Risk Model for Prostate Cancer Using Environmental and Genetic Factors in the Spanish Multi-Case-Control (MCC) Study

Abstract

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model.

Dietary Zinc and Risk of Prostate Cancer in Spain: MCC-Spain Study

“…In Asturias and Huelva provinces, participants did not have DNA due to logistical reasons, and were not included in these analyses. We constructed a polygenic risk score (PRS), as explained in detail elsewhere [2]. In summary, we used Genomebrowser [26] to identify those genetic variants associated with PC through GWAS in the population with European ancestry, with PC as “reported trait” and a p-value threshold of 5 × 10 8 .…”

“…We could finally locate in our data 56 of these SNPs. The PRS score was obtained by adding the number of copies of the risk allele of each SNP, weighted by their beta coefficients, obtained from logistic regression analyses [2].…”

“…Prostate cancer (PC) is the most frequent malignant neoplasm among European men, apart from non-melanoma skin cancer [1]. Unfortunately, neither the known genetic susceptibility [2,3] nor the main risk factors -age, race or familial history of PC- are modifiable, while the potential implications of environmental exposure in its aetiology, including the role of diet, remains uncertain [4]. Among the nutrients that have raised specific interest in this field, zinc occupies a major position.…”

Targeted Mass Spectrometry of a Clinically Relevant PSA Variant from Post‐DRE Urines for Quantitation and Genotype Determination

“…[14] There are multiple reports of various singlenucleotide polymorphisms (SNPs) correlating with serum PSA levels. [15][16][17][18][19][20] One SNP that repeatedly shows this connection is rs17632542 on chromosome 19 in the kallikrein-3 gene leading to lower serum PSA levels than expected. [17][18][19][21][22][23] The genetic variant alters a codon ATT to ACT leading to an amino acid substitution of an isoleucine to a threonine at position 179 (I179T).…”

Pigmentation phototype and prostate and breast cancer in a select Spanish population—A Mendelian randomization analysis in the MCC-Spain study

“…Although inflammation, diet, physical inactivity, weight, waist circumference and high body mass index (BMI), play a role as risk factors for PCa[ 6 – 12 ], their link to its etiology remain uncertain and the only well-established risk factors for PCa are family history, ethnicity and age[ 13 – 17 ]. Some genetic variants have also been found to be associated with BC and PCa; for instance, variants in BRCA1 and BRCA2 are strongly associated with BC[ 18 , 19 ], and some genetic scores have been developed for both types of cancer[ 20 , 21 ].…”