Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk.
Prolonged estrogen exposure is believed to be the major cause of endometrial cancer. As possible markers of estrogen exposure, various menstrual and reproductive features, e.g., ages at menarche and menopause, are found to be associated with endometrial cancer risk. In order to assess their combined effects on endometrial cancer, we created the total number of menstrual cycles (TNMC) that a woman experienced during her life or up to the time of study and two genetic risk scores, GRS1 for age at menarche and GRS2 for age at menopause. Comparing 482 endometrial cancer patients with 571 population controls, we found TNMC was associated with endometrial cancer risk and that the association remained statistically significant after adjustment for obesity and other potential confounders. Risk increased by about 2.5% for every additional 10 menstrual-cycles. The study also showed that high GRS1 was associated with increased risk. This relationship, however, was attenuated after adjustment for obesity. Our study further indicated women with high TNMC and GRS1 had twice the risk of endometrial cancer compared to those low in both indices. Our results provided additional support to the involvement of estrogen exposure in endometrial cancer risk with regard to genetic background and lifestyle features.
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
Zhanwei
Z
Wang
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, and Yale Cancer Center.
Harvey
H
Risch
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, and Yale Cancer Center.
Lingeng
L
Lu
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, and Yale Cancer Center.
Melinda L
ML
Irwin
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, and Yale Cancer Center.
Susan
S
Mayne
Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT, and Yale Cancer Center.
Peter
P
Schwartz
Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT, and Yale Cancer Center.
Thomas
T
Rutherford
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.|Department of Epidemiology, Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115, USA.
Immaculata
I
De Vivo
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
Herbert
H
Yu
D000293:Adolescent; D000368:Aged; D002648:Child; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004967:Estrogens; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008597:Menstrual Cycle; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D004967:Estrogens