Lynch Syndrome: A New Hope in Cancer Prevention with Vaccines

Dr. Stacy Norton was merely seven when her mother succumbed to colon cancer, a tragedy not isolated to her family members who faced aggressive cancers young. Years later, Norton participated in testing a new vaccine potentially shielding her and her offspring from cancer. Norton is one of around 1 million Americans with Lynch syndrome, a hereditary genetic fault increasing their colorectal cancer risk and susceptibility to certain other cancers. They are advised to undergo annual colonoscopies, more frequent than usual, to detect and remove precancerous polyps.

Researchers are developing new vaccines aiming to preemptively train the immune system to halt colon cancer progressions caused by Lynch syndrome before they evolve into tumors. There are at least three possible vaccines under development: two in early clinical trials in the U.S. and a third starting in Britain. The vaccine Norton tested looks promising, with Dr. Eduardo Vilar-Sanchez from MD Anderson Cancer Center predicting a new extensive study next year.

“This is a motivation,” expressed Norton, working at Houston Methodist Willowbrook Hospital. Surviving a Lynch-caused cancer herself and having mutation-inheriting children, she adds, “This vaccine, if successful, might spare them from endless annual colonoscopies.”

Lynch syndrome stems from an inherited genetic mutation. Humans possess mismatch-repair genes, similar to spellcheckers for fixing DNA errors during cell multiplication processes. In Lynch syndrome, one gene fails in its repair role, leading to abnormal build-ups often resulting in tumors before age 50. Colorectal cancer stands as the most frequent outcome. Normal individuals have a 5% risk of developing colorectal cancer in their lives; Lynch carriers face up to 80% risk, depending on their affected gene, according to Vilar-Sanchez.

Another significant risk is endometrial cancer. Lynch carriers have increased chances of developing pancreatic, stomach, ovarian, and certain skin cancers, and a type of brain tumor which claimed Norton’s sister at 25. The realization of her Lynch syndrome came in her 40s after gene testing, confirming why her mother’s side endured colon cancer. Consequently, she transitioned from infrequent to annual colonoscopies. As a gynecologist aware of Lynch’s dangers, Norton preemptively underwent a hysterectomy, which unveiled early-stage cancer in her uterus.

Potential Vaccines for Genetic Cancer Prevention

Existing vaccines like HPV and hepatitis B prevent virus-induced cancers. Developing vaccines for genetic cancer prevention demands complex solutions since they must alert the body about internal tumor-causing mechanisms rather than external virus threats.

Dr. Vilar-Sanchez mentioned that Lynch growths accumulate mutations producing proteins foreign to normal cells, and “Training the immune system to identify these proteins is possible.” Norton and 44 other Lynch carriers trialed a Swiss biotech Nouscom vaccine designed to detect 209 mutations in Lynch precancers. The study observed heightened T-cell activity eliminating tumors with subsequent colonoscopies finding fewer precancerous growths and no advanced polyps, as reported in ‘Nature Medicine.’

Dr. John Marshall, an oncologist at Georgetown University, said, “Stimulating the immune system to counteract Lynch tumors seems feasible, as the study implies.”

For the first time since 2014, Norton’s post-vaccination colonoscopies showed zero polyps after one and two years. She is also part of a subgroup receiving booster shots annually, with more data anticipated this fall.

Oxford University initiates trials for a vaccine against Lynch-induced precancers, made by Massachusetts-based Moderna employing the mRNA platform from its COVID-19 vaccine. In parallel, researchers await results from ImmunityBio’s larger study, ticking California-based vaccine targeting different cancer markers compared to placebo.

Lynch Syndrome and Rising Young Adult Colon Cancer

The U.S. sees about 158,000 annual colorectal cancer cases, predominantly in older adults. Younger adult cases are rising for unclear reasons. Lynch syndrome affects 1 in 279 people. While many remain unaware, more individuals might be learning about receiving care, Vilar-Sanchez stated, given increasing genetic consultations in families with history or cases at young ages, revealing risks to relatives.

Standard guidelines recommend regular colorectal screening starting at age 45 for the general public. Still, any age warrants medical attention for symptoms like blood in stool, rectal bleeding, persistent bowel changes, unexplained weight loss, or abdominal discomfort.

The Health and Science Department of The Associated Press is funded by the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP retains full editorial control of the content.