Possible Genetic Predisposition to Lymphedema after Breast Cancer

Possible Genetic Predisposition to Lymphedema after Breast Cancer

Lymphat Res Biol. 2012

Beth Newman, Ph.D.,¹ Felicity Lose, Ph.D.,² Mary-Anne Kedda, Ph.D.,¹ Mathias Francois, Ph.D.,³ Kaltin Ferguson,² Monika Janda, Ph.D.,¹ Patsy Yates, Ph.D.,⁴ Amanda B. Spurdle, Ph.D.,^2,* and Sandra C. Hayes, PhD^1,*

^Abstract

Background

Known risk factors for secondary lymphedema only partially explain who develops lymphedema following cancer, suggesting that inherited genetic susceptibility may influence risk. Moreover, identification of molecular signatures could facilitate lymphedema risk prediction prior to surgery or lead to effective drug therapies for prevention or treatment. Recent advances in the molecular biology underlying development of the lymphatic system and related congenital disorders implicate a number of potential candidate genes to explore in relation to secondary lymphedema.

Methods and Results

We undertook a nested case-control study, with participants who had developed lymphedema after surgical intervention within the first 18 months of their breast cancer diagnosis serving as cases (n=22) and those without lymphedema serving as controls (n=98), identified from a prospective, population-based, cohort study in Queensland, Australia. TagSNPs that covered all known genetic variation in the genes SOX18, VEGFC, VEGFD,VEGFR2, VEGFR3, RORC, FOXC2, LYVE1, ADM, and PROX1 were selected for genotyping. Multiple SNPs within three receptor genes, VEGFR2, VEGFR3, and RORC, were associated with lymphedema defined by statistical significance statistical significance  or extreme risk estimates

Conclusions

These provocative, albeit preliminary, findings regarding possible genetic predisposition to secondary lymphedema following breast cancer treatment warrant further attention for potential replication using larger datasets.

NIH

Lymphedema Genetics

When I originally became active in online groups, blogs and websites, there were only two genes identified as being involved with causing hereditary lymphedema.

Now, eight specific genes have been identified as causing sevweral hereditary lymphedema syndromes and associated syndromes with lymphatic malformations.

At our main website Lymphedema People, we have complete information pages on each one:

Lymphedema Gene CCBE1

Lymphedema Gene FLT4

Lymphedema Gene FOXC2

Lymphedema Gene GATA2

Lymphedema Gene GJC2

Lymphedema Gene KIF11

Lymphedema Gene SOX18

Lymphedema Gene VEGFC

also:

Hereditary Lymphedema

Lymphedema Genetics

Lymphedema Genetics

When I originally became active in online groups, blogs, and websites, there were only two genes identified as being involved with causing hereditary lymphedema.

Now, eight specific genes have been identified as causing several hereditary lymphedema syndromes and associated syndromes with lymphatic malformations or dysplasia.

At our main webste, Lymphedema People, we have complete information pages on each one:

Lymphedema Gene CCBE11

Lymphedema Gene FLT4

Lymphedema Gene FOXC2

Lymphedema Gene GATA2

Lymphedema Gene GJC2

Lymphedema Gene KIF11

Lymphedema Gene SOX18

Lymphedema Gene VEGFC

Spinal extradural arachnoid cysts associated with distichiasis and lymphedema.

Spinal extradural arachnoid cysts associated with distichiasis and lymphedema.

Yabuki S,
Kikuchi SI,
Ikegawa S.

Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.

Spinal extradural arachnoid cysts (SEDAC) are lesions communicating to the subarachnoid space of the spinal canal via a dural defect. SEDAC occupies intraspinal space and sometimes causes neurological disturbances. Although most reported cases are sporadic, several familial cases have been described, suggesting a genetic etiology. Here we report on a family with SEDAC inherited in an autosomal dominant mode. Detailed study showed that the family has the lymphedema-distichiasis syndrome. Among family members examined, a total of ten in two generations manifested all or some of the following features: SEDAC, distichiasis and lymphedema. Seven had spinal cysts, four had both SEDAC and distichiasis, and one had SEDAC distichiasis and lymphedema; three did not have SEDAC.

These findings, together with rarity of both distichiasis and lymphedema in the general population, support that all of the ten members were affected with one clinical entity, the lymphedema-distichiasis syndrome. The distribution of features illustrates the variable expressivity of clinical manifestations.

Although FOXC2 mutation analysis was not performed in our family, it is likely that SEDAC is a component manifestation of lymphedema-distichiasis syndrome and more consistent in our family than those reported. (c) 2007 Wiley-Liss, Inc.

PMID: 17366583 [PubMed - as supplied by publisher]

See Also: LYMPHEDEMA-DISTICHIASIS SYNDROME