Familial Cancer: Does Your Sex Make a Difference?

“Modification of familial cancer risk by sex has been rarely studied on a population level”. Photo by Tim Mossholder, Pexels.com

By: Lauri Sipilä and Alison London

(Suomenkielinen teksti)

Can you introduce yourself?

My name is Lauri Sipilä, I’m working on my doctoral thesis in the Tumor Genomics group. I started out in the lab as a research assistant working on data integration, while on the side I was also working on this long ongoing study of cancer clusters in Finland, which had so many facets to it that it spawned my PhD project.

What have you been working on recently?

We have been periodically running analyses on Finnish Cancer Registry‘s data to see if new clusters of cancer patients appeared in the data. In other words, we’re essentially trying to detect whether a given cancer is over-represented somewhere in Finland in some family, when compared to its baseline incidence.

“When it comes to genetics, some Finnish heritage diseases for example have been aggregated in certain areas in Finland”
Photo: Helsinki, Finland by Tapio Haaja from Pexels.com

Does a cancer cluster tell you more about the family itself or suggest something about the place those people live?

It could be either, really, or a combination of the two. When it comes to genetics, some Finnish heritage diseases for example have been aggregated in certain areas in Finland. Finnish people are in general a genetic isolate, but there’s also large regional differences. So the aggregation of cancers in some specific municipality or region could be an indicator of harmful genetic variants enriched in the local populace. But it’s not only about the genes, there’s environmental effects as well: maybe there’s high levels of radon, or an industrial plant that exposes its employees or people in its vicinity to some carcinogenic agent. For example, an Italian study found that the wives of asbestos workers were at a highly increased risk of mesothelioma because the workers brought asbestos home in their work clothes

“It’s not only about genes, there’s environmental effects as well”. Photo: Pexels.com

How do you study these factors?

We wanted to broaden our analysis, so we decided to stratify the data by sex as well. Somewhat surprisingly, the modification of familial cancer risk by sex has been rarely studied on a population level.

Familial Cancer: Does Your Sex Make a Difference? Photo: by Dương Nhân from Pexels.com

Why do you think studies on sex in this type of analysis hasn’t been as widely studied as other variables?

I don’t know for certain. The first answer would be that these analyses are very difficult if not impossible to do in many parts of the world, where registry coverage and quality are not as good as in Finland. The second answer is that if sex modifies familial cancer risk, the effect would likely be quite small. A very broad and general scan like the one we’ve been doing can give an idea of the phenomenon overall, and maybe hints on where to look next. Studies using a more narrow and detailed approach, such as for example focusing only on a certain leukemia, are more common.

What kind of cancers are you looking at?

Pretty much the whole spectrum, excluding sex-specific cancers such as those of the ovaries or prostate. Some rare cancers need to be excluded because of the low number of cases to analyze.

When you added the sex analysis, what did you find out?

The results were of a similar kind as in our normal cancer cluster analysis. There’s a range of excess incidence in families, from slightly elevated risk to really large increases. Population-wide there’s no systematic aggregation bias towards either men or women in any cancer, or at least any bias that we would be able to detect even with data as large as we had.

Were the results surprising? Does this go along with things we know or did you find anything new?

Not really, there’s an older Swedish study analyzing concordant cancer in parents and offspring, which had very similar results. They described a statistically significant sex ratio of familial relative risk in thyroid adenocarcinoma, relative risk being higher in male offspring than female offspring. We didn’t see a similar systematic effect, but there might be something going on based on the individual clusters.

If there are differences in cancers between sex, any evidence to why they might occur?

Well if we forgo the familial aggregation aspect, there’s quite a bit, and some differences can be seen already in pediatric cancers. The most obvious is the association between smoking and lung cancer, smoking habits fluctuating in time in men and women, with changes in cancer incidence.

Association between lung cancer and smoking: Cancer incidences of men and women follow changes in smoking habits. Photo: Pexels.com

What does this mean for further study?

It shows that sex has at best a very limited effect on the familial aggregation of cancer. There may be rare exceptions to this rule, and we can for example study the clusters found in this analysis by accessing the pathology archives of central hospitals in Finland.

You can read the article Sex-specific familial aggregation of cancers in Finland here.

Photo: Lauri Si­pilä, M.Sc., Ph.D. stu­dent from the Tumor Genomics Group with his dog “Maus”. Photo: Lauri Sipilä

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