Kidney cancer risk factors

Information on risk factors for kidney cancer is presented on this page, including age and sex, tobacco smoking, bodyweight and height, medical conditions and treatment. There is also information on reproductive factors, occupation, genetic syndromes and family history, and previous cancers. Meta-analyses and systematic reviews are cited where available, as they provide the best overview of all available research and most take study quality into account. Individual case-control and cohort studies are reported where such aggregated data are lacking.

Renal cell carcinoma (RCC) accounts for the majority of kidney cancers diagnosed in UK adults and will be the main focus of this page, except where specified otherwise.

The major risk factors for kidney cancer include age, sex, obesity, smoking, and some genetic and medical conditions. Smoking and obesity are both preventable causes. In Britain smoking has declined in both men and women while the proportion of the population who are obese or overweight has risen.1,2  So although there may be a reduction in smoking-related kidney cancers there is likely to be a rise in obesity-related cases.

A study published in December 2011 estimated that around 42% of kidney cancer cases in the UK are due to smoking and excess bodyweight. The proportion is higher in men (47%) than women (34%), reflecting that, in the past, men were more likely than women to smoke.3

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Kidney cancer risk factors

 

Factors shown to increase kidney cancer risk

 
 

Age and male gender 

The risk of kidney cancer increases with age: around three-quarters of all cases occur in men and women over the age of 60. The disease is more common in men than in women - there are three male cases for every two female cases.

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Tobacco smoking 

The International Agency for Research on Cancer (IARC) states that kidney, renal pelvis and ureter cancers are all caused by tobacco smoking.4

On average, current smokers have a 50% increase in risk of kidney cancer.5 Risk increases with the number of cigarettes smoked per day. People who smoke more than 20 cigarettes per day increase their risk by 60-100% compared to people who have never smoked.6

Kidney cancer risk declines after smoking cessation. As a group, former smokers have a 25% higher risk of kidney cancer.5 Those who quit ten or more years previously have a similar risk to lifelong never-smokers.6 Risk for cancer of the renal pelvis is increased by more than three-fold in current smokers,7,8 and even higher risk increases have been shown for cancers of the ureter.8

A study published in December 2011 estimated that more than 29% of kidney cancer cases (including the renal pelvis and ureter) in men and around 15% in women in the UK in 2010 were caused by smoking.9

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Bodyweight and height

Obesity is an established risk factor for kidney cancer in both men and women. Risk increases by 24% in men and 34% in women for every additional 5 points in body mass index (BMI).10 A study published in December 2011 estimated that about 25% of kidney cancer cases in men and 22% in women in the UK in 2010 were linked to being overweight.11

The mechanisms proposed to explain the strong association with excess bodyweight include raised levels of insulin, oestrogens and growth factors, and changes in cholesterol metabolism or the immune system.12

According to the Million Women Study, risk of kidney cancer increases by 29% per 10cm increase in height.13 Previous evidence for a relationship of height and kidney cancer risk was inconsistent.14

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Medical conditions and treatment 

Hypertension (high blood pressure)

The kidneys play a vital role in controlling blood pressure by regulating extracellular fluid (the fluid in the body lying outside the cells). When arterial pressure is high, the kidneys increase the rate at which both water and sodium are excreted. This in turn, results in less extracellular fluid and a decrease in blood pressure.

According to a meta-analysis, kidney cancer risk increases by around 60% in those with a history of hypertension (high blood pressure).15 There is a trend of increasing risk with progressively higher diastolic and systolic blood pressure.7,16 Risk of kidney cancer falls if hypertension is reduced.7

Analyses excluding kidney cancer cases diagnosed within the first few years of follow-up for hypertension also show an increased risk of kidney cancer, arguing against the theory that the risk increase is a result of kidney cancers being more likely to be detected in those with hypertension, or that raised blood pressure is a result of early stage kidney cancer.16 Hypertension may cause damage to the kidney directly, or increase susceptibility to carcinogens.17 A US study estimated that 24% of renal cell carcinoma cases in women and 15% in men are linked to hypertension.18

Some studies have shown an increased risk with use of diuretics and other anti-hypertensive medication, although it is not possible to say whether the effects are independent of hypertension.18-21 Recent evidence mainly indicates that anti-hypertensive medication does not increase kidney cancer risk once the hypertension is brought under control.16,19

Other medications

Phenacetin, an analgesic banned in the UK since 1980, increases the risk of renal pelvis cancer although its effect on renal cell carcinoma is less certain.4

A US study showed that use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) regularly for more than ten years was linked to an almost three-fold risk increase for renal cell carcinoma.22 A Danish study also showed a significant doubling in kidney cancer risk for those with up to nine previous NSAID prescriptions.23

Aristolochic acid, a derivative of the plant Aristolochia, is classified as a cause of cancer of the renal pelvis and ureter by IARC.4 The herb, which is used in some traditional Chinese medicines, can cause damage to the tissues of the renal pelvis and ureter (aristolochic acid nephropathy), which progresses to cancer in about 50% of cases.24 Products containing the herb were the subject of a consumer warning by the Medicines and Healthcare Products Regulatory Agency in 2007.

