Are you at risk?

Exact causes of gall bladder cancer are not known. There are several risk factors for GBC that increases the risk of gall bladder cancers.

• Age- Gall bladder cancers are more frequent in older people [4]. In India GBC is more frequently observed above 45 years of age with maximum incidence at 65 years and above [6].

• Gender- Gall bladder cancer shows strong link to female gender [4]. More than half of the total gall bladder cases are in India are observed in women[6].

• Ethnicity- The risk of developing gall bladder cancer differs from one geographic region to another and for different racial groups [9]. Globally, gall bladder cancer is more in India, Pakistan, Eastern Europe, South American countries, East Asia and the lowest in Africa [3]. In India, the risk of developing gall bladder cancer is highest among north and North-east population while it is lowest among South Indians [6,7].

• Gallstones and Chronic Inflammation of Gall bladder- Gallstones are the most common risk factors for gall bladder cancer [10, 11]. Although direct evidence for causal relationship between gallstones and gall bladder cancer is lacking, studies show a significant association between the two [12]. Gallstones are mostly cholesterol, mixed with other substances found in bile and cause chronic inflammation of GB (cholecystitis) [13]. Only about 1% patients with gall stones develop GBC [14]. Long standing inflammation of gall bladder by gallstones leads to the deposition of calcium on the gall bladder wall causing a condition called ‘porcelain gall bladder’ which increases the risk for GBC [11]. Around 25% (range 12% to 61%) of gall bladder cancers were associated with this condition [15]. A study from North India revealed that the prevalence of gallstones was more in females (5.59%) than males (1.99%) [16]. A family history of gallstones doubles risk of gall bladder cancer [1]. However, most people with an inflamed gall bladder or gallstones do not get gall bladder cancer.

• Genetic Factors

(a) Pancreas and bile duct abnormalities- Some congenital abnormalities (present since birth) of the pancreas and bile ducts increase the risk of getting gall bladder cancer [17,8].
(b) Choledochal cysts- Congenital choledochal cysts are bile-filled sacs (dilatations) along the bile duct that are connected to the common bile duct, the tube that carries bile from the liver and gall bladder and empties into the duodenum, a part of the small the intestine [18]. The cells lining these sacs often have areas of pre-cancerous changes, which increase a person’s risk for gall bladder cancer [4].

• Gall bladder polyps- Gall bladder polyp is a growth that develops on the inner surface of the gall bladder wall and may not be cancerous as such. These polyps may be formed either by cholesterol deposits in gall bladder, or may be caused by inflammation [9, 11]. Over a long period of time, a few of these polyps may develop into cancer [19].
  Polypoidal masses of the gall bladder are known to affect around 5% of adults [19]. Cancer risk depends on the size of the polyp; the larger the polyp the greater will be the risk that it will become cancerous. Polyps larger than one centimetre are more likely to be cancerous [9].

• Family History – If there is history of GBC in first degree relatives, a person’s chance of developing gall bladder cancer increases by almost five times [20]. Mutations in certain genes (BRCA2) which increase the risk of familial breast and ovarian cancers have been shown to slightly increase the risk for developing gall bladder and bile duct cancers [21].
  Variants of the APOB gene responsible for apolipoprotein B function, which influences cholesterol handling by the liver, have been associated with an increased risk for gallbladder can­cer; however this is independent of presence of gall stones [22].

• Lifestyle Factors –

(a) Obesity- Being overweight can increase the risk of many types of cancers, including gall bladder cancer [12]. The association of GC with overweight was the second strongest among all cancer sites after that of cancer of the corpus uteri among women and liver cancer among men[12]. Obesity is in fact a risk factor for gallstones, which have a definite association with gall bladder cancer [23]. It has been estimated that one out of ten cases of gall bladder cancer in men and almost a fifth of cases in women are linked with obesity [20].

(b) Infection – Chronic infection with salmonella, the bacterium that cause typhoid, can cause gall bladder inflammation and this can increase the risk of gall bladder cancer in people who have gallstones [24,25]. Approximately 6% of carriers of Salmonella typhi developed gall bladder cancer and the association showed a 12-fold increase in risk for developing GBC [9]. A few studies show that Helicobacter pylori bacteria may also increase the risk of gall bladder cancer [26,27].

(c) Diet – Diet with increased quantities of proteins, fats and cholesterol and low in fibre, vegetables and fruits has been suggested as a risk factor for GBC [14]. Though a few studies from India which also suggest association but lack scientific evidence at a population level,  to prove the definite link between diet and GBC [29].

• Chemicals- Certain chemical compounds like nitrosoamines (found in cigarettes and in some industrial products) may increase the risk of GBC [30].
  Cluster analysis has showed a strong correlation with heavy metal pollutants in drinking water in an endemic population at high risk in specific villages of Vaishali district, Bihar, India [16]. Studies also show that people who smoke or work in the metal or rubber industry are more likely to develop gall bladder cancer than general public [16,30].

If you have one or more risk factors, it does not imply that you will get gall bladder cancer certainly. Many people with more or no exposure to risk factors also get cancer.