Endometrial cancer is the fourth most common cancer in women in this country, according to National Cancer Institute statistics. Progesterone’s important protective role showed up three decades ago, articulated in the unopposed estrogen theory. In the early 1970s, researchers documented that a woman on unopposed estrogen replacement therapy had a 10 times higher chance of endometrial cancer, but adding progesterone reduced the estrogen-associated risk substantially. Now Harvard researchers have found that women with a common variation in the progesterone receptor gene may have nearly double the risk of endometrial cancer. The variant was present in 15 percent of the endometrial cancer cases studied and may confer extra risk in the presence of certain environmental exposures. For example, overweight women with the variant had a five times greater chance of cancer of the cells lining the uterus. “The strength of this study is that it’s one of the few examples where a common variant is associated with a common disease,” said lead author Immaculata De Vivo, a molecular epidemiologist with the Nurses’ Health Study and a Harvard Medical School assistant professor of medicine at Brigham and Women’s Hospital. De Vivo also is a Harvard School of Public Health assistant professor of epidemiology.