Abstract
BackgroundOver half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include endometrial and ovarian cancers. The benefits of surveillance for gynecological cancers are not yet proven and there is no consensus on the optimal surveillance recommendations for women with MMR mutations.MethodsWe performed a systematic review of the literature and evaluated gynecological cancer risk in a series of 631 Polish HNPCC families classified into either Lynch Syndrome (LS, MMR mutations detected) or HNPCC (fulfillment of the Amsterdam or modified Amsterdam criteria).ResultsPublished data clearly indicates no benefit for ovarian cancer screening in contrast to risk reducing surgery.We confirmed a significantly increased risk of OC in Polish LS families (OR = 4,6, p < 0.001) and an especially high risk of OC was found for women under 50 years of age: OR = 32,6, p < 0.0001 (95% CI 12,96-81,87). The cumulative OC risk to 50 year of life was calculated to be 10%. Six out of 19 (32%) early-onset patients from LS families died from OC within 2 years of diagnosis. We confirmed a significantly increased risk of EC (OR = 26, 95% CI 11,36-58,8; p < 0,001). The cumulative risk for EC in Polish LS families was calculated to be 67%.ConclusionsDue to the increased risk of OC and absence of any benefit from gynecological screening reported in the literature it is recommended that prophylactic oophorectomy for female carriers of MMR mutations after 35 year of age should be considered as a risk reducing option. Annual transvaginal ultrasound supported by CA125 or HE4 marker testing should be performed after prophylactic surgery in these women.Due to the high risk of EC it is reasonable to offer, after the age of 35 years, annual clinical gynecologic examinations with transvaginal ultrasound supported by routine aspiration sampling of the endometrium for women from either LS or HNPCC families. An alternative option, which could be taken into consideration for women preferring surgical prevention, is risk reducing total hysterectomy (with bilateral salpingo-oophorectomy) for carriers after childbearing is complete.Electronic supplementary materialThe online version of this article (doi:10.1186/s13053-015-0025-2) contains supplementary material, which is available to authorized users.
Highlights
Over half the cancer deaths in hereditary nonpolyposis colorectal cancer (HNPCC) families are due to extra-colonic malignancies that include endometrial and ovarian cancers
It has been shown that Lynch Syndrome (LS) is a result of germline mutations in genes involved in DNA mismatch repair (MMR) MSH2, MLH1, MSH6, and PMS2, whereas as HNPCC refers to families that adhere to the Amsterdam criteria or iterations of it
During 2002-2014 631 HNPCC families studied were classified into either LS or HNPCC at the International Hereditary Cancer Center (IHCC) Szczecin, Poland, due to 1): identification of pathogenic MMR gene mutations -278 LS families (1176 women, 1507 men); or 2): fulfillment of Amsterdam criteria (144 families, 240 affected individuals and 750 their first-degree relatives) or HNPCC suspected criteria – total 353 families referred as HNPCC families (1285 females, 1145 males)
Summary
Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include endometrial and ovarian cancers. Mutation carriers are at high risk of developing colorectal cancer (CRC), and endometrial cancer (EC) at unusually young ages [8]. Due to the high cumulative risk of CRC colonoscopy is recommended in LS families [11]. The aim of this study was to perform a systematic review of the literature and to evaluate and compare cancer risk in our series of 631 Polish HNPCC families including 279 families with identified mismatch repair (MMR) gene mutations (referred as Lynch syndrome (LS) families) in order to suggest optimal management of ovarian and endometrial cancer for female MMR mutation carriers and their close relatives
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