GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12

Chizu Tanikawa, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Karine Leveque, Satoshi Nagayama, Koshi Mimori, Masaki Mori, Hideshi Ishii, Johji Inazawa, Jun Yasuda, Akito Tsuboi, Atsushi Shimizu, Makoto Sasaki, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Mariko Naito, Kenji WakaiTeruhide Koyama, Toshiro Takezaki, Koichiro Yuji, Yoshinori Murakami, Yusuke Nakamura, Michiaki Kubo, Koichi Matsuda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC loci. However, most of the previous studies were conducted in European population, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6692 cases and 27 178 controls followed by a replication analysis using more than 11 000 case-control samples. We found the significant association of 10 loci (P < 5 × 10-8), including 2 novel loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 × 10-9 and odds ratio = 1.107 with 95% confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668, P = 4.47 × 10-11 and odds ratio = 0.897 with 95% CI of 0.868-0.926). Moreover, 35 previously reported single nucleotide polymorphisms (SNPs) in 24 regions were validated in the Japanese population (P < 0.05) with the same risk allele as in the previous studies. SNP rs6065668 was significantly associated with TOX2 expression in the sigmoid colon. In addition, nucleotide substitutions in the regulatory region of TOX2 were predicted to alter the binding of several transcription factors, including KLF5. Our findings elucidate the important role of genetic variations in the development of CRC in the Japanese population.

Original languageEnglish
Pages (from-to)652-660
Number of pages9
JournalCarcinogenesis
Volume39
Issue number5
DOIs
Publication statusPublished - 03-05-2018

Fingerprint

Genome-Wide Association Study
Colorectal Neoplasms
Population
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Nucleic Acid Regulatory Sequences
Population Genetics
Sigmoid Colon
Transcription Factors
Nucleotides
Alleles
Mortality
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Tanikawa, C., Kamatani, Y., Takahashi, A., Momozawa, Y., Leveque, K., Nagayama, S., ... Matsuda, K. (2018). GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12. Carcinogenesis, 39(5), 652-660. https://doi.org/10.1093/carcin/bgy026
Tanikawa, Chizu ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Momozawa, Yukihide ; Leveque, Karine ; Nagayama, Satoshi ; Mimori, Koshi ; Mori, Masaki ; Ishii, Hideshi ; Inazawa, Johji ; Yasuda, Jun ; Tsuboi, Akito ; Shimizu, Atsushi ; Sasaki, Makoto ; Yamaji, Taiki ; Sawada, Norie ; Iwasaki, Motoki ; Tsugane, Shoichiro ; Naito, Mariko ; Wakai, Kenji ; Koyama, Teruhide ; Takezaki, Toshiro ; Yuji, Koichiro ; Murakami, Yoshinori ; Nakamura, Yusuke ; Kubo, Michiaki ; Matsuda, Koichi. / GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12. In: Carcinogenesis. 2018 ; Vol. 39, No. 5. pp. 652-660.
@article{edc4899fb715449e8a0767f01fc8e721,
title = "GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12",
abstract = "Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC loci. However, most of the previous studies were conducted in European population, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6692 cases and 27 178 controls followed by a replication analysis using more than 11 000 case-control samples. We found the significant association of 10 loci (P < 5 × 10-8), including 2 novel loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 × 10-9 and odds ratio = 1.107 with 95{\%} confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668, P = 4.47 × 10-11 and odds ratio = 0.897 with 95{\%} CI of 0.868-0.926). Moreover, 35 previously reported single nucleotide polymorphisms (SNPs) in 24 regions were validated in the Japanese population (P < 0.05) with the same risk allele as in the previous studies. SNP rs6065668 was significantly associated with TOX2 expression in the sigmoid colon. In addition, nucleotide substitutions in the regulatory region of TOX2 were predicted to alter the binding of several transcription factors, including KLF5. Our findings elucidate the important role of genetic variations in the development of CRC in the Japanese population.",
author = "Chizu Tanikawa and Yoichiro Kamatani and Atsushi Takahashi and Yukihide Momozawa and Karine Leveque and Satoshi Nagayama and Koshi Mimori and Masaki Mori and Hideshi Ishii and Johji Inazawa and Jun Yasuda and Akito Tsuboi and Atsushi Shimizu and Makoto Sasaki and Taiki Yamaji and Norie Sawada and Motoki Iwasaki and Shoichiro Tsugane and Mariko Naito and Kenji Wakai and Teruhide Koyama and Toshiro Takezaki and Koichiro Yuji and Yoshinori Murakami and Yusuke Nakamura and Michiaki Kubo and Koichi Matsuda",
year = "2018",
month = "5",
day = "3",
doi = "10.1093/carcin/bgy026",
language = "English",
volume = "39",
pages = "652--660",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "5",

