Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database

Abstract

ObjectiveToday most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers?DesignInformation was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants.Results1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%).ConclusionsRelative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94–1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer.

Physical activity and the risk of colorectal cancer in Lynch syndrome

“…[2][3][4] People with Lynch syndrome are predisposed to a variety of cancers, in particular colorectal cancer, having on average a risk to age 70 years of 20-50% depending on the sex of the person and the gene mutated. [5][6][7][8][9][10] There is substantial variation in age-specific cancer risk (penetrance) in mutation carriers, consistent with a modifying effect of genetic, environment and lifestyle behaviors on cancer risk. 6 Lifestyle factors such as smoking, alcohol consumption, body mass index (BMI) and use of aspirin and supplements have been shown to be associated with altered risk of colorectal and endometrial cancer for people with Lynch syndrome.…”

“…2 Age at diagnosis of colorectal cancer for affected participants; age at diagnosis of another cancer or polypectomy or interview for colorectal cancer-unaffected participants (whichever came first); 3 Average daily ethanol intake was calculated as weighted average of daily ethanol intake from any alcoholic beverage when carriers were in their 20, 30 and 40 sec and 50 sec and above; 4 Former smokers defined as carriers who had smoked at least one cigarette per day for at least 3 months and had quit >2 years before age at colorectal cancer or censored age; current smokers defined as carriers who had smoked at least one cigarette per day for at least 3 months and continued within 2 years of age at colorectal cancer or censored age; 5 Underweight <18.5 kg/m 2 , normal (18.5-<25.0) kg/m 2 , overweight (25.0-<30 kg/m 2 ), obese (30 kg/m 2 ); 6 Carriers who were diagnosed with colorectal cancer or censored >2 years before interview had missing for this variable. 7 A serving of fruit defined as 1 medium fresh fruit, or 1 =2 cup of chopped, cooked or canned fruit or 1 =4 cup of dried fruit or 6 ounce of fruit juice; a serving of vegetable defined as 1 cup raw leafy vegetables or 1 =2 cup of other vegetables, or cooked or chopped raw, 6 ounces of vegetable juice; 8 A serving of red meat defined as 2-3 ounces of red meat, or a piece of meat about the size of a deck of cards. 9 At least twice a week; 10 yielded similar results to our primary analysis (details not shown).…”

Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes

“…Often this is related to a better prognosis in both the patient and his/her family as also other family member could have inherited the genetic predisposition causing the syndrome. In addition, patients with hereditary cancer can benefit from a treatment adapted to the hereditary predisposition [14–18]. …”

Hereditary Pancreatic Cancer

“…Lynch syndrome can also occur because of loss of expression of MSH2 due to deletion in the EPCAM gene [20]. Typical affected family members of lynch have an increased risk of colon cancer but are at risk for several other malignancies, including pancreatic cancer [21]. [25].…”