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Quantifying the Genetic Correlation between Multiple Cancer Types

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Quantifying the Genetic Correlation between Multiple Cancer Types. / Lindström, Sara; Finucane, Hilary K; Bulik-Sullivan, Brendan; Schumacher, Fredrick R; Amos, Christopher I; Hung, Rayjean J; Rand, Kristin; Gruber, Stephen B; Conti, David; Permuth, Jennifer B; Lin, Hui-Yi; Goode, Ellen L; Sellers, Thomas A; Amundadottir, Laufey T; Stolzenberg-Solomon, Rachael Z; Klein, Alison P; Petersen, Gloria M; Risch, Harvey A; Wolpin, Brian M; Hsu, Li; Huyghe, Jeroen R; Chang-Claude, Jenny; Chan, Andrew; Berndt, Sonja I; Eeles, Rosalind; Easton, Douglas; Haiman, Christopher A; Hunter, David J; Neale, Benjamin M; Price, Alkes L; Kraft, Peter; PanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO.

In: CANCER EPIDEM BIOMAR, Vol. 26, No. 9, 09.2017, p. 1427-1435.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lindström, S, Finucane, HK, Bulik-Sullivan, B, Schumacher, FR, Amos, CI, Hung, RJ, Rand, K, Gruber, SB, Conti, D, Permuth, JB, Lin, H-Y, Goode, EL, Sellers, TA, Amundadottir, LT, Stolzenberg-Solomon, RZ, Klein, AP, Petersen, GM, Risch, HA, Wolpin, BM, Hsu, L, Huyghe, JR, Chang-Claude, J, Chan, A, Berndt, SI, Eeles, R, Easton, D, Haiman, CA, Hunter, DJ, Neale, BM, Price, AL, Kraft, P & PanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO 2017, 'Quantifying the Genetic Correlation between Multiple Cancer Types', CANCER EPIDEM BIOMAR, vol. 26, no. 9, pp. 1427-1435. https://doi.org/10.1158/1055-9965.EPI-17-0211

APA

Lindström, S., Finucane, H. K., Bulik-Sullivan, B., Schumacher, F. R., Amos, C. I., Hung, R. J., Rand, K., Gruber, S. B., Conti, D., Permuth, J. B., Lin, H-Y., Goode, E. L., Sellers, T. A., Amundadottir, L. T., Stolzenberg-Solomon, R. Z., Klein, A. P., Petersen, G. M., Risch, H. A., Wolpin, B. M., ... PanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO (2017). Quantifying the Genetic Correlation between Multiple Cancer Types. CANCER EPIDEM BIOMAR, 26(9), 1427-1435. https://doi.org/10.1158/1055-9965.EPI-17-0211

Vancouver

Lindström S, Finucane HK, Bulik-Sullivan B, Schumacher FR, Amos CI, Hung RJ et al. Quantifying the Genetic Correlation between Multiple Cancer Types. CANCER EPIDEM BIOMAR. 2017 Sep;26(9):1427-1435. https://doi.org/10.1158/1055-9965.EPI-17-0211

Bibtex

@article{1e54cfa570db45319290e4232b8476a7,
title = "Quantifying the Genetic Correlation between Multiple Cancer Types",
abstract = "Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10(-6)). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427-35. {\textcopyright}2017 AACR.",
keywords = "Journal Article",
author = "Sara Lindstr{\"o}m and Finucane, {Hilary K} and Brendan Bulik-Sullivan and Schumacher, {Fredrick R} and Amos, {Christopher I} and Hung, {Rayjean J} and Kristin Rand and Gruber, {Stephen B} and David Conti and Permuth, {Jennifer B} and Hui-Yi Lin and Goode, {Ellen L} and Sellers, {Thomas A} and Amundadottir, {Laufey T} and Stolzenberg-Solomon, {Rachael Z} and Klein, {Alison P} and Petersen, {Gloria M} and Risch, {Harvey A} and Wolpin, {Brian M} and Li Hsu and Huyghe, {Jeroen R} and Jenny Chang-Claude and Andrew Chan and Berndt, {Sonja I} and Rosalind Eeles and Douglas Easton and Haiman, {Christopher A} and Hunter, {David J} and Neale, {Benjamin M} and Price, {Alkes L} and Peter Kraft and {PanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO}",
note = "{\textcopyright}2017 American Association for Cancer Research.",
year = "2017",
month = sep,
doi = "10.1158/1055-9965.EPI-17-0211",
language = "English",
volume = "26",
pages = "1427--1435",
journal = "CANCER EPIDEM BIOMAR",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

RIS

TY - JOUR

T1 - Quantifying the Genetic Correlation between Multiple Cancer Types

AU - Lindström, Sara

AU - Finucane, Hilary K

AU - Bulik-Sullivan, Brendan

AU - Schumacher, Fredrick R

AU - Amos, Christopher I

AU - Hung, Rayjean J

AU - Rand, Kristin

AU - Gruber, Stephen B

AU - Conti, David

AU - Permuth, Jennifer B

AU - Lin, Hui-Yi

AU - Goode, Ellen L

AU - Sellers, Thomas A

AU - Amundadottir, Laufey T

AU - Stolzenberg-Solomon, Rachael Z

AU - Klein, Alison P

AU - Petersen, Gloria M

AU - Risch, Harvey A

AU - Wolpin, Brian M

AU - Hsu, Li

AU - Huyghe, Jeroen R

AU - Chang-Claude, Jenny

AU - Chan, Andrew

AU - Berndt, Sonja I

AU - Eeles, Rosalind

AU - Easton, Douglas

AU - Haiman, Christopher A

AU - Hunter, David J

AU - Neale, Benjamin M

AU - Price, Alkes L

AU - Kraft, Peter

AU - PanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO

N1 - ©2017 American Association for Cancer Research.

PY - 2017/9

Y1 - 2017/9

N2 - Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10(-6)). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427-35. ©2017 AACR.

AB - Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10(-6)). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427-35. ©2017 AACR.

KW - Journal Article

U2 - 10.1158/1055-9965.EPI-17-0211

DO - 10.1158/1055-9965.EPI-17-0211

M3 - SCORING: Journal article

C2 - 28637796

VL - 26

SP - 1427

EP - 1435

JO - CANCER EPIDEM BIOMAR

JF - CANCER EPIDEM BIOMAR

SN - 1055-9965

IS - 9

ER -