}

Tanikawa, C, Kamatani, Y, Takahashi, A, Momozawa, Y, Leveque, K, Nagayama, S, Mimori, K, Mori, M, Ishii, H, Inazawa, J, Yasuda, J, Tsuboi, A, Shimizu, A, Sasaki, M, Yamaji, T, Sawada, N, Iwasaki, M, Tsugane, S, Naito, M, Wakai, K, Koyama, T, Takezaki, T, Yuji, K, Murakami, Y, Nakamura, Y, Kubo, M & Matsuda, K 2018, 'GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12', Carcinogenesis, vol. 39, no. 5, pp. 652-660. https://doi.org/10.1093/carcin/bgy026

GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12. / Tanikawa, Chizu; Kamatani, Yoichiro; Takahashi, Atsushi; Momozawa, Yukihide; Leveque, Karine; Nagayama, Satoshi; Mimori, Koshi; Mori, Masaki; Ishii, Hideshi; Inazawa, Johji; Yasuda, Jun; Tsuboi, Akito; Shimizu, Atsushi; Sasaki, Makoto; Yamaji, Taiki; Sawada, Norie; Iwasaki, Motoki; Tsugane, Shoichiro; Naito, Mariko; Wakai, Kenji; Koyama, Teruhide; Takezaki, Toshiro; Yuji, Koichiro; Murakami, Yoshinori; Nakamura, Yusuke; Kubo, Michiaki; Matsuda, Koichi.

In: Carcinogenesis, Vol. 39, No. 5, 03.05.2018, p. 652-660.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12

AU - Tanikawa, Chizu

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Momozawa, Yukihide

AU - Leveque, Karine

AU - Nagayama, Satoshi

AU - Mimori, Koshi

AU - Mori, Masaki

AU - Ishii, Hideshi

AU - Inazawa, Johji

AU - Yasuda, Jun

AU - Tsuboi, Akito

AU - Shimizu, Atsushi

AU - Sasaki, Makoto

AU - Yamaji, Taiki

AU - Sawada, Norie

AU - Iwasaki, Motoki

AU - Tsugane, Shoichiro

AU - Naito, Mariko

AU - Wakai, Kenji

AU - Koyama, Teruhide

AU - Takezaki, Toshiro

AU - Yuji, Koichiro

AU - Murakami, Yoshinori

AU - Nakamura, Yusuke

AU - Kubo, Michiaki

AU - Matsuda, Koichi

PY - 2018/5/3

Y1 - 2018/5/3

N2 - Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC loci. However, most of the previous studies were conducted in European population, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6692 cases and 27 178 controls followed by a replication analysis using more than 11 000 case-control samples. We found the significant association of 10 loci (P < 5 × 10-8), including 2 novel loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 × 10-9 and odds ratio = 1.107 with 95% confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668, P = 4.47 × 10-11 and odds ratio = 0.897 with 95% CI of 0.868-0.926). Moreover, 35 previously reported single nucleotide polymorphisms (SNPs) in 24 regions were validated in the Japanese population (P < 0.05) with the same risk allele as in the previous studies. SNP rs6065668 was significantly associated with TOX2 expression in the sigmoid colon. In addition, nucleotide substitutions in the regulatory region of TOX2 were predicted to alter the binding of several transcription factors, including KLF5. Our findings elucidate the important role of genetic variations in the development of CRC in the Japanese population.

AB - Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC loci. However, most of the previous studies were conducted in European population, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6692 cases and 27 178 controls followed by a replication analysis using more than 11 000 case-control samples. We found the significant association of 10 loci (P < 5 × 10-8), including 2 novel loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 × 10-9 and odds ratio = 1.107 with 95% confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668, P = 4.47 × 10-11 and odds ratio = 0.897 with 95% CI of 0.868-0.926). Moreover, 35 previously reported single nucleotide polymorphisms (SNPs) in 24 regions were validated in the Japanese population (P < 0.05) with the same risk allele as in the previous studies. SNP rs6065668 was significantly associated with TOX2 expression in the sigmoid colon. In addition, nucleotide substitutions in the regulatory region of TOX2 were predicted to alter the binding of several transcription factors, including KLF5. Our findings elucidate the important role of genetic variations in the development of CRC in the Japanese population.

UR - http://www.scopus.com/inward/record.url?scp=85057768490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057768490&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgy026

DO - 10.1093/carcin/bgy026

M3 - Article

C2 - 29471430

AN - SCOPUS:85057768490

VL - 39

SP - 652

EP - 660

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 5

ER -

Tanikawa C, Kamatani Y, Takahashi A, Momozawa Y, Leveque K, Nagayama S et al. GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12. Carcinogenesis. 2018 May 3;39(5):652-660. https://doi.org/10.1093/carcin/bgy026