Other kidney conditions

Acquired cystic kidney disease, which develops in association with long term kidney problems, is common in dialysis patients, and increases the risk of kidney cancer.28,29 Individuals receiving dialysis have a three- to four-fold increased risk of kidney cancer overall, and this risk increases with the number of years on dialysis – it is almost seven-fold higher in patients on dialysis for ten years or more. This risk increase can be attributed to the underlying kidney disease.30,31

Evidence of an effect of kidney stones remains mixed. A cohort study showed a 150% risk increase for cancers of the renal pelvis or ureter in people hospitalised for kidney or ureter stones. Risk remained higher for more than ten years after the stones, arguing against a role of detection bias (increased likelihood of detecting a cancer during medical treatment for another condition). The tumours mainly occurred on the same side as the stone, and it was hypothesised that chronic irritation and infections related to the stone were the cause of the increased cancer risk.32 However, an earlier case-control study showed no risk increase for cancers of the renal pelvis and ureter in people with a history of kidney stones.33 No increased risk was shown for renal cell carcinoma in the cohort study, in contrast to some earlier case-control studies.32 Evidence for a role of urinary tract infections also remains mixed.34-37

Other treatment and medical conditions

Gamma radiation and X radiation are classified as a cause of kidney cancer by IARC.4 The kidney may receive radiation during radiotherapy for testicular cancer, and the risk of kidney cancer is increased approximately two-fold in men with a previous testicular cancer.25 Risk increases with time since the first cancer, rising to three-fold after thirty years or more.26 Radiotherapy for cervical cancer increases the risk of renal cancer by 30% and again, risk continues to increase with time since treatment, reaching almost two-fold for women who have survived for at least 30 years.27

A history of gallstones was associated with a 57% increase in the risk of kidney cancer in a recent case-control study, although previous studies did not show a link.38

An increased risk of kidney cancer in people with diabetes mellitus has been shown in a meta-analysis, although the association was weakened and borderline significant in a subset of studies that adjusted for BMI.39

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Reproductive and intra-uterine factors 

There is evidence of an increased risk of kidney cancer with increasing number of births.40-45 While some early studies pointed to confounding by BMI as an explanation for this association, recent evidence supports an increased risk with higher number of births after adjustment for BMI (75% risk increase for four children compared with one-two).40 There is some evidence for an increased risk after hysterectomy.44-47 It has been hypothesised that this is due to changes in the ureter following the procedure.46 However, not all studies showing an association adjusted for BMI, and a recent cohort study that included this factor in the analysis did not show an association.40 One cohort study showed no association with either number of births or hysterectomy, and more research is needed in this area.48

Having a high birth-weight or being born pre-term birth have been linked to an increased risk of Wilm’s tumour.49

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Occupation 

IARC states that there is limited evidence that exposure to arsenic and cadmium or printing processes can cause kidney cancer.4 Although trichloroethylene has been the subject of a number of studies in relation to kidney cancer, and the most recent meta-analysis showed around a 40% risk increase for occupational exposure,50 IARC does not classify trichloroethylene to be a risk factor for kidney cancer.4

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Genetic syndromes, family history and previous cancers 

Genetic syndromes

Kidney cancer is a feature of several genetic syndromes. 

  • Von Hippel Lindau disease

The risk of someone with von Hippel Lindau disease developing clear-cell RCC increases with age, reaching 70% by age 60.51

  • Hereditary papillary renal cell carcinoma (HPRCC) 

HPRCC is characterised by occurrence of type 1 papillary RCC as well as tumours in other organs.52

  • Hereditary leiomyomatosis renal cell cancer (HLRCC)

Individuals with HLRCC develop benign skin and uterine leiomyomas and, in some cases, highly aggressive type-2 papillary RCC.53

  • Birt-Hogg-Dubé (BHD) syndrome

BHD syndrome is characterised by an increased risk of a number of different types of renal cancer.54

Family history

The syndromes described above are rare, and it is thought that most of the familial risk for kidney cancer is not linked to them, but rather to more common genes with a smaller impact on risk.55 A meta-analysis reported a doubling in risk of renal cell carcinoma in people with a first-degree relative diagnosed with kidney cancer. The risk was approximately four times higher when the affected first-degree relative was a sibling.55

A family history of prostate cancer in a parent or sibling, or melanoma, non-Hodgkin lymphoma, bladder or thyroid cancer in a sibling has also been linked to an increased risk.56

Previous thyroid cancer

People with a previous thyroid cancer have between two and seven times increased risk of kidney cancer.57-59 This may be due to genetic features common to both cancers.60

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Factors shown to have no effect on kidney cancer risk

Aspirin and paracetamol

Aspirin use was not been linked to risk in a meta-analysis,61 and more than one subsequent study.22,62 Paracetamol has also not been linked to risk in more than one study.22,63

Hepatitis C

Individuals infected with hepatitis C have been shown to be at no increased risk of RCC in a large recent study,65 and IARC does not classify hepatitis C infection as a cause of kidney cancer.4 However, one previous study did report an association.64

Alcohol

The World Cancer Research Fund in its 2007 report Food, Nutrition, Physical Activity and the Prevention of Cancer stated that the evidence indicates that alcohol does not have a substantial adverse effect on kidney cancer risk, and that evidence was inadequate to be able to say whether it has a protective effect.66 According to a pooled analysis published in the same year, people drinking more than 15g/day of alcohol (one unit, equivalent to a small glass of wine or half a pint of normal strength beer, contains 8g of alcohol) may have a 30% reduced risk of kidney cancer.67 However, alcohol consumption is known to increase risk of several other cancer types, including breast and bowel.

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Kidney cancer survival statistics

References for kidney cancer risk factors

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