Gynecologic Cancer and Colorectal Cancer

The last thing a cancer survivor wants to think about, let alone go through, is another cancer. Unfortunately, an estimated 14% of cancer survivors are reported to develop a second primary malignancy (SPM) within 25 years of their first cancer diagnosis. Of the diagnosed second primary malignancies, colorectal cancer is the most common after lung cancer, accounting for 12% of all SPM.

One of the prominent risk factors that increases the likelihood of being diagnosed with colorectal cancer as a SPM is gynecologic cancer. Gynecologic cancer is a catch-all term for cancer of the female reproductive organs, such as the cervix, ovaries, uterus, vagina and vulva. Of these cancers, patients diagnosed with uterine and, to a lesser extent, ovarian cancer are at risk of developing colorectal cancer years after their first diagnosis.

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Uterine cancer (sometimes called womb cancer) is the fourth most common cancer affecting women in the United States, and the yearly diagnoses continue to rise in both older women and women below 50.

In uterine cancer, cancer cells form in the uterus or womb tissue, and can be broadly classified into two types — endometrial cancer and uterine sarcoma, with the latter being the rarer form. In the case of the more common endometrial cancer, cancerous growth begins in the endometrium, the lining of the uterus.

Ovarian cancer, on the other hand, impacts the ovaries. While ovarian cancer typically affects older women between the ages of 50 and 64, those who carry mutations in the BRCA1 and BRCA2 genes.

Ovarian cancer can be classified into three types — the more commonly occurring epithelial ovarian cancer and the rare stromal and germ cell ovarian tumors that are usually diagnosed at an earlier age.

One of the reasons why the risk of developing colorectal cancer after first being diagnosed with gynecologic cancer is due to a commonality in pathogenesis. This is especially true for individuals who have also been diagnosed with Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC).

Lynch syndrome is an autosomal dominant germline mutation in DNA mismatch repair genes. It is a familial syndrome that can be passed down the generations and predisposes individuals to colorectal cancer and other cancers, including endometrial, ovarian, stomach, liver, kidney, brain and certain types of skin cancers.

Those diagnosed with Lynch syndrome are at risk of developing cancer at an earlier age, averaging at 45 years. In women, the risk of endometrial cancer exceeds that of colorectal cancer, with endometrial cancer more likely to be diagnosed before colorectal cancer in half the women with Lynch syndrome.

A small study found results consistent with the well-established relationship between uterine and colorectal cancer. Out of 127 women with Lynch syndrome and originally diagnosed with uterine cancer, about 20% of these women were diagnosed with colorectal cancer during a 10-year follow-up, and 48% developed colorectal cancer within 20 years of the initial uterine cancer diagnosis (compared to a 39.9% risk for the general population).

The risk of developing colorectal cancer after ovarian cancer remains significant and in fact greatly impacts ovarian cancer patients at higher rates compared to the endemic population. Particularly for women below 60, the incidence of second primary cancers in the breasts, ascending colon and transverse colon increases.

Nonetheless, the connection between uterine and colorectal cancer in Lynch syndrome carriers is so pervasive that women diagnosed with endometrial or ovarian cancer before the age 60 are recommended colorectal cancer screening from age 40 onwards or when the gynecological tumor is first diagnosed.

Another contributor to colorectal cancer as a second primary malignancy following uterine cancer is the use of radiation therapy as treatment.

While surgery is often the primary treatment for uterine and ovarian cancer, it is also used in combination with other therapies, such as radiation therapy or chemotherapy, to eliminate cancer cells from the body. Though radiation therapy can be effective in killing cancer cells, other cells that are exposed to radiation can also develop mutations and become cancerous.

The colon’s relative proximity to the uterus and ovaries results in greater radiation exposure compared to other organs, such as the lungs and breasts. Based on data of over 31,000 patients from the Surveillance, Epidemiology, and End Results (SEER) database, one study found that the variation in radiation dosage, exposure duration and tissue type had different results on cells. While a lethal dosage produced the required anti-cancer effect, radiation at sublethal or lower doses possibly had tumor inducing effects instead.

The assertion that radiation therapy has a direct influence on the risk of developing SPM is further supported by the results of a separate study, which found that the incidence of a second cancer was higher in gynecologic cancer patients who received radiation therapy compared to those who received only surgical treatment.

Unlike diet and lifestyle related colorectal cancer risk factors, managing uterine or ovarian cancer not only as a disease but as a colorectal cancer risk factor is more complicated and cannot be done without targeted or medical intervention.

As present research draws strong associations between gynecologic cancer and second primary colorectal cancer, the implications of these findings should be taken into consideration when counseling uterine cancer patients. Patients should be advised on the risks of radiation therapy and the future risks it presents, and also be recommended regular colorectal cancer screening, especially for those diagnosed with Lynch syndrome.

If you are currently battling uterine or ovarian cancer or have received treatment for it, the last thing you would hope to experience is this worst-case scenario of being diagnosed with another cancer. Nonetheless, we hope that by shedding light on the associated risks, you can better understand the options available to you should the worst come to pass.