Why, oh Y, does smoking put men at more risk?

By Jasminee Sahoye

the loss of the Y chromosome is linked to cancer - researchers
the loss of the Y chromosome is linked to cancer – researchers

Researchers at Uppsala University in Sweden have discovered why smoking could be a greater risk factor for cancer among men and why men generally have a shorter life expectancy than women.

They have found an association between smoking and loss of the Y chromosome in blood cells and that the loss of the Y chromosome is linked to cancer.

The researchers believe that since only men have the Y chromosome, these results might explain why smoking is a greater risk factor for cancer among men and why men in general have a shorter life expectancy.

Epidemiological data show that male smokers have a greater risk of developing cancer outside the respiratory tract than female smokers.

In this recent study, published in Science, which is the result of an international collaboration, the researchers discovered an association between smoking and genetic damage among men that might explain this sex difference.

The study lead researcher at the Department of Immunology, Genetics and Pathology, Uppsala University, Lars Forsberg, says, “We have previously in 2014 demonstrated an association between loss of the Y chromosome in blood and greater risk for cancer. We now tested if there were any lifestyle or clinical factors that could be linked to loss of the Y chromosome.

“Out of a large number of factors that were studied, such as age, blood pressure, diabetes, alcohol intake and smoking, we found that loss of the Y chromosome in a fraction of the blood cells was more common in smokers than in non-smokers.”

He says the association between smoking and loss of the Y chromosome was dose dependent, that is, loss of the Y chromosome was more common in heavy smokers compared to moderate smokers.

The association was only valid for men, who were current smokers.

Men who had been smoking previously, but quit, showed the same frequency of cells with loss of the Y chromosome, as men who had never smoked.

“These results indicate that smoking can cause loss of the Y chromosome and that this process might be reversible. We found that the frequency of cells with loss of the Y chromosome was not different among ex-smokers compared to men who had never smoked. This discovery could be very persuasive for motivating smokers to quit,” says Forsberg.

“How loss of the Y chromosome in blood cells, induced by smoking, is connected with the development of cancer throughout the body is still not clear. One possibility is that immune cells in blood, that have lost their Y chromosome, have a reduced capacity to fight cancer cells.”

Jan Dumanski, one of Forsberg’s colleagues in the same department at Uppsala University, who played a leading role in the study, says, “In summary, we have shown that there is a correlation between a common and avoidable risk factor, that is smoking, and the most common human mutation, loss of the Y chromosome.

“This finding may in part explain why men in general have a shorter life span than women and why smoking is more dangerous for men.”

Meanwhile, in a study earlier this year, the same investigators showed a correlation between a loss of the Y chromosome in blood cells and both a shorter life span and higher mortality from cancer in other organs.

Men have a shorter average lifespan than women and both the incidence and mortality in cancer is higher in men than in women. However, the mechanisms and possible risk factors behind this sex-disparity are largely unknown. Alterations in DNA of normal cells accumulate throughout our lives and have been linked to diseases such as cancer and diabetes.

In the study, published in the journal Nature Genetics, an international team of researchers have analysed the DNA in blood samples from a group of more than 1,600 elderly men. They found the most common genetic alteration was a loss of the Y chromosome in a proportion of the white blood cells.

The group was studied for many years and the researchers could detect a correlation between the loss of the Y chromosome and shorter survival.

The Y chromosome is only present in men and the genes contained on the Y chromosome have so far mostly been associated with sex determination and sperm production.