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Estrogen receptor‐β gene polymorphism and colorectal cancer risk: Effect modified by body mass index and isoflavone intake |
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| Authors: | Naoko Honma Ken Yamamoto Keizo Ohnaka Makiko Morita Kengo Toyomura Suminori Kono Masaaki Muramatsu Tomio Arai Takashi Ueki Masao Tanaka Yoshihiro Kakeji Yoshihiko Maehara Takeshi Okamura Koji Ikejiri Kitaroh Futami Takafumi Maekawa Yohichi Yasunami Kenji Takenaka Hitoshi Ichimiya Reiji Terasaka |
| Affiliation: | 1. Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanTel.: +81‐3‐3964‐3241 (Ext 3047), Fax: +81‐3‐3579‐4776;2. Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan;3. Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;4. Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;5. Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan;6. Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan;7. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;8. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;9. Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan;10. Division of Surgery, National Kyushu Medical Center, Fukuoka, Japan;11. Department of Surgery, Fukuoka University Chikushi Hospital, Chikushino‐shi, Japan;12. Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan;13. Division of Surgery, Fukuoka City Hospital, Fukuoka, Japan;14. Division of Surgery, Hamanomachi General Hospital, Fukuoka, Japan;15. Division of Surgery, Fukuoka Red Cross Hospital, Fukuoka, Japan |
| Abstract: | Estrogen receptor (ER)‐β signaling has generally been implicated in protection against colorectal cancer. The ER‐β gene cytosine‐adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community‐based case‐control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein‐labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age‐adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m?2) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism. |
| Keywords: | estrogen receptor‐β CA repeat polymorphism colorectal cancer body mass index isoflavone age |