Selective breeding of the domestic dog (Canis lupus familiaris) rigidly retains desirable features, and could inadvertently fix disease-causing variants within a breed. We combine phenotypic data from > 72,000 dogs with a large genotypic dataset to search for genes associated with cancer mortality and longevity in pedigree dog breeds. We validated previous findings that breeds with higher average body weight have higher cancer mortality rates and lower life expectancy. We identified a significant positive correlation between life span and cancer mortality residuals corrected for body weight, implying that long-lived breeds die more frequently from cancer compared to short-lived breeds. We replicated a number of known genetic associations with body weight (IGF1, GHR, CD36, SMAD2 and IGF2BP2). Subsequently, we identified five genetic variants in known cancer-related genes (located within SIPA1, ADCY7 and ARNT2) that could be associated with cancer mortality residuals corrected for confounding factors. One putative genetic variant was marginally significantly associated with longevity residuals that had been corrected for the effects of body weight; this genetic variant is located within PRDX1, a peroxiredoxin that belongs to an emerging class of pro-longevity associated genes. This research should be considered as an exploratory analysis to uncover associations between genes and longevity/cancer mortality.

家犬（犬狼疮）的选择性繁殖严格地保留了理想的特征，并且可能无意中修复了一个品种内的致病变异。我们将来自 > 72,000 只狗的表型数据与大型基因型数据集相结合，以在纯种犬种中搜索与癌症死亡率和寿命相关的基因。我们验证了之前的研究结果，即平均体重较高的品种具有较高的癌症死亡率和较低的预期寿命。我们发现寿命和癌症死亡率残差之间存在显着的正相关，根据体重校正，这意味着与寿命短的品种相比，长寿品种死于癌症的频率更高。我们复制了许多已知的与体重相关的遗传关联（IGF1、GHR、CD36、SMAD2和IGF2BP2）。随后，我们在已知的癌症相关基因（位于SIPA1、ADCY7和ARNT2 内）中鉴定了五种遗传变异，这些变异可能与针对混杂因素校正的癌症死亡率残差相关。一种推定的遗传变异与已针对体重影响校正的长寿残差略有显着相关；该遗传变异位于PRDX1内，PRDX1 是一种过氧化物氧还蛋白，属于一类新兴的促长寿相关基因。这项研究应被视为探索性分析，以揭示基因与长寿/癌症死亡率之间的关联。