Polymorphisms in Base Excision Repair Genes Are Associated With Endometrial Cancer Risk Among Postmenopausal Japanese Women

Hosono, Satoyo MD, PhD*; Matsuo, Keitaro MD, PhD; Ito, Hidemi MD, PhD*†; Oze, Isao MD, PhD*; Hirose, Kaoru PhD; Watanabe, Miki MSc*; Nakanishi, Toru MD, PhD§; Tajima, Kazuo MD, PhD; Tanaka, Hideo MD, PhD*†

International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0b013e3182a80a7e
Basic Science
Abstract

Objectives: Polymorphisms in base excision repair (BER) genes are associated with risk for several types of cancers but have not been studied with respect to endometrial cancer among Japanese women. Therefore, we conducted a case-control study to explore the association between polymorphisms in BER genes and the risk for endometrial cancer.

Methods/Materials: This study included a total of 91 postmenopausal subjects with endometrial cancer and 261 controls without cancer who visited the Aichi Cancer Center between 2001 and 2005. We focused on single nucleotide polymorphisms within coding regions of 5 BER genes (OGG1, MUTYH, XRCC1, APEX1, and PARP1). To assess lifestyle in the etiology of endometrial cancer, we used a self-administered questionnaire. Associations were evaluated using multivariate unconditional logistic regression models. We also assessed whether there were intergenic associations or an interaction with obesity.

Results: We observed a significant association between endometrial cancer risk and XRCC1 rs1799782 (C > T, Arg194Trp) and XRCC1 rs25487 (G > A, Arg399Gln). We uncovered a significant association between obesity (body mass index, ≥25) and rs25487. The XRCC1 polymorphisms were in complete linkage disequilibrium, and the XRCC1 haplotype TG associated significantly with endometrial cancer risk. The interaction between the CA haplotype and body mass index was marginally significant, whereas interaction between haplotype in XRCC1 and rs1136410 (PARP1) was not significant.

Conclusions: We found a significant association between endometrial cancer risk and XRCC1 polymorphisms and haplotype TG in postmenopausal Japanese women.

Author Information

*Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute; †Department of Epidemiology, Nagoya University Graduate School of Medicine; ‡Department of Planning and Information, Aichi Prefectural Institute of Public Health; §Department of Gynecologic Oncology, Aichi Cancer Center Hospital; ∥Department of Public Health and Occupational Medicine, Mie University Graduate School of Medicine; and ¶Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences.

Address correspondence and reprint requests to Keitaro Matsuo, MD, PhD, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. E-mail: kmatsuo@aichi-cc.jp.

Supported by JSPS KAKENHI grant number 23791866, National Cancer Center Research and Development Fund; a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan; and a Grant-in-Aid for Scientific Research on Priority Areas of Cancer (no. 17015018) and Innovative Areas (no. 221S0001) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

The authors declare no conflicts of interest.

Received May 31, 2013

Accepted August 4, 2013

© 2013 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.