Ge­netic Test: Squa­mous Cell Car­ci­noma

Practical Horseman - - Health Update -

Squa­mous cell car­ci­noma is the sec­ond most com­mon type of equine tu­mor and the most fre­quent tu­mor of the horse’s eye, ac­cord­ing to a re­port on re­search led by Re­becca R. Bel­lone, PhD, from the Univer­sity of Cal­i­for­nia Davis School of Vet­eri­nary Medicine and the Vet­eri­nary Ge­net­ics Lab­o­ra­tory. SCC can lead to vi­sion im­pair­ment and the loss of an eye and can spread into the or­bital bone and the brain, po­ten­tially turn­ing fa­tal.

Ge­net­ics seem to be a risk fac­tor for the dis­ease since sev­eral breeds, in­clud­ing Haflingers, tend to ex­pe­ri­ence a higher oc­cur­rence. Dr. Bel­lone and her team, in­clud­ing UC Davis vet­eri­nary oph­thal­mol­o­gist Mary Las­saline, DVM, PhD, MA, DACVO, set out to in­ves­ti­gate this ge­netic link. Their study in­cluded 67 Haflingers—43 iden­ti­fied as af­fected by SCC and the oth­ers un­af­fected. The re­search team ex­am­ined five-gen­er­a­tion pedi­grees for all 67 horses, look­ing for a com­mon an­ces­tor who would sup­port the the­ory of a ge­netic link. They found one. Ex­am­in­ing the re­la­tion­ship be­tween af­fected and un­af­fected horses showed that the ge­netic link was most likely in­her­ited as a re­ces­sive trait, says Dr. Bel­lone.

Re­searchers used this in­for­ma­tion to guide their next step: a genome-wide study where they in­ves­ti­gated ap­prox­i­mately 65,000 ge­netic mark­ers. They found that risk for SCC was as­so­ci­ated with mark­ers on chro­mo­some 12 and, specif­i­cally, a risk vari­ant of gene DDB2, says Dr. Bel­lone. DDB2 is a pro­tein needed to re­pair UV dam­age to DNA. The team’s work­ing hy­poth­e­sis (cur­rently be­ing tested) is that the risk vari­ant they iden­ti­fied “im­pairs the abil­ity of this pro­tein to rec­og­nize DNA that is dam­aged, thus the dam­age can’t be re­paired and that leads to cancer,” says Dr. Bel­lone.

The re­searchers fur­ther de­ter­mined that horses who are ho­mozy­gous for the risk fac­tor (they’ve in­her­ited it from both sire and dam) are 5½ times more likely to de­velop SCC than those with one copy or no copies of the risk fac­tor.

The Vet­eri­nary Ge­net­ics Lab­o­ra­tory used these find­ings to de­velop a ge­netic test for the SCC risk fac­tor in Haflingers. (To learn more, visit https://www.vgl.uc­­vices/HaflingerSCC.php.)

While not all cases of SCC can be linked to ge­net­ics, this study shows they play a sig­nif­i­cant role, par­tic­u­larly in the Haflinger breed. This knowl­edge, along with the new ge­netic test, can help own­ers as­sess the risk their own horses face and help them make more in­formed breed­ing de­ci­sions.

The vari­ant was also found in Bel­gian and Percheron horses, and the re­searchers are now work­ing to de­ter­mine if it’s a risk fac­tor for these breeds, too.

In­ter­est­ingly, a sim­i­lar dis­ease in hu­mans has also been linked to DDB2. So in­sights from the equine study may lead to new in­for­ma­tion for hu­man health as well.

A New Un­der­stand­ing Of Sad­dle Fit

You know that sad­dle fit in­flu­ences your horse’s com­fort and per­for­mance. But new re­search shows that even es­tab­lished in­dus­try fit­ting stan­dards may need some tweak­ing to bet­ter al­le­vi­ate back pres­sure and im­prove gaits.

That’s the bot­tom-line find­ing of re­search led by Rachel Mur­ray, VetMB, MS, PhD, MRCVS, Dip ACVS, as­so­ciate of Euro­pean Col­lege of Vet­eri­nary Di­ag­nos­tic Imag­ing, who works at Eng­land’s An­i­mal Health Trust. Specif­i­cally, Dr. Mur­ray and col­leagues com­pared pres­sure, limb pro­trac­tion, knee and hock flex­ion, and back width be­tween sad­dles fit­ted to in­dus­try guide­lines and one spe­cially de­signed to re­duce pres­sure along ei­ther side of the tho­racic ver­te­brae known as T10 to T13. (Pre­vi­ous re­search had shown that a horse’s back, or tho­ra­colum­bar, width in­creases af­ter ex­er­cise when his sad­dle fits prop­erly as well as when horses are rid­den more cor­rectly with a more skilled rider.)

The study in­cluded 13 in­ter­na­tional-level dres­sage horses, aged 8 to 16 years, with no ex­ist­ing lame­ness or per­for­mance prob­lems. They were each rid­den in the study by their usual pro­fes­sional riders. For the con­trol por­tion of the test, they were rid­den in their nor­mal sad­dles, which were eval­u­ated and fit­ted by four qual­i­fied sad­dle fit­ters.

The test sad­dles had mod­i­fi­ca­tions over typ­i­cal sad­dles. The tree shape, align­ment of the girth bil­lets and shape of the pan­els were ad­justed to ac­com­mo­date the horse’s mus­cu­la­ture (tho­ra­colum­bar ex­pan­sion)

dur­ing ex­er­cise ver­sus while stand­ing. The solid arm of the panel was short­ened to re­duce the area of po­ten­tial re­stric­tion at the front of the sad­dle and the stir­rup bars were at­tached to the ex­te­rior of the tree. The pan­els were lined with pres­sure­ab­sorb­ing ma­te­rial.

Re­searchers used a pres­sure mat un­der the sad­dle pan­els as well as high­speed mo­tion cap­ture to eval­u­ate the ef­fect of the two sad­dles on the horses while be­ing rid­den at sit­ting trot. In ad­di­tion, the tho­ra­colum­bar width was mea­sured be­fore and af­ter ex­er­cise.

The re­searchers found that peak pres­sures were sig­nif­i­cantly less with the test sad­dles than the con­trol sad­dles. In ad­di­tion, the test sad­dles al­lowed greater limb pro­trac­tion as well as greater knee and hock flex­ion. The post-ex­er­cise tho­ra­colum­bar width was also sig­nif­i­cantly greater with the test sad­dles.

Dr. Mur­ray ex­plains that the most sig­nif­i­cant take­away from the study is the un­der­stand­ing that when a horse works cor­rectly, his back ex­pands un­der the sad­dle. “If the sad­dle does not al­low this ex­pan­sion/lift, the horse will be dis­cour­aged from work­ing cor­rectly and en­cour­aged to work with a hol­low, po­ten­tially dipped back, which can af­fect the move­ment of the fore­limbs and hind limbs as well as re­strict back move­ment,” she says.

Stan­dard sad­dle-fit­ting guide­lines don’t nec­es­sar­ily take this into ac­count. There­fore, she adds, it’s im­por­tant to as­sess sad­dle fit not sim­ply when the horse is stand­ing still, but also dur­ing ex­er­cise. — Sushil Du­lai Wen­holz

Re­searchers have dis­cov­ered that ge­net­ics play a key role in the risk fac­tor for squa­mous cell car­ci­noma in sev­eral breeds, in­clud­ing Haflingers.

A re­cent study showed the im­por­tance of as­sess­ing your horse’s sad­dle fit when he’s mov­ing, not just while he’s stand­ing still.

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