Introduction: Sex-specific differences in observed incidence rates, tumor subsite, and diet and lifestyle associations with colon cancer have been observed. We evaluate sex-specific associations with p53 mutations in colon cancer to add to understanding of these differences. Data from a large population-based incident case-control study of colon cancer were used to evaluate age and gender associations with p53 mutations. To obtain a better understanding of gender-specific associations, we evaluated the role of estrogen as a mediator of risk. For these analyses, women were classified as estrogen positive or negative, based on menopausal status and use of hormone replacement therapy (HRT). Results: There was a significant interaction between age and sex and risk of an acquired p53 mutation compared with p53 Wt. Among men, there was an increase in p53 mutations with age, whereas among women the opposite was observed. Associations with parity, oral contraceptive use, and total ovulatory months were not associated with p53 mutations. However, recent use of HRT reduced risk of all tumors, as did being estrogen positive. Women who were estrogen positive (either premenopausal or recent users of HRT) were at a significantly increased risk of an acquired p53 mutation if they consumed a diet with a high sugar index (odds ratio = 2.94; 95% confidence interval = 1.47-5.89); similar increases in risk of p53 mutations were not observed for menor or women who were estrogen negative. Conclusions: Although sex-specific associations were detected for acquired p53 mutations, they do not indicate a unique role of estrogens in the mutation of p53. These data are consistent with a role for estrogen in altering susceptibility to diet and lifestyle factors possibly via an insulin-related mechanism.
Bibliographical noteFunding Information:
This study was funded by CA48998 and CA61757 to Dr. Slattery. This research was supported by the Utah Cancer Registry, which is funded by Contract N01-PC-67000 from the National Cancer Institute with additional support from the State of Utah Department of Health, the Northern California Cancer Registry, and the Sacramento Tumor Registry. We would like to acknowledge the contributions and support of Margaret Robertson at the University of Utah DNA Sequencing Core Facility, Linda Ballard at the University of Utah Genomics Core Facility, Melanie Nichols and Kristen Gruenthal for laboratory support, and Donna Schaffer, Judy Morse, Sandra Edwards, Leslie Palmer, and Karen Curtin for the data collection and management efforts of this study. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. Address correspondence to M. Slattery, Department of Family and Preventive Medicine, University of Utah Health Research Center, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108. Phone: 801–585–6955. E-mail: firstname.lastname@example.org.