Lynch syndrome (HNPCC or hereditary nonpolyposis colorectal cancer; Pic. 1) is an autosomal dominant genetic condition (Pic. 2) that has a high risk of colon cancer. It is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. 

Not everyone with Lynch syndrome will develop bowel cancer. However, a person who inherits a Lynch syndrome mutation has increased risk—generally around 30– to 50% unless preventative measures are taken. Developing bowel cancer at a young age is not uncommon.

In men and women with Lynch syndrome, cancers can also occur in the kidney, ureter (the tube from the kidney to the bladder) and in parts of the gut such as the small bowel (intestine), stomach or pancreas. Women also have an increased risk of cancer of the inner lining of the uterus (womb) and the ovaries.

Early identification of subjects with Lynch syndrome is important because of the early beginning of the disease, the high penetrancy of neoplasms and the efficacy of screening for the different tumors. Close surveillance has demonstrated to reduce the incidence of CRC (colorectal cancers) and the consequent diseases.

Prophylactic hysterectomy with bilateral salpingo-oophorectomy reduces the incidence of endometrial and ovarian cancer in females with Lynch syndrome and must be taken into consideration as an option in women who have completed their reproductive desires. Screening of these tumours is also used, but is less effective than in CRC. The measure with greater net benefit consists in an annual screening beginning at age 30 with prophylactic surgery at age 40. Despite there is little evidence about the effectiveness of screening for other tumours associated to Lynch syndrome, NCCN (National Comprehensive Cancer Network guidelines) recommends some options depending on the clinical needs.

Education of patients as well as physicians about all facets of this disorder is extremely important. If patients are to show compliance with germ-line testing, screening, and management options, they must understand the natural history and the significance of their genetic risk status. Physicians must also be aware of clinical nuances of this disorder to provide the necessary care.


LS doesn't cause any symptoms.

Associated diseases

  • colon cancer
  • endometrial cancer (second most common)
  • other cancers including ovary, stomach, small intestine, hepatobiliary tract (essential for digestion), upper urinary tract, brain, and skin


Risk of cancer

Individuals with HNPCC have about an 80% lifetime risk for colon cancer. Two-thirds of these cancers occur in the proximal colon. Also, women with HNPCC have an 80% lifetime risk of endometrial cancer. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer, making endometrial cancer the most common sentinel cancer in Lynch syndrome. In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40. Other HNPCC-related cancers have been reported with specific features: the urinary tract cancers are transitional carcinoma of the ureter and renal pelvis; small bowel cancers occur most commonly in the duodenum and jejunum; the central nervous system tumor most often seen is glioblastoma.

Risk factors 

So far, four different genes have been found to be associated with Lynch syndrome: hMLH1, hMSH2, hMSH6 and PMS2. A mutation in one of these genes can cause Lynch syndrome.
Relying solely on age and family history based criteria inaccurately identifies eligibility for Lynch syndrome screening or testing in 25%–70% of cases.


Genetic testing involves a blood test. The initial genetic testing in a family (called a mutation search) must be done in someone in the family who has developed a Lynch syndrome cancer. If a mutation is identified in that person, other relatives at risk of carrying the mutation can then be tested.
If the family mutation is not found, genetic testing is not able to be offered to other family members. If a family mutation is found, the rest of the family can be offered predictive testing (types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life).

Many cancer treatments affect fertility. Cancer surgery may have impact in fertility by removing reproductive organs or damaging structures needed for reproduction. Chemotherapy and radiotherapy have toxic effects on the gonads and may in certain cases induce ovarian and testicular failure, affecting thus all aspects of reproductive health, including pubertal development, impairment of hormone production and sexual function in adults.

With regard to cancer risk in relation to the cause of subfertility, the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on fertility drugs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal.

The link between ovarian cancer and fertility drugs has not been established and fertility therapy does not increase the risk of ovarian cancer in infertile patients who already have an increased baseline risk as a result of their infertility.

Fertility-sparing surgery may be an option for selected patients who wish to retain the ability to achieve a pregnancy. In many cases, pregnancies will occur spontaneously, nevertheless, causes of subfertility may be present in some patients, and a number of those may further require assisted reproduction treatments. In gynecologic and urologic oncologic surgery, there has been a gradual development of fertility-sparing surgery aiming at preserving reproductive organs without compromising survival. Indications for fertility-sparing surgery include, in general, a well-differentiated low-grade tumor in its early stages or with low malignant potential.

Find more about related issues


Hereditary nonpolyposis colorectal cancer ―sourced from Wikipedia licensed under CC BY-SA 3.0
Lynch syndrome ―sourced from Cancer Institute NSW licensed under CC BY 4.0
Lynch Syndrome: An Updated Review ―by Sehgal et al. licensed under CC BY 3.0
Predictive testing ―sourced from Wikipedia licensed under CC BY-SA 3.0
Autosomal Dominant Pedigree Chart ―by Walker licensed under CC BY-SA 3.0
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