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Lack of Association between CCND1 G870A Polymorphism and Risk of Esophageal Squamous Cell Carcinoma¹

Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Introduction

ESCC,³ like most malignant tumors, is primarily a consequent of abnormal cell proliferation induced by uncontrolled cell cycle. Cyclin D1 plays an important role in the transition from G₁ to S phase of the cell cycle and has oncogenic properties. Overexpression of this protein is thought to be related to the development of a variety of tumors, including ESCC (1) . The gene encoding cyclin D1, CCND1, has a common G870A polymorphism at codon 242 in exon 4 that increases the frequency of alternate splicing, leading to an altered protein (2) . The altered cyclin D1 does not contain the sequences involved in protein turnover and, thus, may have a longer acting half-life. It has been suggested that this polymorphism in the CCND1 gene confers susceptibility to certain cancers (3, 4, 5) .

In this study, we analyzed DNA samples from a hospital-based case-control study in a Chinese population to test the hypothesis that the CCND1 G870A polymorphism may be a genetic risk modifier for ESCC.

Materials and Methods

This study included 321 patients with ESCC and 345 age- and gender-matched healthy controls. Patients were consecutively recruited from January 1998 to December 2000 at the Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China). Population controls were accrued from a database of nutritional survey conducted in the same regions. Most of the cases and controls have been characterized in a molecular epidemiological study described elsewhere (6) . The CCND1 G870A genotypes were determined by PCR-restriction fragment length polymorphism method as described previously (4) . The ORs and their 95% CIs calculated by unconditional logistic regression models and adjusted for age, sex, and smoking status were used to estimate risk of ESCC for the CCND1 polymorphism.

Results and Discussion

The allele frequencies for CCND1 870G and 870A were 0.424 and 0.576, respectively, among controls and 0.457 and 0.543, respectively, among cases with ESCC. The distribution of three CCND1 G870A genotypes among cases were not significantly different from that among controls and, thus, the polymorphism did not associated with risk of ESCC (Table 1) . In addition, no evidence for interaction between the polymorphism and tobacco smoking was observed.

Footnotes

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by National Natural Science Foundation Grant 39825122 and from State Key Basic Research Program Grant G1998051204.

² To whom requests for reprints should be addressed, at Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, China. Fax: 86-10-67722460; E-mail: dlin{at}public.bta.net.cn

³ The abbreviations used are: ESCC, esophageal squamous cell carcinoma; OR, odds ratio; CI, confidence interval.

Received 10/11/02; revised 10/11/02; accepted 11/22/02.

References

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2. Betticher D. C., Thatcher N., Altermatt H. J., Hoban P., Ryder D. J., Heighway J. Alternate splicing produces a novel cyclin D1 transcript. Oncogene, 11: 1005-1011, 1995.[Medline]
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4. Zheng Y., Shen H., Erich M. S., Wang L., Susan A. E., Sara S. S., Marsha L. F., Margaret R. S., Wei Q. Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck: a case-control study. Carcinogenesis (Lond.), 22: 1195-1199, 2001.[Abstract/Free Full Text]
5. Wang L., Habuchi T., Takahashi T., Mitsumori K., Kamoto T., Kakehi Y., Kakinuma H., Sato K., Nakamura A., Ogawa O., Kato T. Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer. Carcinogenesis (Lond.), 23: 257-264, 2002.[Abstract/Free Full Text]
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