Prostate cancer (male)

Prostate cancer is among the most common cancers in men. This score sums many common variants that shift lifetime risk (relevant to people with a prostate).

What this prostate cancer score reads

This is PGS000662, the 269-variant score from Conti and colleagues' 2021 trans-ancestry meta-analysis in Nature Genetics, built on GWAS data from 234,253 men across European, African, East Asian and Hispanic ancestry groups and fine-mapped to pick independent signals.

It is the best-validated score on this site by some distance, and the one with the most published evidence behind it.

How well it predicts prostate cancer

In 199,969 men of European ancestry (6,852 with prostate cancer), men in the top 10% of the score had 4.17 times the odds of prostate cancer compared with men in the middle of the distribution. A model combining the score with age and ancestry components reached an area under the curve of 0.833, though age carries a large part of that.

It was also tested outside European ancestry, which is rare. In men of African ancestry the top 10% carried 3.53 times the odds against the middle, with an area under the curve of 0.679, and a separate African American cohort showed roughly twice the risk in the top group.

The limitation that matters most here

Prostate cancer is unusual in that many cases never threaten life, while a minority are aggressive. A useful score would ideally flag the second kind, and this one largely does not.

In African-ancestry validation, the score's discrimination for aggressive disease was close to chance: an area under the curve of 0.505 for tumour stage T4 and 0.523 for Gleason score 8 or above, against 0.579 for prostate cancer overall in the same men. Read plainly, the score is better at predicting who receives a diagnosis than who has dangerous disease, and screening harms come mostly from diagnosing the harmless kind.

What this score does not capture

Rare high-risk variants in BRCA2 and HOXB13 raise prostate cancer risk substantially, are relevant to treatment as well as screening, and are not read by a consumer chip or included here. A strong family history of prostate, breast, ovarian or pancreatic cancer is a reason to raise inherited cancer risk with a doctor whatever a polygenic score says.

Age and family history remain the dominant risk factors, and PSA screening decisions are made on guidelines and individual discussion, not on percentiles.

Ancestry and accuracy

Men of African ancestry have roughly double the prostate cancer incidence of men of European ancestry, and that difference is not explained by this score: the score ranks men within a population rather than between populations. Its own validation showed weaker discrimination in African-ancestry men (0.679 against 0.833 with the same covariates), which is the usual portability gap even for a score built with trans-ancestry data.

Variants in this score you can read on their own

This score includes a variant that this site also explains individually, where you can see what each genotype means on its own: Colorectal cancer risk (8q24) (rs6983267).

How much of this score your file covers

249 of the published score's 269 variants are present in a standard consumer DNA file (93%). The remaining 20 cannot be read from one, so a result computed here approximates the published score rather than reproducing it.

Common questions

Should I start PSA testing because of a high polygenic score? That is a discussion to have with a doctor, weighing your age, family history and views on the trade-offs of screening. The evidence gap matters here: this score predicts diagnosis better than it predicts aggressive disease, and the main harm of screening is finding cancers that would never have caused trouble.

Does this score cover BRCA2? No. BRCA2 and HOXB13 carry rare, large-effect variants that a common-variant score does not read and a consumer genotyping chip does not reliably detect. Those need clinical genetic testing, usually prompted by family history.

Why is my score high when nobody in my family had prostate cancer? The two are partly independent. A polygenic score sums many common variants that can be inherited without producing an obvious family pattern, while family history also carries rare variants and shared environment the score cannot see. Neither replaces the other.

Related

APOE type (Alzheimer's & cholesterol) · Atrial fibrillation · Coronary artery disease · Depression · Fasting glucose / type 2 diabetes (MTNR1B) · Prothrombin clotting variant · Type 2 diabetes protection (PPARG Pro12Ala)