Are the higher rates of most cancers observed in men primarily caused by biology or lifestyle?
Results from a large, longitudinal US study suggest that underlying biological distinctions between the sexes may be more to blame, rather than any behavioural differences related to smoking or alcohol, and a range of other lifestyle factors.
Researchers from the US National Cancer Institute looked at the risk of 21 cancers among more than 150,000 men and 100,000 women aged 50 – 71 years, who took part in the NIH-AARP’s Diet and Health study, which ran from 1995 – 2011.
They examined the extent to which behaviours (smoking and alcohol use), anthropometrics (body mass index and height), lifestyles (physical activity, diet, medications), and medical history collectively explained the male predominance of risk.
During that time, 17,951 new cancers arose in men and 8,742 in women and the team’s results, published August 8th in the journal Cancer, found that the risks of developing the disease were 1.3- to 10.8-times higher in men than women throughout the body – except for the thyroid and gallbladder.
Lead author and NCI researcher, Professor Sarah Jackson, said that men had an increased risk of most cancers even after adjusting for a wide range of risk behaviours and carcinogenic exposures.
“Indeed, differences in risk behaviours and carcinogenic exposures between the sexes only accounted for a modest proportion of the male predominance of most cancers, ranging from 11% for oesophageal cancer to 50% for lung cancer,” Dr Jackson said.
“Our results show that there are differences in cancer incidence that are not explained by environmental exposures alone, and this suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer.
“Going beyond sex chromosomes and sex hormones, many essential human biologic mechanisms and epigenetics are sex-distinct, constituting the biologic fundamentals for sex disparities in cancer… although to a various extent by cancer site.”
For example, immunotherapy tends to work better in females for non-small cell lung cancer but is more effective in males for colorectal cancer.
“Understanding the reasons for sex differences in cancer risk could provide important information to improve prevention and treatment,” Dr Jackson said, pointing out that a multifaceted approach needs to be developed to address the issue.
Lifestyle and environmental factors still played an important role in determining risk, with the results showing that they explained a significant proportion of the observed male excess for oesophageal adenocarcinoma, as well as cancers of the liver, biliary tract, bladder, skin, colon, rectum, and lungs – ranging from 50% for lung cancer to 11% for throat cancer.
“Yet these risk factors do not stand alone but, rather, interplay intricately while exerting their effects on sex disparities,” Dr Jackson said.
“Strategically, including sex as a biological variable should be enforced along the whole cancer continuum – from risk prediction and cancer primary prevention, cancer screening and secondary prevention, to cancer treatment and patient management.”