Risk of Prostate Cancer in Lynch Syndrome: A Systematic Review and Meta-analysis

Ryan, Shae; Jenkins, Mark A.; Win, Aung Ko

doi:10.1158/1055-9965.epi-13-1165

Cited by 110 publications

(67 citation statements)

References 49 publications

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“…Several studies have demonstrated increased risk of prostate cancer with mutations in known prostate cancer susceptibility genes (Table ) . Although conventional opinion has held that the prevalence of patients with prostate cancer harboring germline alterations was quite low, recent data challenge that notion.…”

Section: Genetic Basis Of Prostate Cancer Predispositionmentioning

confidence: 99%

Genetic testing for hereditary prostate cancer: Current status and limitations

Zhen

Syed

Nguyen

et al. 2018

Cancer

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A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next-generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM-mutated, metastatic, castrate-resistant prostate cancer, it is being recognized that the results of genetic testing have an impact on therapeutic strategies. In this review, the authors examine the role of genetic counseling and testing, the challenges of insurance coverage for testing, the available germline and somatic testing panels, and the complexity of each testing method and its implications. Cancer 2018. © 2018 American Cancer Society.

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Section: Genetic Basis Of Prostate Cancer Predispositionmentioning

confidence: 99%

Genetic testing for hereditary prostate cancer: Current status and limitations

Zhen

Syed

Nguyen

et al. 2018

Cancer

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“…Several studies have found the lifetime risk for prostate cancer in Lynch syndrome to be increased by two-to five-fold 75–77. Additional studies are needed to determine whether Lynch syndrome-associated prostate cancers occur at an earlier average age or are more aggressive 75,76…”

Section: Clinical Spectrum Of Lynch Syndromementioning

confidence: 99%

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

Cohen¹,

Leininger²

2014

TACG

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Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers.

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“…Lynch syndrome is an autosomal dominant inherited disorder of cancer susceptibility caused by a heterozygous germline mutation in one of the MMR genes [2] or a deletion in the 3' end of the EPCAM gene, which leads to epigenetic silencing of the closely linked MSH2 3]. Carriers of a heterozygous MMR gene mutation are at increased risk of multiple adult cancers, most notably colorectal and endometrial cancer, but also cancer of the stomach, ovary, ureter, renal pelvis, brain, small bowel, and hepatobiliary tract [4], as well as breast [5] and prostate [6]. The development of these cancers generally occurs in mutation carriers at a younger age than in the general population.…”

Section: Introductionmentioning

confidence: 99%

Childhood cancers in families with and without Lynch syndrome

et al. 2015

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Background Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes or the EPCAM gene is associated with an increased risk of colorectal cancer, endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of childhood cancers in Lynch syndrome families, however, is not well studied. Materials and Methods Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR-proficient colorectal cancer (non-Lynch syndrome families). Results There was no evidence of a difference in the proportion of relatives with a childhood cancer between Lynch syndrome families (41/17,230; 0.24 %) and non-Lynch syndrome families (179/94,302; 0.19 %; p = 0.19). Incidence rate of all childhood cancers was estimated to be 147 (95 % CI 107–206) per million population per year in Lynch syndrome families and 115 (95 % CI 99.1–134) per million population per year in non-Lynch syndrome families. There was no evidence for a substantial increase in the risk of all childhood cancers, hematologic cancers, brain and central nervous system cancers, Lynch syndrome-associated cancers, or other cancers in Lynch syndrome families compared with non-Lynch syndrome families. Larger studies, however, are required to more accurately define the risk of specific individual childhood cancers in Lynch syndrome families. Conclusion The risk of childhood cancers does not appear to be significantly increased in Lynch syndrome families compared with non-Lynch syndrome families. Larger studies, however, are required to more accurately define the risk of specific individual childhood cancers in Lynch syndrome families.

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Risk of Prostate Cancer in Lynch Syndrome: A Systematic Review and Meta-analysis

Cited by 110 publications

References 49 publications

Genetic testing for hereditary prostate cancer: Current status and limitations

Genetic testing for hereditary prostate cancer: Current status and limitations

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

Childhood cancers in families with and without Lynch syndrome

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