Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: The Fukuoka colorectal cancer study

Tomoko Hagiwara, Suminori Kono, Guang Yin, Kengo Toyomura, Jun Nagano, Tetsuya Mizoue, Ryuichi Mibu, Masao Tanaka, Yoshihiro Kakeji, Yoshihiko Maehara, Takeshi Okamura, Kouji Ikejiri, Kitaroh Futami, Youichi Yasunami, Takafumi Maekawa, Kenji Takenaka, Hitoshi Ichimiya, Nobutoshi Imaizumi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.

Original languageEnglish
Pages (from-to)2979-2982
Number of pages4
JournalCancer Research
Volume65
Issue number7
DOIs
Publication statusPublished - Apr 1 2005

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Genetic Polymorphisms
Cytochrome P-450 Enzyme System
Colorectal Neoplasms
Genotype
Bile Acids and Salts
Colonic Neoplasms
Odds Ratio
Cholesterol
Cholesterol 7-alpha-Hydroxylase
Confidence Intervals
Enzymes
Rectal Neoplasms
Restriction Fragment Length Polymorphisms
Japan
Carcinogenesis
Polymerase Chain Reaction
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer : The Fukuoka colorectal cancer study. / Hagiwara, Tomoko; Kono, Suminori; Yin, Guang; Toyomura, Kengo; Nagano, Jun; Mizoue, Tetsuya; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Kouji; Futami, Kitaroh; Yasunami, Youichi; Maekawa, Takafumi; Takenaka, Kenji; Ichimiya, Hitoshi; Imaizumi, Nobutoshi.

In: Cancer Research, Vol. 65, No. 7, 01.04.2005, p. 2979-2982.

Research output: Contribution to journalArticle

Hagiwara, T, Kono, S, Yin, G, Toyomura, K, Nagano, J, Mizoue, T, Mibu, R, Tanaka, M, Kakeji, Y, Maehara, Y, Okamura, T, Ikejiri, K, Futami, K, Yasunami, Y, Maekawa, T, Takenaka, K, Ichimiya, H & Imaizumi, N 2005, 'Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: The Fukuoka colorectal cancer study', Cancer Research, vol. 65, no. 7, pp. 2979-2982. https://doi.org/10.1158/0008-5472.CAN-04-3872
Hagiwara, Tomoko ; Kono, Suminori ; Yin, Guang ; Toyomura, Kengo ; Nagano, Jun ; Mizoue, Tetsuya ; Mibu, Ryuichi ; Tanaka, Masao ; Kakeji, Yoshihiro ; Maehara, Yoshihiko ; Okamura, Takeshi ; Ikejiri, Kouji ; Futami, Kitaroh ; Yasunami, Youichi ; Maekawa, Takafumi ; Takenaka, Kenji ; Ichimiya, Hitoshi ; Imaizumi, Nobutoshi. / Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer : The Fukuoka colorectal cancer study. In: Cancer Research. 2005 ; Vol. 65, No. 7. pp. 2979-2982.
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AU - Mizoue, Tetsuya

AU - Mibu, Ryuichi

AU - Tanaka, Masao

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

AU - Okamura, Takeshi

AU - Ikejiri, Kouji

AU - Futami, Kitaroh

AU - Yasunami, Youichi

AU - Maekawa, Takafumi

AU - Takenaka, Kenji

AU - Ichimiya, Hitoshi

AU - Imaizumi, Nobutoshi

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N2 - Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.

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