Men drink and smoke more than women — but that is not the reason they have a higher cancer risk.
A major study suggests biological differences are the real reason behind the disparity between sexes.
Understanding these differences could help to improve prevention and treatment, researchers say.
The study looked at 300,000 middle-aged and older Americans who did not have cancer over 15 years.
Men were more than twice as likely to develop the disease within the study compared to women - even when lifestyle factors were ruled out.
'This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,' said lead researcher Dr Sarah Jackson, an epidemiologist at the National Cancer Institute.
The observational study did not look at what these differences are.
Scientists have thought men's propensity to enjoy a few more drinks and take more smoke breaks than women was why they had higher rates of cancer in general. But now a major study of 300,000 Americans by the National Cancer Institute suggests biology makes men more vulnerable to cancer, not bad health habits
Some 182,000 women are diagnosed with cancer in the UK every year, rising to 193,000 among men.
In the US, 970,000 men and 928,000 women have cancer confirmed annually.
Researchers from the NCI examined the rates of 21 types of cancers in 171,274 men and 122,826 women.
Participants were aged 50 to 71 and their records were monitored between 1995 and 2011.
The findings, published in the journal CANCER, show 17,951 cancers were detected among men, while just 8,742 were diagnosed among women.
Rates of thyroid and gallbladder cancer were higher among women, but the prevalence of all other cancers were higher among men.
Men were 11-times more likely to develop oesophageal cancer and four times more at risk of stomach or throat cancer.
They also had a three times greater chance of being diagnosed with bladder cancer.
But after accounting for cancer risk factors, such as smoking, alcohol intake and exposure to toxic chemicals, men were still more likely to develop cancer.
Scientists have previously pointed to higher rates of smoking, alcohol consumption and exposure to carcinogens — such as asbestos — due to factory work.
They also said men may be less likely to seek medical advice.
But the results suggest that biological differences between the sexes — such as in physiology, immune system and genes — play a 'major role' in cancer susceptibility.
But scientists have previously found that women have an extra copy of genes that protect against cancer than men.
Study leader Dr Sarah Jackson, an epidemiologist at the National Cancer Institute, said: 'Our results show that there are differences in cancer incidence that are not explained by environmental exposures alone.'
In an editorial accompanying the study, researchers at Washington University called for sex to be taken into account by medics when determining someone's risk of cancer, screening and treatment.
This approach could mitigate and 'may ultimately eradicate' sex disparities in cancer, they said.
WHAT FACTORS INCREASE THE RISK OF DEVELOPING CANCER?
Scientists do not yet know the exact cause of cancer. But a combination of genes, lifestyle and environment can affect the risk of developing it.
For most people, increasing age is the biggest risk factor for developing cancer. In general, people over 65 have the greatest risk of developing cancer. People under 50 have a much lower risk.
Cancer is very common and most people have relatives who have had cancer. People often worry that a history of cancer in their family greatly increases their risk of developing it. But fewer than 1 in 10 cancers are associated with a strong family history of cancer.
In the UK, more than 1 in 4 cancer deaths (over 25 per cent) are caused by smoking.
Breathing in other people’s smoke (passive smoking) also increases your risk of developing cancer.
Drinking alcohol increases your risk of mouth and throat cancers. But it is also linked to other cancers.
In general, the more you drink, the higher your risk. Your risk is even higher if you also smoke.
BEING OVERWEIGHT OR OBESE
Being overweight increases the risk of many types of cancer, including cancers of the bowel, kidney, womb and gullet (oesophagus). Women who are overweight and have been through the menopause also have a higher risk of breast cancer.
Keeping to a healthy body weight reduces your risk of cancer and other health problems, such as heart disease and diabetes.