Tomas , Kondelin, Johanna , Kaasinen, Eevi , Sarin, Antti‐Pekka , Rissanen, Harri , Knekt, Paul , Jousilahti, Pekka , Palotie, Aarno , Renkonen‐Sinisalo, Laura , Lepistö, Anna , Böhm, Jan , Mecklin, Jukka‐Pekka , Tassan, Nada Al , Palles, Claire , Martin, Lynn , Barclay, Ella, Farrington, Susan M. , Timofeeva, Maria , Wakil, Salma M. , Campbell, Harry , Idziaszczyk, Shelley, Kaplan, Richard , Kerr, Rachel , Kerr, David , Passarelli, Michael N. , Figueiredo, Jane C. , Buchanan, Daniel D. , Win, Aung Ko , Jenkins, Mark A. , Lindor, Noralane M. , Gallinger, Steven , Conti, David V. , Schumacher, Fredrick R. , Casey, Graham , Aaltonen, Lauri A. , Cheadle, Jeremy P. , Tomlinson, Ian , Dunlop, Malcolm G. , Houlston, Richard S. , Law, Philip J , Buchanan, Daniel D , Win, Aung K , Ripatti, Samuli , Eriksson, Johan G. , Pukkala, Eero , Salomaa, Veikko , Palotie, Aarno V. , Meyer, Brian F. , Smith, Christopher G. , Maughan, Tim , Hopper, John L. , Newcomb, Polly A. , Houlston, Richard S , Jenkins, Mark A , Kaplan, Richard , Kerr, Rachel , Palles, Claire , Conti, David V
International Journal of Cancer | March 25, 2017 | Volume: 140 | Issue: 12 | Pages: 2701-2708
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10−4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.
A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences
Hoffmann, Thomas J. , Jorgenson, Eric , Habel, Laurel A. , Passarelli, Michael N. , Cario, Clinton L. , Emami, Nima C. , Chao, Chun , Ghai, Nirupa R. , Shan, Jun , Ranatunga, Dilrini K., Aaronson, David S., Presti, Joseph C. , Berndt, Sonja I. , McDonnell, Shannon K. , French, Amy J. , Schaid, Daniel J. , Thibodeau, Stephen N. , Freedman, Matthew L. , Mucci, Lorelei A. , Haiman, Christopher A. , Henderson, Brian E., Seminara, Daniela, Kvale, Mark , Schaefer, Catherine , Risch, Neil , Witte, John S. , Wang, Zhaoming , Van Den Eeden, Stephen K , Sakoda, Lori C. , Graff, Rebecca E. , Quesenberry, Charles P. , Wang, Zhaoming , Chanock, Stephen Jacob , Li, Qiyuan , Penney, Kathryn , Kwok, Pui–Yan , Wang, Zhaoming , McDonnell, Shannon K
Cancer Discovery | June 2, 2015 | Volume: 5 | Issue: 8 | Pages: 878-891
Abstract A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 × 10−19 (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 × 10−23) and SLC22A3 (P = 3.2 × 10−52). At the known 19q13.33 locus, rs2659124 (P = 1.3 × 10−13; OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P < 1.0 × 10−8). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P = 0.004). Significance: Taken together, our findings of independent risk variants, ethnic variation in existing SNP replication, and remaining unexplained heritability have important implications for further clarifying the genetic risk of prostate cancer. Our findings also suggest that there may be much promise in evaluating understudied variation, such as indels and ethnically diverse populations. Cancer Discov; 5(8); 878–91. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 783