Assignment: Research endometrial and colon cancer (Lynch Syndrome)

 

Lynch Syndrome

• Endometrial cancer is the most common of the gynecologic cancers. Fortunately, most women will survive their initial diagnosis, making this the largest group of survivors who had a gynecologic malignancy.
• However, most patient will develop a second type of cancer and the majority of recurrence occur within three years after the treatment. Most common second type cancers are Colon and breast cancers
• There is a specific population, who are in increases risk of both endometrial and colon cancer. These population have an autosomal dominant condition known as Lynch syndrome. Lynch syndrome is associated with early onset of cancer and, particularly colon and endometrial cancer. Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.
• In overall population, Lynch Syndrome associated with a 22–75% lifetime risk of colorectal carcinoma and a > 30% lifetime risk of endometrial cancer
• Especially in women, Lynch syndrome has 40-50% estimated risk of developing colon cancer and there is even higher risk of developing endometrial cancer.
• A research included 117 women with Lynch syndrome showed that 61% were diagnosed with endometrial cancer first before developing colorectal cancer.
• Therefore, gynecologic oncologists need to actively identify of Lynch syndrome among their patients because most women are first diagnosed with endometrial cancer.
• Providers caring for women with endometrial cancer should obtain a through personal and family history in order to determine the need of genetic evaluation
• In general, Genetic evaluation is recommended for those with a
  • personal or family history of colorectal cancer under age 50
  • a history of multiple family members with cancer
  • greater than 5% PREMM5 model-predicted chance of Lynch syndrome
    • The PREMM5 model is a clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes. Mutations in these genes cause Lynch syndrome, an inherited cancer predisposition syndrome.
  • Because personal and family history alone are insufficient to identify a significant proportion of patients with Lynch syndrome, the National Comprehensive Cancer Network recommends that allcolorectal cancers should undergo testing for Lynch syndrome
  • There are a great benefit in identifying Lynch syndrome early because Lynch-associated endometrial cancer survivors should undergo colorectal cancer screening, which can help to detect the disease early.

 

Screening recommendation  Lynch- syndrome

• Colonoscopy screening in every 1-2 years beginning at age 20-15 years prior to the youngest age of cancer diagnosis in the family. For MSH6 families the screening begins at age 30
• Endometrial aspiration or transvaginal ultrasound screening for endometrial cancer in women beginning at age 25–35 years
• Consider screening for gastric cancer with upper endoscopy every 2–3 years beginning at age 30–35 years

Prophylactic Treatment

• Consider prophylactic hysterectomy and oophorectomy in women at age 40 or once they have finished childbearing
• Subtotal colectomy with ileorectal anastomosis if cancer is found (followed by annual surveillance of the rectal stump)
• Family members who have not yet been diagnosed with any cancers should undergo screening for both endometrial cancer and colorectal cancer and may also benefit from prophylactic hysterectomy and bilateral salpingo-oophorectomy

 

Conclusion:

Overall, A diagnosis of Lynch syndrome provides an opportunity to utilize screening and prevention strategies that may decrease the incidence and mortality.

 

• Aside from Lynch syndrome population, I found a retrospective analysis published on Journal of clinical oncology that looked at the prevalence of developing colorectal cancer after diagnosing with endometrial cancer.
• The analysis included 3,115 women with endometrial cancer and a matched control group of 15,084 women who did not have endometrial cancer. The study population had a cumulative follow-up of 145,502 person-years.
• According to this study a history endometrial cancer younger than 50 quadrupled the likelihood of a subsequent diagnosis of colorectal cancer. And most of these second cancer are right-sided colorectal cancer
• The risk of right-sided colorectal cancer increased more than sevenfold among women whose endometrial diagnosis occurred at age 50 or younger (HR 7.48, 95% CI 1.29 to 43.28) and was more than doubled in women 51 to 65 at diagnosis of endometrial cancer
• Therefore, the author of the article, Harminder Singh suggest “Colorectal cancer screening with colonoscopy should be considered soon after diagnosis of endometrial cancer for all women.”

 

Sources:

1. https://www.cancer.org/cancer/endometrial-cancer/after-treatment/second-cancers.html
2. https://www.medpagetoday.com/meetingcoverage/acg/35545
3. Risk of Colorectal Cancer After Diagnosis of Endometrial Cancer: A Population-Based Study (journal of clinical oncology)
4. https://ascopubs.org/doi/full/10.1200/JCO.2012.47.6481?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&
5. Meyer, L. A., Broaddus, R. R., & Lu, K. H. (2009). Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer control : journal of the Moffitt Cancer Center, 16(1), 14–22. https://doi.org/10.1177/107327480901600103