Gender differences in lung cancer: Causes, risk factors, and outcomes

Globally, lung cancer is the second most common cancer diagnosis and the leading cause of cancer-related deaths. The most common symptoms of lung cancer include a chronic cough, coughing up blood, respiratory distress, and weight loss. However, often the symptoms can be less obvious, such as generalized fatigue. Those with more advanced lung cancer may present with complaints of headaches, indicating a spread to the brain, and bone pain or backache, indicating bone metastases. Nearly half of all lung cancer patients will have distant metastases at the time of presentation, indicating stage IV disease.

While smoking is the most significant causative factor associated with lung cancer among Indian males, the association is not as strong among Indian females. Both indoor and outdoor pollution are considered to be more important causes among women, including indoor cooking fumes and second-hand smoke. Adding to the fumes from the fuels used, cooking oils also release carcinogenic polycyclic aromatic hydrocarbons (PAHs) when heated, and the exposure is increased when cooking in poorly ventilated rooms.

Overall, lung cancer is more common among men than women. In India, lung cancer is the most common cancer among males and the fourth most common among females, with a cumulative risk of 1 in 68 males and 1 in 201 females developing lung cancer, respectively. Many lung cancer studies have revealed differences in the causes, risk factors, types of cancer, and eventual outcomes between men and women. Some studies have shown that women are more susceptible to the effects of carcinogens present in tobacco and cigarette smoke. Women are also more likely to be diagnosed with adenocarcinoma than other forms of lung cancer, while squamous cell carcinoma of the lung is rarer in women. Women with lung cancer also tend to be diagnosed at a younger age and lower stage than men, with "stage" indicating how far the cancer has spread within the body. Women diagnosed with lung cancer also tend to have better treatment outcomes than men, especially those with adenocarcinoma of the lung.

For example, in a study from AIIMS, Delhi, published this year, which compared lung cancer in men and women, female patients were usually younger (median age 56 vs. 60 years), and a much smaller proportion of female patients were smokers (29.1% vs. 84.9%). Female patients were also more likely to have adenocarcinoma (54% vs. 30%) and usually survived longer than males (median overall survival of 13.8 vs. 9.1 months). Female patients were also more likely to have EGFR mutations, making them eligible for targeted therapies against the EGFR mutations.

While a few western studies have shown that women aged 30-49 years are more likely to develop lung cancer than males of the same age group, this has not been definitively shown in the Indian population. The reasons for the increased incidence in young western women are still unclear, although they have been variously attributed to a greater sensitivity to cancer-causing chemicals (especially those found in cigarette smoke) among women and a decreased ability to repair DNA damage in females. Some researchers point to the increased levels of estrogen among pre-menopausal females, which may promote carcinogenesis, and an increased expression of estrogen receptors in lung cancer. Cancer-driving mutations such as EGFR are also more common in this population.

(Dr Azgar Abdul Rasheed is a Consultant, Department of Medical Oncology, KIMSHEALTH Cancer Centre)